CINXE.COM

<!DOCTYPE html><html lang="en"><head><meta charSet="utf-8"/><meta name="viewport" content="width=device-width, initial-scale=1"/><link rel="preload" as="image" href="/_next/static/media/logo-bmj-journals.c2a2899be06382c530c7bc1e5d61e633.svg" /><link rel="preload" as="image" href="/next-resources/logo.svg" /><link rel="preload" as="image" href="/next-resources/search.svg" /><link rel="preload" as="image" href="/next-resources/hamburger-menu.svg" /><link rel="preload" as="image" href="https://resources.bmj.com/repository/journals-network-project/images/social-media/rss.svg" /><link rel="preload" as="image" href="https://resources.bmj.com/repository/journals-network-project/images/social-media/x.svg" /><link rel="preload" as="image" href="/_next/static/media/bmj-footer-logo.c6e1ad28003cb22dbd978555514ed05c.svg" /><link rel="preload" as="image" href="/next-resources/publication-details.svg" /><link rel="preload" as="image" href="/next-resources/open-access.svg" /><link rel="preload" as="image" href="/next-resources/vector.svg" /><link rel="stylesheet" href="/_next/static/css/bb076035c270e51f.css" data-precedence="next" /><link rel="stylesheet" href="/_next/static/css/c9c0e70a6968a49d.css" data-precedence="next" /><link rel="stylesheet" href="/_next/static/css/66ad511738c93f8a.css" data-precedence="next" /><link rel="preload" as="script" fetchPriority="low" href="/_next/static/chunks/webpack-8279bfe1e5fb5dfc.js" /><script src="/_next/static/chunks/1dd3208c-7f75999651337873.js" async=""></script><script src="/_next/static/chunks/286-b7674269bd0f8848.js" async=""></script><script src="/_next/static/chunks/main-app-5d89451faab8abb1.js" async=""></script><script src="/_next/static/chunks/9af238c7-693cab6698f4b9fe.js" async=""></script><script src="/_next/static/chunks/22747d63-441d638379b6d561.js" async=""></script><script src="/_next/static/chunks/352-9002e424cdc49415.js" async=""></script><script src="/_next/static/chunks/789-d2923bae8cb39657.js" async=""></script><script src="/_next/static/chunks/809-5ff6e64efd158e65.js" async=""></script><script src="/_next/static/chunks/21-54856eee41e993bd.js" async=""></script><script src="/_next/static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js" async=""></script><script src="/_next/static/chunks/619-a89c76242bbf01ff.js" async=""></script><script src="/_next/static/chunks/app/error-7bbbe3d22319187d.js" async=""></script><link rel="preload" href="https://securepubads.g.doubleclick.net/tag/js/gpt.js" as="script" /><link rel="preload" href="https://cookie-cdn.cookiepro.com/scripttemplates/otSDKStub.js" as="script" /><link rel="preload" as="image" href="/next-resources/download-pdf.svg" /><link rel="preload" as="image" href="https://orcid.org/sites/default/files/images/orcid_16x16.png" /><link rel="preload" as="image" href="/next-resources/mail.svg" /><link rel="preload" as="image" href="/next-resources/tooltip.svg" /><link rel="preload" as="image" href="/content/svnbmj/7/6/527/F1.medium.gif" /><link rel="preload" as="image" href="/content/svnbmj/7/6/527/F2.medium.gif" /><link rel="preload" as="image" href="/content/svnbmj/7/6/527/F3.medium.gif" /><link rel="preload" as="image" href="/content/svnbmj/7/6/527/F4.medium.gif" /><link rel="preload" as="image" href="/next-resources/AccordionArrowDown.svg" /><link rel="preload" as="image" href="/next-resources/circle-arrow-up.svg" /><link rel="preload" as="image" href="/next-resources/open-url-for-metrics.svg" /><link rel="shortcut icon" href="/next-resources/favicon.ico" type="image/vnd.microsoft.icon" /><link rel="preload" href="https://securepubads.g.doubleclick.net/tag/js/gpt.js" as="script" /><link rel="preconnect dns-prefetch" href="https://analytics.bmj.com" /><link rel="preconnect dns-prefetch" href="https://securepubads.g.doubleclick.net" /><link rel="preconnect dns-prefetch" href="https://cdn-eu.pagesense.io" /><link rel="preconnect dns-prefetch" href="https://popup.wisepops.com" /><link rel="preconnect dns-prefetch" href="https://www.medtargetsystem.com" /><link rel="preload" href="https://cookie-cdn.cookiepro.com/scripttemplates/otSDKStub.js" as="script" /><title>Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice | Stroke and Vascular Neurology</title><meta name="description" content="Background Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.Methods Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.Results These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p<0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p<0.05) and caused acute instead of prolonged impairment of spatial reference memory (p<0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p<0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p>0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p<0.05).Conclusion We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI."/><meta name="DC.Contributor" content="Zhiyuan Zhou"/><meta name="DC.Contributor" content="Yuanyuan Ma"/><meta name="DC.Contributor" content="Tongtong Xu"/><meta name="DC.Contributor" content="Shengju Wu"/><meta name="DC.Contributor" content="Guo-Yuan Yang"/><meta name="DC.Contributor" content="Jing Ding"/><meta name="DC.Contributor" content="Xin Wang"/><meta name="DC.Format" content="text/html"/><meta name="DC.Identifier" content="10.1136/svn-2022-001594"/><meta name="DC.Language" content="en"/><meta name="DC.Publisher" content="BMJ Publishing Group Ltd"/><meta name="DC.AccessRights" content="open-access"/><meta name="DC.Title" content="Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice"/><meta name="DC.Description" content="Background Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.Methods Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.Results These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p<0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p<0.05) and caused acute instead of prolonged impairment of spatial reference memory (p<0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p<0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p>0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p<0.05).Conclusion We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI."/><meta name="DC.Date" content="2022-12-20"/><meta name="DC.Type" content="journal-article"/><meta name="DC.Rights" content="This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license"/><meta name="citation_title" content="Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice"/><meta name="citation_abstract" content="Background Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.Methods Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.Results These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p<0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p<0.05) and caused acute instead of prolonged impairment of spatial reference memory (p<0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p<0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p>0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p<0.05).Conclusion We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI."/><meta name="citation_journal_title" content="Stroke and Vascular Neurology"/><meta name="citation_publisher" content="BMJ Publishing Group Ltd"/><meta name="citation_publication_date" content="2022-12-20"/><meta name="citation_volume" content="7"/><meta name="citation_issue" content="6"/><meta name="citation_doi" content="10.1136/svn-2022-001594"/><meta name="citation_mjid" content="svnbmj;7/6/null"/><meta name="citation_id" content="7/6/null"/><meta name="citation_public_url" content="https://svn.bmj.com/content/7/6/527"/><meta name="citation_full_html_url" content="https://svn.bmj.com/content/7/6/527"/><meta name="citation_pdf_url" content="https://svn.bmj.com/content/7/6/527.full.pdf"/><meta name="citation_issn" content="2059-8696"/><meta name="citation_journal_abbrev" content="Stroke Vasc Neurol"/><meta name="citation_pmid" content="10.1136/svn-2022-001594"/><meta name="citation_article_type" content="research-article"/><meta name="citation_section" content="Original research"/><meta name="citation_access" content="open-access"/><link rel="canonical" href="/content/7/6/527" /><link rel="alternate" type="application/pdf" href="/content/7/6/527.full.pdf" /><meta property="og:title" content="Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice"/><meta property="og:description" content="Background Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.Methods Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.Results These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p<0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p<0.05) and caused acute instead of prolonged impairment of spatial reference memory (p<0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p<0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p>0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p<0.05).Conclusion We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI."/><meta property="og:url" content="https://svn.bmj.com/content/7/6/527"/><meta property="og:site_name" content="Stroke and Vascular Neurology"/><meta property="og:locale" content="en_GB"/><meta property="og:image" content="https://svn.bmj.com/content/svnbmj/7/6/527/F1.medium.gif"/><meta property="og:image:width" content="800"/><meta property="og:image:height" content="600"/><meta property="og:image:alt" content="Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice"/><meta property="og:image" content="https://svn.bmj.com/content/svnbmj/7/6/527/F1.large.jpg"/><meta property="og:image:width" content="1800"/><meta property="og:image:height" content="1600"/><meta property="og:image:alt" content="Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice"/><meta property="og:type" content="website"/><meta name="twitter:card" content="summary_large_image"/><meta name="twitter:site" content="@bmj_latest"/><meta name="twitter:title" content="Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice"/><meta name="twitter:description" content="Background Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.Methods Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.Results These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p<0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p<0.05) and caused acute instead of prolonged impairment of spatial reference memory (p<0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p<0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p>0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p<0.05).Conclusion We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI."/><meta name="twitter:image" content="https://svn.bmj.com/content/svnbmj/7/6/527/F1.medium.gif"/><meta name="twitter:image:alt" content="Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice"/><meta name="citation_author"/><meta name="citation_author_institution"/><script src="/_next/static/chunks/polyfills-78c92fac7aa8fdd8.js" noModule=""></script><script> window.dataLayer = window.dataLayer || []; function parseCookies() { let cookieHeader = document.cookie || ""; let cookies = Object.fromEntries( cookieHeader.split("; ").map((c) => c.split("=")) ); for (let key in cookies) { if (cookies[key] === "undefined") { cookies[key] = undefined; } } return cookies; } function uuidv4() { var d = new Date().getTime(); //Timestamp var d2 = (typeof performance !== "undefined" && performance.now && performance.now() * 1000) || 0; //Time in microseconds since page-load or 0 if unsupported return "xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx".replace(/[xy]/g, function (c) { var r = Math.random() * 16; //random number between 0 and 16 if (d > 0) { //Use timestamp until depleted r = (d + r) % 16 | 0; d = Math.floor(d / 16); } else { //Use microseconds since page-load if supported r = (d2 + r) % 16 | 0; d2 = Math.floor(d2 / 16); } return (c === "x" ? r : (r & 0x3) | 0x8).toString(16); }); } function handleCookie() { let cookies = parseCookies(); let bmj_uuid = cookies.bmj_uuid; if (!bmj_uuid) { bmj_uuid = uuidv4(); cookies.bmj_uuid = bmj_uuid; } return { bmj_uuid }; } let { bmj_uuid } = handleCookie(); let bmj_ppid = parseCookies().bmj_ppid; const anonMailId = "e3b0c44298fc1c149afbf4c8996fb92427ae41e4649b934ca495991b7852b855"; let nonAnonMailId = window.dataLayer.find((item) => item.user)?.user?.mail === anonMailId ? null : window.dataLayer.find((item) => item.user)?.user?.mail; let userId = dataLayer.find((item) => item.user)?.user?.["data-ics"] ?? (dataLayer.find((item) => item.user)?.user?.mail && nonAnonMailId) ?? bmj_ppid ?? bmj_uuid; document.cookie = "bmj_ppid=" + userId + "; domain=.bmj.com; path=/; max-age=31622400; SameSite=None; Secure"; document.cookie = "bmj_uuid=" + bmj_uuid + "; domain=.bmj.com; path=/; max-age=31622400; SameSite=None; Secure"; var googletag = googletag || { cmd: [] }; googletag.cmd.push(function () { googletag.pubads().setPublisherProvidedId(userId); googletag.enableServices(); }); window.dataLayer.push({ bmj_uuid: bmj_uuid, }); </script> </head><body><div><div class="border-b-bmj-silver-100 bg-bmj-siver-30 border-b flex items-center justify-center py-3 min-w-[auto] min-h-[100px] md:min-h-[250px]"><div id="div-gpt-ad-3321227-1" data-testid="top-ad-slot" class="flex items-center justify-center w-[auto] h-[100px] md:h-[250px]"></div></div><header class="hidden flex-wrap items-center justify-between px-4 md:flex md:flex-nowrap" data-testid="header-panel"><a href="https://journals.bmj.com" class="py-2 px-0 flex items-center"><img class="h-[42px] w-[154px]" data-testid="bmj-journals-logo" src="/_next/static/media/logo-bmj-journals.c2a2899be06382c530c7bc1e5d61e633.svg" alt="BMJ Journals logo" /></a><nav class="flex flex-wrap items-center justify-between md:flex-nowrap"><div data-testid="search-box" class="flex w-72 flex-col bg-white/20 p-2 pr-4 md:w-[343px] md:flex-row md:items-start md:p-0 md:pr-0 undefined"><form role="search" class="flex undefined" action="/search" method="post"><input type="textbox" placeholder="search" title="Search for:" class="border-bmj-silver-100 rounded-0 h-[34px] w-[207px] appearance-none border p-[5px] pl-[10px] align-middle text-[14px] undefined" name="keywords"/><button type="submit" class="bg-bmj-siver-30 border-bmj-silver-100 rounded-0 ml-[-4px] h-[34px] appearance-none border py-[1px] pl-[10px] pr-[12px] text-[13.33px] undefined" name="op">Search</button><input type="hidden" name="form_id" value="highwire_search_quicksearch_form_1"/></form><div class="flex justify-start pl-[5px] pt-[3px] text-left md:justify-end undefined"><a href="/search" title="Advanced Search" class="decoration-none lg:text-bmj-blue-500 mt-2 flex flex-row text-[12.75px] leading-[normal] md:mt-0 md:flex-col [&>:first-of-type]:mr-1 undefined"><span>Advanced</span><span>search</span></a></div></div></nav></header><div data-testid="page-with-menu" class=" transition-margin-left relative m-0 mx-auto min-h-[512px] w-full min-w-0 duration-300 [&.panel-enter-active]:ml-[-15.625rem] [&.panel-enter-done]:ml-[-15.625rem] [&.panel-enter]:ml-0 [&.panel-exit-active]:ml-0 [&.panel-exit-done]:ml-0 [&.panel-exit]:ml-[-15.625rem]"><div class=""><div data-testid="top-menu-container" role="presentation" class="bg-bmj-primary-brand mx-auto h-[3.5625rem] w-full min-w-0 md:h-[4.375rem]"><nav role="navigation" class="relative m-0 mx-auto flex h-full w-full min-w-0 justify-between pl-4 pr-0"><div class="w-1/2 md:w-1/5 bg-bmj-primary-brand m-0 flex min-w-0 items-center"><a href="/" class="flex h-full w-full items-center"><img data-testid="top-menu-logo" src="/next-resources/logo.svg" alt="logo" class="h-auto w-full" /></a></div><div class=" bg-bmj-primary-brand m-0 flex min-w-0 items-center"><div class="hidden h-full lg:flex"><a class="decoration-none text-4.25 rounded-0 text-bmj-white [&:hover]:md:bg-bmj-white/20 flex h-full cursor-pointer items-center whitespace-nowrap border-0 bg-transparent px-2 py-4 font-sans leading-5 [&:focus-visible]:outline-none [&:hover]:bg-transparent [&:last-child]:pr-4 [&.is-active]:bg-white/20" href="/content/early/recent" data-testid="354">Latest content</a><a class="decoration-none text-4.25 rounded-0 text-bmj-white [&:hover]:md:bg-bmj-white/20 flex h-full cursor-pointer items-center whitespace-nowrap border-0 bg-transparent px-2 py-4 font-sans leading-5 [&:focus-visible]:outline-none [&:hover]:bg-transparent [&:last-child]:pr-4 [&.is-active]:bg-white/20" href="/content/current" data-testid="355">Current issue</a><a class="decoration-none text-4.25 rounded-0 text-bmj-white [&:hover]:md:bg-bmj-white/20 flex h-full cursor-pointer items-center whitespace-nowrap border-0 bg-transparent px-2 py-4 font-sans leading-5 [&:focus-visible]:outline-none [&:hover]:bg-transparent [&:last-child]:pr-4 [&.is-active]:bg-white/20" href="/content/by/year" data-testid="356">Archive</a><a class="decoration-none text-4.25 rounded-0 text-bmj-white [&:hover]:md:bg-bmj-white/20 flex h-full cursor-pointer items-center whitespace-nowrap border-0 bg-transparent px-2 py-4 font-sans leading-5 [&:focus-visible]:outline-none [&:hover]:bg-transparent [&:last-child]:pr-4 [&.is-active]:bg-white/20" href="/pages/authors/" data-testid="357">For authors</a><a class="decoration-none text-4.25 rounded-0 text-bmj-white [&:hover]:md:bg-bmj-white/20 flex h-full cursor-pointer items-center whitespace-nowrap border-0 bg-transparent px-2 py-4 font-sans leading-5 [&:focus-visible]:outline-none [&:hover]:bg-transparent [&:last-child]:pr-4 [&.is-active]:bg-white/20" href="/pages/about/" data-testid="358">About</a></div><div class="flex h-full lg:hidden"><button class=" md:hidden decoration-none text-background rounded-0 flex h-full cursor-pointer items-center whitespace-nowrap border-none bg-transparent px-2 py-4 font-sans leading-5 text-[4.25] [&:focus-visible]:outline-0 [&:hover]:bg-transparent [&:hover]:md:bg-white/20 [&:last-child]:pr-4"><img src="/next-resources/search.svg" alt="Search" width="36" height="36" /></button><button class=" decoration-none text-background rounded-0 flex h-full cursor-pointer items-center whitespace-nowrap border-none bg-transparent px-2 py-4 font-sans leading-5 text-[4.25] [&:focus-visible]:outline-0 [&:hover]:bg-transparent [&:hover]:md:bg-white/20 [&:last-child]:pr-4"><img src="/next-resources/hamburger-menu.svg" alt="Menu" width="36" height="36" /></button></div></div></nav></div><main><div><div><div class="navbar transform-translate-y-full top-[8rem] opacity-0 bg-bmj-white/30 fixed z-10 w-full backdrop-blur-md transition-transform duration-300 ease-in-out"><div class="progress-bar bg-bmj-blue-600 block h-[2px]" style="width:0%"></div></div><div class="bg-white"><div class="flex justify-between bg-white pt-2 md:mb-10 mb-[24px]"><div><div data-testid="breadcrumbs" class="px-4"><span class="text-bmj-font-color-medium text-sm font-normal not-italic leading-4" data-testid="ancestor-wrapper"><a class="decoration-none text-bmj-blue-600 hover:text-bmj-blue-700 text-sm font-normal no-underline" data-testid="home" href="/">Home</a></span><span class="text-bmj-grey-breadcrumb m-2 text-sm">/</span><span class="text-bmj-font-color-medium text-sm font-normal not-italic leading-4" data-testid="ancestor-wrapper"><a class="decoration-none text-bmj-blue-600 hover:text-bmj-blue-700 text-sm font-normal no-underline" data-testid="archive" href="/content/by/year">Archive</a></span><span class="text-bmj-grey-breadcrumb m-2 text-sm">/</span><span class="text-bmj-font-color-medium text-sm font-normal not-italic leading-4" data-testid="ancestor-wrapper"><a class="decoration-none text-bmj-blue-600 hover:text-bmj-blue-700 text-sm font-normal no-underline" data-testid="volume 7, issue 6" href="/content/7/6">Volume 7, Issue 6</a></span></div></div><a href="https://myaccount.bmj.com/myaccount/signup.html?regService=etoc-alerts&corpusCode=svnbmj&fwdUrl=https://svn.bmj.com" class="undefined text-bmj-blue-600 [&:hover]:text-bmj-blue-700 hidden no-underline md:inline-block"><div class="flex"><div class="mr-2 flex"><svg class="text-bmj-primary-brand h-4 w-8" data-testid="envelope-icon" viewBox="0 0 33 22" fill="none" xmlns="http://www.w3.org/2000/svg"><path d="M1 1H32V21H1V1Z" fill="white" stroke="currentColor"></path><path d="M31.9 20.8L21 9" stroke="currentColor"></path><path d="M1 20.5L11.8 9" stroke="currentColor"></path><mask id="path-4-inside-1" fill="white"><path d="M0.600098 0.700012L16.6001 13.4L32.4001 0.900012"></path></mask><path d="M16.6001 13.4L15.9784 14.1833L16.5991 14.6759L17.2205 14.1843L16.6001 13.4ZM-0.0216079 1.48326L15.9784 14.1833L17.2218 12.6168L1.2218 -0.0832389L-0.0216079 1.48326ZM17.2205 14.1843L33.0205 1.68426L31.7797 0.115765L15.9796 12.6158L17.2205 14.1843Z" fill="currentColor" mask="url(#path-4-inside-1)"></path></svg></div><span class="mr-4 text-base leading-4" data-testid="email-alerts-link">Email alerts</span></div></a></div></div><div class="prose mx-auto mb-[24px] w-full max-w-screen-2xl px-4 pb-10 lg:pb-20 xl:w-[85%]"><div class="flex items-center justify-center bg-white pb-6 md:flex-row md:justify-between lg:justify-between xl:justify-between"><div class="text-bmj-silver-800 custom-top-box mr-2 w-fit text-center text-xs lg:text-lg" data-testid="publishingDate"><div class="flex flex-wrap items-center justify-center gap-[8px]"><span class="w-full text-center text-[14px] font-bold leading-[20px] md:w-auto md:text-[16px] md:leading-[24px] lg:w-auto xl:w-auto">Original Research</span><span class="text-bmj-bg-separator hidden w-[4px] text-[8px] leading-[20px] md:block lg:block xl:block">•</span><button type="button" aria-haspopup="dialog" aria-expanded="false" aria-controls="radix-:R3arpuuuuuj4ja:" data-state="closed" id="publication-icon" data-testid="publication-icon" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 [&_span]:focus-visible:text-bmj-silver-800 focus-visible:border-bmj-silver-500 not-prose rounded-md text-[12px] focus-visible:border-[1px] focus-visible:outline-none sm:text-[14px]"><span class="share-link text-bmj-blue-600 hover:text-bmj-blue-700 text-[14px] leading-[20px] md:text-[16px] md:leading-[24px]">20 December 2022</span><img src="/next-resources/publication-details.svg" alt="publication details" class="ml-[2px] mt-[-4px] inline max-h-[16px]" /></button><span class="text-bmj-bg-separator w-[4px] text-[8px] leading-[20px]">•</span><button type="button" aria-haspopup="dialog" aria-expanded="false" aria-controls="radix-:Rkarpuuuuuj4ja:" data-state="closed" id="open-access-icon" data-testid="open-access-icon" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 [&_span]:focus-visible:text-bmj-silver-800 focus-visible:border-bmj-silver-500 not-prose rounded-md text-[12px] focus-visible:border-[1px] focus-visible:outline-none sm:text-[14px]"><span class="share-link text-[14px] leading-[20px] font-bold"></span><span class="flex gap-[1px]"><img src="/next-resources/open-access.svg" alt="open access icon" class="mt-0 inline h-[20px] text-[16px] leading-[24px]" data-testid="open-access-icon-img" /></span></button></div></div><div class="mt-[6px] flex justify-between sm:mt-0 lg:flex-row" id="buttons"><div class="ml-[17.88px] flex items-center"><div data-testid="rights-and-permissions" class="text-sm leading-[1.375rem]"><a id="request-permissions" data-testid="request-permissions" target="_blank" rel="noreferrer" class="focus-visible:border-bmj-silver-500 [&_span]:focus-visible:text-bmj-silver-800 hover:text-bmj-blue-700 inline-flex items-center rounded-md text-sm no-underline focus:outline-none focus-visible:border-[1px]" href="https://s100.copyright.com/AppDispatchServlet?publisherName=BMJ&publication=svnbmj&oa=CC-BY-NC-4.0&title=Deeper%20cerebral%20hypoperfusion%20leads%20to%20spatial%20cognitive%20impairment%20in%20mice&publicationDate=2022-12-20&author=&contentID=10.1136/svn-2022-001594&volumeNum=7&issueNum=6&startPage=527&endPage=533&numPages=&copyright=Copyright%20%C2%A9%20:YEAR:,%20The%20Author(s).%20Published%20by%20BMJ%20Publishing%20Group%20Ltd.%20on%20behalf%20of%20Chinese%20Stroke%20Association.&orderBeanReset=true"><span data-testid="request-permissions-text" class="request-permissions-text text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 text-[14px] font-bold leading-[20px]">Request permission</span><img data-testid="request-permissions-img" src="/next-resources/vector.svg" alt="request permission icon" class="my-0 ml-[5.88px] h-[16.25px] w-[16.25px]" /></a></div></div><div class="ml-[17.88px] flex items-center" data-testid="citation"></div><div class="ml-[17.88px] flex items-center" data-testid="share"></div><div class="ml-[17.88px] hidden h-12 sm:w-[150px] md:block" data-testid="pdf"><div><a href="/content/svnbmj/7/6/527.full.pdf" target="_blank" rel="noreferrer" class="flex flex-row items-center no-underline" data-testid="pdf-button-link"><button class="bg-bmj-blue-600 hover:bg-bmj-blue-700 active:bg-bmj-blue-800 focus-visible:outline-bmj-silver-500 h-[44px] w-full rounded-lg"><span class="flex h-full items-center justify-center text-sm font-bold leading-6 text-white">Download PDF <img src="/next-resources/download-pdf.svg" alt="" class="ml-[11.54px]" data-testid="Download-pdf-arrow" /></span></button></a></div></div></div></div><div class="col-span-12 mt-2 bg-white md:mt-0"><div><h1 id="article-title-1" class="text-bmj-silver-800 mb-6 text-center text-[1.75rem] font-normal leading-[2.25rem] md:text-left lg:text-[2.625rem] lg:leading-[3.063rem]" data-testid="title">Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice</h1></div></div><div class="bg-white"><div class="relative"><div class="max-h-[95px] md:h-[30px] invisible absolute overflow-hidden text-center md:text-left"><span class="block md:inline" id="author-affiliations-button"><button type="button" aria-haspopup="dialog" aria-expanded="false" aria-controls="radix-:Rlcrpuuuuuj4ja:" data-state="closed" id="" data-testid="" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 [&_span]:focus-visible:text-bmj-silver-800 focus-visible:border-bmj-silver-500 not-prose rounded-md text-[12px] focus-visible:border-[1px] focus-visible:outline-none sm:text-[14px]"><p id="author-affiliations" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 not-prose mb-2 mr-1 inline-block text-[14px] leading-5 underline decoration-1 underline-offset-4 hover:decoration-2">Author affiliations</p></button><span class="text-bmj-blue-600 mb-2 mr-1 text-[14px] leading-5">•</span></span><span class="mr-2"><button type="button" aria-haspopup="dialog" aria-expanded="false" aria-controls="radix-:R4pcrpuuuuuj4ja:" data-state="closed" id="" data-testid="" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 [&_span]:focus-visible:text-bmj-silver-800 focus-visible:border-bmj-silver-500 not-prose rounded-md text-[12px] focus-visible:border-[1px] focus-visible:outline-none sm:text-[14px]"><p id="author-list" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 not-prose group mb-2 text-center text-[14px] leading-5"><span class="inline"><span data-testid="author-list-name-0" class="border-bmj-blue-600 relative inline underline decoration-1 underline-offset-4 group-hover:decoration-2">Zhiyuan Zhou</span><sup class="ml-1 inline">1</sup></span></p></button>,</span><span class="mr-2"><button type="button" aria-haspopup="dialog" aria-expanded="false" aria-controls="radix-:R59crpuuuuuj4ja:" data-state="closed" id="" data-testid="" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 [&_span]:focus-visible:text-bmj-silver-800 focus-visible:border-bmj-silver-500 not-prose rounded-md text-[12px] focus-visible:border-[1px] focus-visible:outline-none sm:text-[14px]"><p id="author-list" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 not-prose group mb-2 text-center text-[14px] leading-5"><span class="inline"><span data-testid="author-list-name-1" class="border-bmj-blue-600 relative inline underline decoration-1 underline-offset-4 group-hover:decoration-2">Yuanyuan Ma</span><sup class="ml-1 inline">1</sup></span></p></button>,</span><span class="mr-2"><button type="button" aria-haspopup="dialog" aria-expanded="false" aria-controls="radix-:R5pcrpuuuuuj4ja:" data-state="closed" id="" data-testid="" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 [&_span]:focus-visible:text-bmj-silver-800 focus-visible:border-bmj-silver-500 not-prose rounded-md text-[12px] focus-visible:border-[1px] focus-visible:outline-none sm:text-[14px]"><p id="author-list" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 not-prose group mb-2 text-center text-[14px] leading-5"><span class="inline"><span data-testid="author-list-name-2" class="border-bmj-blue-600 relative inline underline decoration-1 underline-offset-4 group-hover:decoration-2">Tongtong Xu</span><sup class="ml-1 inline">2</sup></span></p></button>,</span><span class="mr-2"><button type="button" aria-haspopup="dialog" aria-expanded="false" aria-controls="radix-:R69crpuuuuuj4ja:" data-state="closed" id="" data-testid="" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 [&_span]:focus-visible:text-bmj-silver-800 focus-visible:border-bmj-silver-500 not-prose rounded-md text-[12px] focus-visible:border-[1px] focus-visible:outline-none sm:text-[14px]"><p id="author-list" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 not-prose group mb-2 text-center text-[14px] leading-5"><span class="inline"><span data-testid="author-list-name-3" class="border-bmj-blue-600 relative inline underline decoration-1 underline-offset-4 group-hover:decoration-2">Shengju Wu</span><sup class="ml-1 inline">2</sup></span></p></button>,</span><span class="mr-2"><button type="button" aria-haspopup="dialog" aria-expanded="false" aria-controls="radix-:R6pcrpuuuuuj4ja:" data-state="closed" id="" data-testid="" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 [&_span]:focus-visible:text-bmj-silver-800 focus-visible:border-bmj-silver-500 not-prose rounded-md text-[12px] focus-visible:border-[1px] focus-visible:outline-none sm:text-[14px]"><p id="author-list" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 not-prose group mb-2 text-center text-[14px] leading-5"><span class="inline"><span data-testid="author-list-name-4" class="border-bmj-blue-600 relative inline underline decoration-1 underline-offset-4 group-hover:decoration-2">Guo-Yuan Yang</span><sup class="ml-1 inline">2</sup></span></p></button>,</span><span class="mr-2"><button type="button" aria-haspopup="dialog" aria-expanded="false" aria-controls="radix-:R79crpuuuuuj4ja:" data-state="closed" id="" data-testid="" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 [&_span]:focus-visible:text-bmj-silver-800 focus-visible:border-bmj-silver-500 not-prose rounded-md text-[12px] focus-visible:border-[1px] focus-visible:outline-none sm:text-[14px]"><p id="author-list" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 not-prose group mb-2 text-center text-[14px] leading-5"><span class="inline"><span data-testid="author-list-name-5" class="border-bmj-blue-600 relative inline underline decoration-1 underline-offset-4 group-hover:decoration-2">Jing Ding</span><sup class="ml-1 inline">1</sup></span><span class="ml-1 inline-block"><img data-testid="author-list-orcid-icon-5" class="m-0 inline max-h-4" src="https://orcid.org/sites/default/files/images/orcid_16x16.png" alt="orcid logo" width="16" height="16" /></span><span id="author-list-envelope-icon" class="ml-1 inline"><img src="/next-resources/mail.svg" alt="email" data-testid="envelope-image-5" class="m-0 inline max-h-4" width="16" height="16" /></span></p></button>,</span><span class="mr-2"><button type="button" aria-haspopup="dialog" aria-expanded="false" aria-controls="radix-:R7pcrpuuuuuj4ja:" data-state="closed" id="" data-testid="" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 [&_span]:focus-visible:text-bmj-silver-800 focus-visible:border-bmj-silver-500 not-prose rounded-md text-[12px] focus-visible:border-[1px] focus-visible:outline-none sm:text-[14px]"><p id="author-list" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 not-prose group mb-2 text-center text-[14px] leading-5"><span class="inline"><span data-testid="author-list-name-6" class="border-bmj-blue-600 relative inline underline decoration-1 underline-offset-4 group-hover:decoration-2">Xin Wang</span><sup class="ml-1 inline">1 3</sup></span><span id="author-list-envelope-icon" class="ml-1 inline"><img src="/next-resources/mail.svg" alt="email" data-testid="envelope-image-6" class="m-0 inline max-h-4" width="16" height="16" /></span></p></button>.</span><div class="inline-block" id="show-all-button"><span class="mr-1">...</span><button class="inline-flex gap-1"><span class="bg-bmj-blue-10 text-bmj-blue-600 flex items-center gap-1 rounded-[8px] px-2 py-1 text-[14px] font-bold leading-5"><span class="bg-bmj-blue-600 flex h-4 min-w-[16px] items-center justify-center rounded-[92px] p-1 text-[12px] font-normal leading-4 text-white">0</span><span>Show all authors</span><svg class="mx-1 h-[7px] w-[13px]" viewBox="0 0 16 8" fill="none" xmlns="http://www.w3.org/2000/svg"><path fill-rule="evenodd" clip-rule="evenodd" d="M0.26035 0.234315C0.607482 -0.0781049 1.1703 -0.0781049 1.51743 0.234315L8 6.06863L14.4826 0.234315C14.8297 -0.0781049 15.3925 -0.0781049 15.7396 0.234315C16.0868 0.546734 16.0868 1.05327 15.7396 1.36569L8.62854 7.76569C8.28141 8.0781 7.71859 8.0781 7.37146 7.76569L0.26035 1.36569C-0.0867832 1.05327 -0.0867832 0.546734 0.26035 0.234315Z" fill="currentColor"></path></svg></span></button></div></div><div class="w-full animate-pulse"><span class="flex mb-[8px] mt-[5px] justify-center gap-2"><div class="bg-bmj-silver-50 h-[20px] w-[75%] rounded md:w-[10%] hidden md:inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[55%] rounded md:w-[15%] hidden md:inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[30%] rounded md:w-[30%] hidden md:inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[70%] rounded md:w-[20%] hidden md:inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[45%] rounded md:w-[5%] hidden md:inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[25%] rounded md:w-[20%]"></div></span><span class="flex md:hidden mb-[8px] mt-[5px] justify-center gap-2"><div class="bg-bmj-silver-50 h-[20px] w-[75%] rounded md:w-[10%] inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[55%] rounded md:w-[15%] inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[30%] rounded md:w-[30%] inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[70%] rounded md:w-[20%] inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[45%] rounded md:w-[5%] inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[25%] rounded md:w-[20%]"></div></span><span class="flex md:hidden mb-[8px] mt-[5px] justify-center gap-2"><div class="bg-bmj-silver-50 h-[20px] w-[75%] rounded md:w-[10%] inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[55%] rounded md:w-[15%] inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[30%] rounded md:w-[30%] inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[70%] rounded md:w-[20%] inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[45%] rounded md:w-[5%] inline-block"></div><div class="bg-bmj-silver-50 h-[20px] w-[25%] rounded md:w-[20%]"></div></span></div></div><div class="mt-6 grid h-12 w-full md:mt-0 md:hidden" data-testid="pdf"><button type="button" aria-haspopup="dialog" aria-expanded="false" aria-controls="radix-:Rkrpuuuuuj4ja:" data-state="closed" id="three-dot-icon" data-testid="three-dot-icon" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 [&_span]:focus-visible:text-bmj-silver-800 focus-visible:border-bmj-silver-500 not-prose w-full rounded-md text-[12px] focus-visible:border-[1px] focus-visible:outline-none sm:text-[14px]"><span data-testid="share-text" class="bg-bmj-blue-600 hover:bg-bmj-blue-700 active:bg-bmj-blue-800 focus-visible:outline-bmj-silver-500 block h-[44px] w-full rounded-lg md:hidden"><span class="flex h-full items-center justify-center text-sm font-bold leading-6 text-white">Article options</span></span><span class="share-cite-rights-tooltip bg-share-icon-bg hidden h-[44px] w-[44px] rounded-[8px] pb-[12px] pl-[16px] pr-[16px] pt-[12px] md:block lg:block"><img src="/next-resources/tooltip.svg" alt="Tooltip icon" class="m-auto h-full" /></span></button></div></div><div class="grid grid-cols-[3fr_1fr] gap-x-4 gap-y-4 md:grid-cols-[auto_332px]"><div class="col-span-2 mb-2 pt-[40px] md:mb-6 lg:col-span-1"><div><div xmlns="http://www.w3.org/1999/xhtml" class="article fulltext-view flex flex-col -mb-6"><div class="abstract-section" id="abstract-1"><h2>Abstract</h2><div id="sec-1" class="subsection"><p id="p-2"><strong>Background</strong> Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.</p></div><div id="sec-2" class="subsection"><p id="p-3"><strong>Methods</strong> Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.</p></div><div id="sec-3" class="subsection"><p id="p-4"><strong>Results</strong> These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p<0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p<0.05) and caused acute instead of prolonged impairment of spatial reference memory (p<0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p<0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p>0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p<0.05).</p></div><div id="sec-4" class="subsection"><p id="p-5"><strong>Conclusion</strong> We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI.</p></div><button data-testid="back-to-top-button" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 focus-visible:border-bmj-silver-500 mt-[16px] rounded-md focus-visible:border-[1px] focus-visible:outline-none">Back to top</button></div><div class="section notes text-bmj-silver-800 border-bmj-silver-100 [&_h3]:text-bmj-silver-800 mb-[40px] border-[1px] px-[24px] pt-[8px] pb-[16px] [&_p]:my-[8px] [&_ul]:m-0 [&_ul]:list-none [&_ul]:p-0 [&_li]:m-0 [&_li]:p-0 [&_h3]:mb-0 [&_h3]:mt-[16px] [&_h3]:text-[1.25rem] [&_h3]:font-normal"><div data-testid="article-notes-content" class="article-notes-content"><div class="" id="boxed-text-1"><div id="sec-5" class="subsection"><h3>What is already known on this topic</h3><ul class="list-unord " id="list-1"><li id="list-item-1"><p id="p-6">Cerebral ischaemia or hypoperfusion leads to cognitive impairment in experimental mouse models.</p></li></ul></div><div id="sec-6" class="subsection"><h3>What this study adds</h3><ul class="list-unord " id="list-2"><li id="list-item-2"><p id="p-7">This study elucidates different cerebral ischaemia and spatial cognitive impairment patterns in three common vascular cognitive impairment (VCI) mouse models.</p></li></ul></div><div id="sec-7" class="subsection"><h3>How this study might affect research, practice and/or policy</h3><ul class="list-unord " id="list-3"><li id="list-item-3"><p id="p-8">Researchers can use 0.16/0.18 mm bilateral common carotid artery stenosis as an alternative VCI mouse model when they study the mechanism and the development of VCI therapy.</p></li></ul></div></div></div></div><div class="article-body-sections wrap-urls md:[&_h2]:text-[2.125rem]" data-testid="article-body-section"><section id="sec-8"><h2 class="">Introduction</h2><p id="p-9">Vascular cognitive impairment (VCI) represents the second-leading cause of dementia after Alzheimer’s disease, accounting for 15%–40% of all dementia cases.<a id="xref-ref-1-1" class="xref-bibr" href="#ref-1">1 2</a> The development of VCI is a complex consequence of various cardiovascular and cerebrovascular events, such as cerebral small vessel disease, multi-infarct dementia, strategic infarct, severe hypoperfusion, hereditary vasculopathy and other haemorrhagic cerebrovascular diseases.<a id="xref-ref-3-1" class="xref-bibr" href="#ref-3">3 4</a> In VCI patients, the main cerebrovascular pathologies are usually cortical and subcortical micro, multiple infarcts and white matter hyperintensities due to chronic or/and acute compromised cerebral blood flow (CBF) in the whole brain or specific brain regions. The other neuropathophysiological changes include: brain–blood barrier breakdown, myelin loss, arteriolosclerosis, leptomeningeal cerebral amyloid angiopathy and perivascular space dilation, etc.<a id="xref-ref-5-1" class="xref-bibr" href="#ref-5">5 6</a> Although much has known about VCI, the precise mechanism that how these neurovascular pathologies translate to cognitive function decline remains unrevealed.</p><p id="p-10">Currently, more than 16 rodents experimental models have been developed to mimic neuropathological features and symptoms of human VCI.<a id="xref-ref-7-1" class="xref-bibr" href="#ref-7">7</a> Usually, most experimental VCI models depended on generating chronic cerebral hypoperfusion (CCH) condition, resulting in white matter injury, neuronal loss, axonal damage and cognitive impairment in animals.<a id="xref-ref-7-2" class="xref-bibr" href="#ref-7">7 8</a> Apart from CCH, some studies found transient cerebral hypoperfusion could also cause acute or remote neurological damage and subsequently resulted in cognitive impairment.<a id="xref-ref-9-1" class="xref-bibr" href="#ref-9">9</a> Although CCH is a key mechanism leading to VCI and dementia, none of CCH models could replicate all neuropathological abnormalities in VCI patients because simply blocking or narrowing major cervical artery could not completely cause real cerebral ischaemia pattern occurring in VCI patients.<a id="xref-ref-10-1" class="xref-bibr" href="#ref-10">10</a> Therefore, it is necessary to know the different characteristic of these experimental animal models for selecting an better model for experimental studies and clinical translation of drugs and therapies.</p><p id="p-11">Among all animals, rodent species, especially C57/BL6 mouse strain were preferred to be used to establish VCI model because of many advantages: such as less drug dosage, easier handling, and more importantly, higher vulnerability to cerebral ischaemia because of incomplete circle of Willis.<a id="xref-ref-11-1" class="xref-bibr" href="#ref-11">11</a> Therefore, this study established three commonly used experimental mouse models of VCI using C57/BL6 mouse strain by ligation or stenosis of common carotid arteries (CCAs), namely transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion (rUCCAO). For BCAS models, we set three subgroups according to different extents of CCA stenosis caused by microcoils with different inner diameters (ID, eg, bilateral 0.16 mm, 0.16/0.18 mm and bilateral 0.18 mm). We aimed to clarify which mouse model is more appropriate to induce chronic brain ischaemia and closely mimicking the CBF changes of VCI patients, providing a valuable scientific research tool to elucidate the pathophysiology and develop therapeutic strategy for VCI in human.</p></section><button data-testid="back-to-top-button" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 focus-visible:border-bmj-silver-500 mt-[16px] rounded-md focus-visible:border-[1px] focus-visible:outline-none">Back to top</button></div><div class="article-body-sections wrap-urls md:[&_h2]:text-[2.125rem]" data-testid="article-body-section"><section id="sec-9"><h2 class="">Materials and methods</h2><div id="sec-10" class="subsection"><h3>Animal experimental design</h3><p id="p-12">Animal studies were reported following ARRIVE guidelines. Adult male C57/BL6 mice (8 weeks, weight 22–24 g) were provided by Beijing Vital River Laboratory Animal Technology. Mice were acclimatised for 1 week before operation. Mice were housed at 22 °C with 60% humidity and were provided ad libitum access to food and water. For CBF analysis, each experimental model’s CBF was compared with the preoperation baseline, so no control group was included. For cognitive function analysis, each model was compared with sham-operation. The experimental unit was single mouse. A total number of 118 mice were used for this study, 20 mice failed to survive from the operation because of severe cerebral ischaemia. The remaining 98 mice were further used for the whole experiment.</p></div><div id="sec-11" class="subsection"><h3>Bilateral common carotid artery stenosis</h3><p id="p-13">The BCAS model was established by using microcoils specifically designed for the mouse (microcoil specifications: piano wire diameter: 0.08 mm, total length: 2.5 mm, internal diameters: 0.16 mm and 0.18 mm, Anruike Biotechnology, Xi 'an, China). Animals (n=56) were induced anaesthesia with 5% isoflurane/95% air mixture and maintained to anaesthesia by 5% isoflurane/95% air mixture during operation. The left and right CCA were exposed and isolated from the surrounding sheaths. Then microcoils were twined by rotating it around each CCA. The site of operation was sutured. During the operation, 16 mice failed to survive because of the acute severe CBF reduction. The survived mice were observed and taken care of post-operation until being conscious and recovered to freely access food and water ad libitum. The operated mice were further divided into three subgroups according to different internal diameters of the microcoils: 0.16 mm group (n=7), 0.16/0.18 mm (0.16 mm for the right CCA/0.18 mm for the left CCA) group (n=10) and 0.18 mm group (n=11). Mice in the control group underwent the identical operation without occlusion of CCAs (n=12).</p></div><div id="sec-12" class="subsection"><h3>tBCCAO and rUCCAO</h3><div id="sec-13" class="subsection"><h4>Transient bilateral common carotid artery occlusion</h4><p id="p-14">Anesthetisation procedure was same as the BCAS model. The right and left CCAs were isolated from the adjacent nerves and surrounding sheaths, and both CCAs were occluded with microvascular clips (RWD life sciences, Shenzhen, China) for 20 min. Then the clips were removed to allow CBF reperfusion and incisions were sutured. Mice in the control group were sham-operated for 20 min without occlusion of CCAs. After the operation, mice were kept in their quarters with food and water available ad libitum.</p></div><div id="sec-14" class="subsection"><h4>Right unilateral common carotid artery occlusion</h4><p id="p-15">Mice were administered and fixed on the operation table on supine position. The right CCA was isolated from the adjacent nerves and ligated with a 6–0 silk suture to achieve rUCCAO. A total number of 62 mice were used for the operation, in which 4 mice died during the operation because of severe cerebral ischaemia, the survived mice were used for the following experiments (tBCCAO group, n=33; rUCCAO group, n=12; control group, n=13).</p></div></div><div id="sec-15" class="subsection"><h3>Surface CBF measurement</h3><p id="p-16">The surface CBF of each time point of animal models were measured by laser Doppler flowmetry (Moor Instruments, Devon, UK). The measurement method of the surface CBF was described as our previous study.<a id="xref-ref-12-1" class="xref-bibr" href="#ref-12">12</a> Briefly, mice were anaesthetised with isoflurane and their scalp was cut to expose the skull. The detector was then placed on the skull 1 mm posterior and 2 mm lateral to the bregma and held for a few seconds until the floating CBF value was stabilised. Then, the CBF value was recorded, and the scalp was sutured.</p></div><div id="sec-16" class="subsection"><h3>Laser speckle contrast imaging</h3><p id="p-17">Laser speckle contrast imaging (LSCI) measurement method was described as our previous study.<a id="xref-ref-13-1" class="xref-bibr" href="#ref-13">13</a> Briefly, mice were anaesthetised and heads were fixed in a stereotaxic frame. Then mice were placed under the LSCI equipment (RFLSI Pro, RWD life sciences, Shenzhen, China). The scalp of mice were cut by surgical scissors and the surface of the skulls were exposed and illuminated with a 784 nm/32 mW laser with a beam expander and light intensity was controlled by a polariser. The CBF images were detected by a CCD camera and the image acquisitions were performed using custom software (RWD life science). Three hundred frames were acquired at 10 Hz with 10 ms exposure time.</p></div><div id="sec-17" class="subsection"><h3>Morris water maze test</h3><p id="p-18">The Morris water maze (MWM) protocol in this study was followed by Vorhees <em>et al</em>.<a id="xref-ref-14-1" class="xref-bibr" href="#ref-14">14</a> Mice were subjected to MWM test for spatial learning and memory evaluation. A circular pool (diameter: 20 cm; height: 50 cm) filled with water at 22 °C was divided into four equal quadrants. A video camera was hanging over the pool and four different references were hung on the wall of different directions. A white platform (diameter: 8 cm) was submerged 1 cm below the surface of the water surface. The position of each reference inside and outside the maze was kept unchanged during the training sessions. For the acquisition period, each mouse received one session per day for 5 days (D1–D5) consecutively. Each session consisted of four trials with an interval of 10 min. During each trial, mice were gently placed in the pool towards the wall of the maze at one of the four starting positions. The time mice spending on finding the hidden platform (escape latency) and the swimming track were automatically recorded by the Anymaze software (Stoelting, Naperville, USA). The maximum test time for each per is 60 s. If the mouse failed to locate the target platform within 60 s, then it was guided to the platform and stayed for 15 s. On D6, the platform was removed, mice were subjected to a probe test. The time and distance mice spending in the target quadrant (quadrant concluding the platform) and times that mice crossed the platform area were all recorded by the Anymaze software.</p></div><div id="sec-18" class="subsection"><h3>Statistical analysis</h3><p id="p-19">All statistical analyses were performed using the GraphPad Prism V.8.0 (GraphPad Software, San Diego, USA). The normality of all data was analysed by D'Agostino and Pearson omnibus normality test. The significance of differences was determined by one-way analysis of variance, followed by multiple comparisons between the control group and experimental model groups. All values were presented as mean±SEM <em>P</em>＜0.05 was consider significant difference. *Indicated p＜0.05; **indicated p＜0.01; ***indicated p＜0.001.</p><div id="sec-19" class="subsection"><h4>Randomisation</h4><p id="p-20">No randomisation method was used in this study, animals were open-labelled according to the number registered in Anymaze software.</p></div><div id="sec-20" class="subsection"><h4>Inclusion and exclusion criteria of animals</h4><p id="p-21">The assays of CBF changes and cognitive impairment were exploratory in this study, so no inclusion and exclusion criteria were used.</p></div></div></section><button data-testid="back-to-top-button" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 focus-visible:border-bmj-silver-500 mt-[16px] rounded-md focus-visible:border-[1px] focus-visible:outline-none">Back to top</button></div><div class="article-body-sections wrap-urls md:[&_h2]:text-[2.125rem]" data-testid="article-body-section"><section id="sec-21"><h2 class="">Results</h2><div id="sec-22" class="subsection"><h3>CBF changes in three cerebral hypoperfusion models</h3><p id="p-22">We first examined haemodynamic changes in BCAS mice. BCAS subgroups operation procedure was shown in <a id="xref-fig-1-1" class="xref-fig" href="#F1">figure 1A</a>. The representation of CBF change detected by LSCI for each BCAS subgroup was shown in <a id="xref-fig-1-2" class="xref-fig" href="#F1">figure 1B</a>. We found that the CBF in 0.16 mm group reduced to bilaterally 45%–50% of baseline postoperation, recovered to about 60% after 1 week and reached 70% of the baseline after 4 weeks (<a id="xref-fig-1-3" class="xref-fig" href="#F1">figure 1C</a>). In mice of 0.16/0.18 mm group, the CBF of the right hemisphere (subject to ID=0.16 mm microcoil) declined to 45%–50% of baseline level postoperation and gradually recovered to 65%–70% after 4 weeks. The CBF of left hemisphere (subject to ID=0.18 mm microcoil) decreased to 55%–60% postoperation and gradually recovered to 70% 4 weeks later (<a id="xref-fig-1-4" class="xref-fig" href="#F1">figure 1D</a>). In mice of 0.18 mm group, CBF decreased bilaterally to 60%–65% of baseline postoperation, and then gradually recovered to about 80% of baseline by the fourth week (<a id="xref-fig-1-5" class="xref-fig" href="#F1">figure 1E</a>). The rUCCAO and tBCCAO operation procedures were shown in <a id="xref-fig-2-1" class="xref-fig" href="#F2">figure 2A</a>. The representations of CBF change detected by LSCI for rUCCAO and tBCCAO mice were shown in <a id="xref-fig-2-2" class="xref-fig" href="#F2">figure 2B</a>. In mice of rUCCAO group, the CBF was reduced to around 55% of baseline while the contralateral CBF reduced about 10%–15% compared with preoperation. One-week postoperation, ipsilateral CBF returned to 75%–80% and the contralateral CBF recovered to baseline level. Four weeks later, the ipsilateral CBF recovered to 80% of baseline level and contralateral CBF stayed nearly 100% (<a id="xref-fig-2-3" class="xref-fig" href="#F2">figure 2C</a>). In mice of tBCCAO group, the bilateral CBF decreased to approximately 10% of baseline level and returned to 100% after releasing vascular clamps. The bilateral CBF showed no significant difference from the first to the fourth week (<a id="xref-fig-2-4" class="xref-fig" href="#F2">figure 2D</a>).</p><div id="F1" class="flex items-center justify-center"><section class="my-4"><img id="F1" class="mb-2 mt-[20px] max-h-full max-w-full cursor-pointer object-contain" src="/content/svnbmj/7/6/527/F1.medium.gif" alt="Figure 1" height="400" /></section></div><div class="mb-4"><a id="request-permissions" data-testid="request-permissions" target="_blank" rel="noreferrer" class="focus-visible:border-bmj-silver-500 [&_span]:focus-visible:text-bmj-silver-800 hover:text-bmj-blue-700 inline-flex items-center rounded-md text-sm no-underline focus:outline-none focus-visible:border-[1px]" href="https://s100.copyright.com/AppDispatchServlet?publisherName=BMJ&publication=svnbmj&oa=CC-BY-NC-4.0&title=Deeper%20cerebral%20hypoperfusion%20leads%20to%20spatial%20cognitive%20impairment%20in%20mice&publicationDate=2022-12-20&author=&contentID=10.1136/svn-2022-001594&volumeNum=7&issueNum=6&startPage=527&endPage=533&numPages=&copyright=Copyright%20%C2%A9%20:YEAR:,%20The%20Author(s).%20Published%20by%20BMJ%20Publishing%20Group%20Ltd.%20on%20behalf%20of%20Chinese%20Stroke%20Association.&orderBeanReset=true"><span data-testid="request-permissions-text" class="request-permissions-text text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 text-[14px] font-bold leading-[20px]">Request permission</span><img data-testid="request-permissions-img" src="/next-resources/vector.svg" alt="request permission icon" class="my-0 ml-[5.88px] h-[16.25px] w-[16.25px]" /></a></div><section class="fig-caption"><span>Figure 1</span><p>CBF changes and mortalities of BCAS models (A) Schematic representation of BCAS operation (grouping by different inner diameters of the microcoils). (B) Representation of laser speckle contrast image on BCAS model subgroups at preoperation, 2 hours postoperation, and 1 week, 2 weeks, 4 weeks postoperation. (C–E) Numerical representation of CBF changes measured by laser Doppler flowmetry at preoperation, 2 hours postoperation, and 1 week, 2 weeks, 3 weeks and 4 weeks postoperation. (C) The 0.16 mm subgroup of the BCAS model. (D) The 0.16/0.18 mm subgroup of the BCAS model. (E) The 0.18 mm subgroup of the BCAS model. n=5/group. (F) The mortality of different subgroups. All data were represented as mean±SEM. ***P<0.001. BCAS, bilateral common carotid artery stenosis; CBF, cerebral blood flow.</p></section><div id="F2" class="flex items-center justify-center"><section class="my-4"><img id="F2" class="mb-2 mt-[20px] max-h-full max-w-full cursor-pointer object-contain" src="/content/svnbmj/7/6/527/F2.medium.gif" alt="Figure 2" height="400" /></section></div><div class="mb-4"><a id="request-permissions" data-testid="request-permissions" target="_blank" rel="noreferrer" class="focus-visible:border-bmj-silver-500 [&_span]:focus-visible:text-bmj-silver-800 hover:text-bmj-blue-700 inline-flex items-center rounded-md text-sm no-underline focus:outline-none focus-visible:border-[1px]" href="https://s100.copyright.com/AppDispatchServlet?publisherName=BMJ&publication=svnbmj&oa=CC-BY-NC-4.0&title=Deeper%20cerebral%20hypoperfusion%20leads%20to%20spatial%20cognitive%20impairment%20in%20mice&publicationDate=2022-12-20&author=&contentID=10.1136/svn-2022-001594&volumeNum=7&issueNum=6&startPage=527&endPage=533&numPages=&copyright=Copyright%20%C2%A9%20:YEAR:,%20The%20Author(s).%20Published%20by%20BMJ%20Publishing%20Group%20Ltd.%20on%20behalf%20of%20Chinese%20Stroke%20Association.&orderBeanReset=true"><span data-testid="request-permissions-text" class="request-permissions-text text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 text-[14px] font-bold leading-[20px]">Request permission</span><img data-testid="request-permissions-img" src="/next-resources/vector.svg" alt="request permission icon" class="my-0 ml-[5.88px] h-[16.25px] w-[16.25px]" /></a></div><section class="fig-caption"><span>Figure 2</span><p>Cerebral blood flow (CBF) changes and mortalities of right unilateral common carotid artery occlusion (rUCCAO) and transient bilateral common carotid arteries occlusion (tBCCAO) models (A) Schematic representation of tBCCAO and rUCCAO operation. (B) Representation of laser speckle contrast image of rUCCAO and tBCCAO models at preoperation, 2 hours postoperation (rUCCAO)/immediately postoperation (tBCCAO), and 1 week, 2 weeks, 4 weeks postoperation. (C–D) Numerical representation of CBF changes measured by laser Doppler flowmetry (LDF) at preoperation, 2 hours postoperation (rUCCAO)/immediately postoperation (tBCCAO), and 1 week, 2 weeks, 3 weeks and 4 weeks postoperation. n=5/group. (C) rUCCAO. (D) tBCCAO. (E) Mortalities of tBCCAO and rUCCAO operation. All data were represented as mean±SEM. ns indicated not significant.</p></section></div><div id="sec-23" class="subsection"><h3>Mortality</h3><p id="p-25">The mortality of 0.16 mm, 0.16/0.18 mm and 0.18 mm group in the BCAS model reached nearly 75%, 20% and around 15%, respectively (<a id="xref-fig-1-6" class="xref-fig" href="#F1">figure 1E</a>). The mortality of rUCCAO and 20 min-tBCCAO models was both around 10% (<a id="xref-fig-2-5" class="xref-fig" href="#F2">figure 2E</a>).</p></div><div id="sec-24" class="subsection"><h3>Spatial reference memory and study function</h3><div id="sec-25" class="subsection"><h4>Bilateral common carotid artery stenosis</h4><p id="p-26">Four weeks’ postoperation, the spatial reference study and memory of the 0.18 mm group was not statistically different compared with the control group (<a id="xref-fig-3-1" class="xref-fig" href="#F3">figure 3A–D</a>), while both 0.16 mm and 0.16/0.18 mm group showed significantly impairment of cognitive function as evidenced by a slower study rate to locate the platform (<a id="xref-fig-3-2" class="xref-fig" href="#F3">figure 3A</a>) and less time spent in the target quadrant as well as less crosses to the platform area (<a id="xref-fig-3-3" class="xref-fig" href="#F3">figure 3B,C</a>). Notably, mice in 0.18 mm and 0.16/0.18 mm groups showed no motor ability impairment after 4 weeks, while mice in 0.16 mm group showed motor ability impairment evaluated by the swimming speed (<a id="xref-fig-3-4" class="xref-fig" href="#F3">figure 3D</a>).</p></div><div id="sec-26" class="subsection"><h4>Transient bilateral common carotid arteries occlusion</h4><p id="p-27">Mice underwent tBCCAO showed significant decline in spatial reference study function at first and second weeks’ postoperation. However, 4 weeks’ postoperation, the performance of tBCCAO mice in MWM was not significantly different from that of the control group (<a id="xref-fig-4-1" class="xref-fig" href="#F4">figure 4A–C</a>). The tBCCAO mice did not show any impairment in motor ability in this experiment, as evidenced by no reduction in the swimming speed compared with the control group (<a id="xref-fig-4-2" class="xref-fig" href="#F4">figure 4D</a>).</p><div id="F3" class="flex items-center justify-center"><section class="my-4"><img id="F3" class="mb-2 mt-[20px] max-h-full max-w-full cursor-pointer object-contain" src="/content/svnbmj/7/6/527/F3.medium.gif" alt="Figure 3" height="400" /></section></div><div class="mb-4"><a id="request-permissions" data-testid="request-permissions" target="_blank" rel="noreferrer" class="focus-visible:border-bmj-silver-500 [&_span]:focus-visible:text-bmj-silver-800 hover:text-bmj-blue-700 inline-flex items-center rounded-md text-sm no-underline focus:outline-none focus-visible:border-[1px]" href="https://s100.copyright.com/AppDispatchServlet?publisherName=BMJ&publication=svnbmj&oa=CC-BY-NC-4.0&title=Deeper%20cerebral%20hypoperfusion%20leads%20to%20spatial%20cognitive%20impairment%20in%20mice&publicationDate=2022-12-20&author=&contentID=10.1136/svn-2022-001594&volumeNum=7&issueNum=6&startPage=527&endPage=533&numPages=&copyright=Copyright%20%C2%A9%20:YEAR:,%20The%20Author(s).%20Published%20by%20BMJ%20Publishing%20Group%20Ltd.%20on%20behalf%20of%20Chinese%20Stroke%20Association.&orderBeanReset=true"><span data-testid="request-permissions-text" class="request-permissions-text text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 text-[14px] font-bold leading-[20px]">Request permission</span><img data-testid="request-permissions-img" src="/next-resources/vector.svg" alt="request permission icon" class="my-0 ml-[5.88px] h-[16.25px] w-[16.25px]" /></a></div><section class="fig-caption"><span>Figure 3</span><p>Test of spatial reference memory and motor ability deficiency of BCAS model subgroups (A) Morris water maze (MWM) acquisition period for subgroups of the BCAS model from the starting day 1 to day 5 of the test. (B) MWM probe test on day 6. (C) Times of each mouse swimming across the platform area in probe test. (D) Times of each mouse swimming across the platform area in probe test. (E) Average swimming speed of each group on day 6. All groups were compared with the control group. All data were represented as mean±SEM. ns indicated not significant; *p＜0.05; **p＜0.01; **p＜0.001. 0.16 mm subgroup (n=7); 0.16/0.18 mm subgroup (n=10); 0.18 mm subgroup (n=11); control group (n=12). BCAS, bilateral common carotid artery stenosis.</p></section><div id="F4" class="flex items-center justify-center"><section class="my-4"><img id="F4" class="mb-2 mt-[20px] max-h-full max-w-full cursor-pointer object-contain" src="/content/svnbmj/7/6/527/F4.medium.gif" alt="Figure 4" height="400" /></section></div><div class="mb-4"><a id="request-permissions" data-testid="request-permissions" target="_blank" rel="noreferrer" class="focus-visible:border-bmj-silver-500 [&_span]:focus-visible:text-bmj-silver-800 hover:text-bmj-blue-700 inline-flex items-center rounded-md text-sm no-underline focus:outline-none focus-visible:border-[1px]" href="https://s100.copyright.com/AppDispatchServlet?publisherName=BMJ&publication=svnbmj&oa=CC-BY-NC-4.0&title=Deeper%20cerebral%20hypoperfusion%20leads%20to%20spatial%20cognitive%20impairment%20in%20mice&publicationDate=2022-12-20&author=&contentID=10.1136/svn-2022-001594&volumeNum=7&issueNum=6&startPage=527&endPage=533&numPages=&copyright=Copyright%20%C2%A9%20:YEAR:,%20The%20Author(s).%20Published%20by%20BMJ%20Publishing%20Group%20Ltd.%20on%20behalf%20of%20Chinese%20Stroke%20Association.&orderBeanReset=true"><span data-testid="request-permissions-text" class="request-permissions-text text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 text-[14px] font-bold leading-[20px]">Request permission</span><img data-testid="request-permissions-img" src="/next-resources/vector.svg" alt="request permission icon" class="my-0 ml-[5.88px] h-[16.25px] w-[16.25px]" /></a></div><section class="fig-caption"><span>Figure 4</span><p>Test of spatial reference memory and motor ability deficiency of right unilateral common carotid artery occlusion (rUCCAO) and transient bilateral common carotid arteries occlusion (tBCCAO) models. (A) Morris water maze (MWM) acquisition period for tBCCAO at 1 week, 2 weeks and 4 weeks after operation from day 1 to day 5. (B) MWM probe test on day 6. The time each mouse swimming in the quadrant including the platform area. (C) The time each mouse swimming across the platform area in probe test. (D) Average swimming speed of each group on day 6. All data were represented as mean±SEM. All groups were compared with the control group. NS indicated not significant; *p＜0.05; **p＜0.01; ***p＜0.001. tBCCAO 1 week, 2 weeks, 4 weeks group (n=11/group); rUCCAO group (n=12); control group (n=13).</p></section></div><div id="sec-27" class="subsection"><h4>Right unilateral common carotid artery occlusion</h4><p id="p-30">The rUCCAO mice showed mixed results. In the acquisition period, mice showed a longer time to find the platform compared with that in the control group, while they behaved almost as good as the control group in the probe text (<a id="xref-fig-4-3" class="xref-fig" href="#F4">figure 4B,C</a>). Similarly, rUCCAO mice showed no motor ability impairment (<a id="xref-fig-4-4" class="xref-fig" href="#F4">figure 4D</a>).</p></div></div></section><button data-testid="back-to-top-button" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 focus-visible:border-bmj-silver-500 mt-[16px] rounded-md focus-visible:border-[1px] focus-visible:outline-none">Back to top</button></div><div class="article-body-sections wrap-urls md:[&_h2]:text-[2.125rem]" data-testid="article-body-section"><section id="sec-28"><h2 class="">Discussion</h2><p id="p-31">In this study, we compared three common mouse VCI models by acute or chronic restriction of CBF. Our results showed that: (1) Bilaterally ligation of CCAs caused 90% CBF decrease in C57/BL6 mice and caused acute instead of prolonged impairment of spatial reference memory; (2) Unilateral ligation of the CCA did not cause as severe ipsilateral ischaemia as seen in tBCCAO mice but caused significant spatial memory disturbance and (3) Narrowing the CCAs by half of its diameters (ID: 0.18 mm) caused approximately 20% decrease after collateral compensatory, but did not lead to spatial reference memory after 4 weeks’ postoperation detected by MWM paradigm. However, narrowing 75% of CCAs (ID: 0.16 mm) caused severe spatial cognitive and motor function impairment with a very high mortality rate in C57/BL6 mice; (4) Both mice in 0.16/0.18 mm and 0.18 mm groups caused significant spatial cognitive impairment with only mild mortality.</p><p id="p-32">Mouse species was preferred by researchers in the field of cerebral ischaemia/hypoperfusion compared with rats due to its unique advantages, such as more vulnerability to cerebral ischaemia and easier gene modification.<a id="xref-ref-9-2" class="xref-bibr" href="#ref-9">9 15</a> As mouse stain could not survive from the permanent BCCA ligation,<a id="xref-ref-11-2" class="xref-bibr" href="#ref-11">11</a> temporary ligation of CCAs was a common procedure to construct VCI in mice in many studies.<a id="xref-ref-16-1" class="xref-bibr" href="#ref-16">16</a> Studies using the tBCCAO model demonstrated that a 5–20 min ligation of bilateral whole-brain ischaemia caused obvious neuropath physiological changes, such as blood–brain barrier breakdown, white matter injury and early or late hippocampal neuronal damage,<a id="xref-ref-5-2" class="xref-bibr" href="#ref-5">5 17 18</a> as well as decreased spatial memory and learning function.<a id="xref-ref-19-1" class="xref-bibr" href="#ref-19">19</a> In our study, mice subject to bilateral transient whole-brain ischaemia showed about 90% reduction of CBF along with acute (up to 2 weeks’ postoperation) but restorable (restored after 4 weeks) spatial cognitive impairment. Some other studies also found a decline in spatial reference memory of tBCCAO and suggested that this decline was related to delayed damage of hippocampal neurons, especially in the CA1 area.<a id="xref-ref-18-1" class="xref-bibr" href="#ref-18">18 19</a> Although the advantages of the tBCCAO model, it lacked major similitude of the real disease state because rare VCI patients were caused by single anterior-circulation ischaemia. Moreover, 20 min tBCCAO did not precisely mimic the humbler diminishments in CBF seen in CCH conditions related to human VCI caused by CCH where CBF might only be reduced by 20%–30%.<a id="xref-ref-20-1" class="xref-bibr" href="#ref-20">20</a> </p><p id="p-33">The rUCCAO model was proposed by Japanese scholar Yoshizaki <em>et al</em> as an experimental mouse model of CCH.<a id="xref-ref-21-1" class="xref-bibr" href="#ref-21">21</a> The rUCCAO model has numerous advantages compared with other models, such as more consistent CBF decrease among subjects due to easy operation, lower mortality and higher consistency within the same group. This study confirmed that the ipsilateral CBF dropped to 55% of baseline after ligation and gradually recovered to 80% after 4 weeks’ postoperation, which was much similar to that of mice in the 0.18 mm group of BCAS model. In addition, the impairment of spatial reference memory function in both of these two models was insignificant. However, other studies found that rUCCAO mice showed impaired cognitive function evaluated by novel object recognition and MWM tests.<a id="xref-ref-22-1" class="xref-bibr" href="#ref-22">22 23</a> The difference between our study and others still is unknown and needs to be further investigated.</p><p id="p-34">The mouse BCAS model was first established in 2004 with a better simulation of clinical BCCA stenosis without causing significant visual function impairment.<a id="xref-ref-24-1" class="xref-bibr" href="#ref-24">24</a> Therefore, it was soon became the widely used model for the research of CCH, white matter injury and VCI.<a id="xref-ref-25-1" class="xref-bibr" href="#ref-25">25 26</a> </p><p id="p-35">It is true that Ihara had explored the CBF reduction in BCAS mice induced by different diameter microcoils (0.16, 0.18, 0.20 and 0.22 mm).<a id="xref-ref-24-2" class="xref-bibr" href="#ref-24">24</a> However, previous studies showed that the BCAS model induced by 0.18 mm diameter microcoils could not induce consistent CBF reduction,<a id="xref-ref-27-1" class="xref-bibr" href="#ref-27">27 28</a> which limited its clinical translation. Currently, 0.16 mm and 0.18 mm diameter microcoils were most widely, while few 0.17 mm diameter microcoils were used to establish the BCAS mouse models.<a id="xref-ref-24-3" class="xref-bibr" href="#ref-24">24 29–31</a> Therefore, we chose 0.16 mm and 0.18 mm diameter microcoils to induce the BCAS models in this study. Since mice underwent chronic brain ischaemia induced by 0.16 mm diameter microcoils showed a high mortality (75%),<a id="xref-ref-32-1" class="xref-bibr" href="#ref-32">32</a> we further explored CBF reduction in BCAS mice induced by 0.16/0.18 mm diameter microcoils (using a 0.16 mm diameter microcoil on one side of the CCA and a 0.18 mm diameter microcoil on the other). We aimed to clarify whether 0.16/0.18 mm diameter microcoils achieved a balance between the mortality and severity and which diameter microcoil was more appropriate to induce the BCAS model closely mimicking the CBF changes of VCI patients. In addition, we compared the CBF reduction pattern in the BCAS model with the other common VCI mouse models including tBBCAO and rUCCAO. Lastly, the spatial reference memory impairment was investigated among these three VCI mouse models. We demonstrated that the BCAS model was more likely to decipher the haemodynamics changes in VCI patients, and the 0.16/0.18 mm diameter microcoil was more appropriate to induce the BCAS model in mice because of the relative low mortality and lasting CBF reduction. Moreover, the asymmetrical ischaemia of right and left hemispheres in this model was closer to the clinical situation in which patients with carotid plaque usually showed asymmetric stenosis of the carotid artery.<a id="xref-ref-20-2" class="xref-bibr" href="#ref-20">20 33</a> Therefore, we assumed that the 0.16/0.18 mm BCAS model was an appropriate alternative for VCI study.</p><p id="p-36">In this study, animal surgery was operated by the same experienced surgeon. All raw data were presented as mean±SEM. In addition, previous study reported similar mortality of mice with BCAS surgeries induced by 0.16 mm and 0.18 mm diameter microcoils, respectively.<a id="xref-ref-24-4" class="xref-bibr" href="#ref-24">24</a> Thus, although it exists bigger differential mortality among 16 mm group (75%), 0.16/01.8 mm group (20%) and 0.18 mm group (15%), our results were truly reflecting the effect of different diameter microcoils on CBF reduction and brain damage.</p><p id="p-37">MWM is the most widely employed behavioural test for assessing spatial cognitive function deficits. MWM is also an important behavioural paradigm for drug, molecular, and gene screening in bench studies because of its relatively good objectivity and consistency without causing injury to animals.<a id="xref-ref-34-1" class="xref-bibr" href="#ref-34">34</a> However, this study only focused on deficits in spatially reference memory 4 weeks’ postoperation and lacked exploring other dimensions of cognitive function using more paradigms, such as spatial working memory or fear-based memory. Different cognitive paradigms usually reflected impairments in different brain regions. For example, spatial working memory mainly depended on integrity of white matter while spatial memory was more on decoding function of hippocampus.<a id="xref-ref-35-1" class="xref-bibr" href="#ref-35">35 36</a> Second, we only detected cognitive impairment 4 weeks’ postoperation, which might not sufficiently estimate the impact of CCH on cognitive function since the emergence of cognitive impairment was a chronic process in real VCI patients. Some studies found that 0.18 mm BCAS mice showed impairment of motor function and spatial reference memory alone with some other pathological changes not shown within short period after 6 months.<a id="xref-ref-7-3" class="xref-bibr" href="#ref-7">7 37</a> Therefore, it is critical to further evaluate the impact of compromise CBF on the neuropathy and cognitive impairment after a longer time postoperation.</p><p id="p-38">In conclusion, our study provided valuable information for scientific researchers to choose 0.16/0.18 mm BCAS as an appropriate mouse model to elucidate the pathophysiology and develop therapeutic strategy for VCI in human.</p></section><button data-testid="back-to-top-button" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 focus-visible:border-bmj-silver-500 mt-[16px] rounded-md focus-visible:border-[1px] focus-visible:outline-none">Back to top</button></div><section class="article-body-sections order-2 mb-0"><section id="fn-group-1" class="!mt-0"><div class="wrap-urls accordion-wrapper border-bmj-silver-50 border-t"><button type="button" tabindex="0" class="text-bmj-blue-800 my-[24px] flex w-full items-center justify-between text-left text-[28px] font-normal leading-10 md:text-[34px]" data-testid="accordion-toggle-button"><span data-testid="accordion-title">Footnotes</span><img class="m-0" src="/next-resources/AccordionArrowDown.svg" alt="Open accordion" /></button><div class="mt-2 pb-[24px] hidden" data-testid="accordion-content"><div data-testid="article-footnotes"><div data-testid="footnotes"><div class="[&_p]:text-bmj-silver-800 list-none[&_ul]:m-0 m-0 [&_ul]:list-none [&_ul]:p-0" data-testid="footnotes-contents"><div><html><head><script> window.dataLayer = window.dataLayer || []; function parseCookies() { let cookieHeader = document.cookie || ""; let cookies = Object.fromEntries( cookieHeader.split("; ").map((c) => c.split("=")) ); for (let key in cookies) { if (cookies[key] === "undefined") { cookies[key] = undefined; } } return cookies; } function uuidv4() { var d = new Date().getTime(); //Timestamp var d2 = (typeof performance !== "undefined" && performance.now && performance.now() * 1000) || 0; //Time in microseconds since page-load or 0 if unsupported return "xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx".replace(/[xy]/g, function (c) { var r = Math.random() * 16; //random number between 0 and 16 if (d > 0) { //Use timestamp until depleted r = (d + r) % 16 | 0; d = Math.floor(d / 16); } else { //Use microseconds since page-load if supported r = (d2 + r) % 16 | 0; d2 = Math.floor(d2 / 16); } return (c === "x" ? r : (r & 0x3) | 0x8).toString(16); }); } function handleCookie() { let cookies = parseCookies(); let bmj_uuid = cookies.bmj_uuid; if (!bmj_uuid) { bmj_uuid = uuidv4(); cookies.bmj_uuid = bmj_uuid; } return { bmj_uuid }; } let { bmj_uuid } = handleCookie(); let bmj_ppid = parseCookies().bmj_ppid; const anonMailId = "e3b0c44298fc1c149afbf4c8996fb92427ae41e4649b934ca495991b7852b855"; let nonAnonMailId = window.dataLayer.find((item) => item.user)?.user?.mail === anonMailId ? null : window.dataLayer.find((item) => item.user)?.user?.mail; let userId = dataLayer.find((item) => item.user)?.user?.["data-ics"] ?? (dataLayer.find((item) => item.user)?.user?.mail && nonAnonMailId) ?? bmj_ppid ?? bmj_uuid; document.cookie = "bmj_ppid=" + userId + "; domain=.bmj.com; path=/; max-age=31622400; SameSite=None; Secure"; document.cookie = "bmj_uuid=" + bmj_uuid + "; domain=.bmj.com; path=/; max-age=31622400; SameSite=None; Secure"; var googletag = googletag || { cmd: [] }; googletag.cmd.push(function () { googletag.pubads().setPublisherProvidedId(userId); googletag.enableServices(); }); window.dataLayer.push({ bmj_uuid: bmj_uuid, }); </script> </head><body><div class="section fn-group" id="fn-group-1"><ul><li class="fn-other" id="fn-1"><p id="p-40">ZZ and YM contributed equally.</p></li><li class="fn-other" id="fn-2"><p id="p-41"><span class="fn-label font-bold">Correction notice:</span> This article has been amended since it was first published. There was a spelling mistake in figure 4 and this now been corrected.</p></li><li class="fn-other" id="fn-3"><p id="p-42"><span class="fn-label font-bold">Contributors:</span> ZZ collected data and wrote the manuscript; YM helped revise figures and the manuscript; TX and SW helped do the animal models and also the behavior test; G-YY helped revise the manuscript; JD and XW were responsible for the overall content as the guarantors.</p></li><li class="fn-conflict" id="fn-4"><p id="p-43"><span class="fn-label font-bold">Competing interests:</span> None declared.</p></li><li class="fn-other" id="fn-5"><p id="p-44"><span class="fn-label font-bold">Provenance and peer review:</span> Not commissioned; externally peer reviewed.</p></li></ul></div></div><div data-testid="DEA-section" class="text-bmj-silver-800 p-0"><div class="wrap-urls my-6"><p data-testid="data-availability-title" class="m-0 mb-4 text-base font-bold ">Data availability statement</p><section data-testid="data-availability-text" class="m-0"><html><head><script> window.dataLayer = window.dataLayer || []; function parseCookies() { let cookieHeader = document.cookie || ""; let cookies = Object.fromEntries( cookieHeader.split("; ").map((c) => c.split("=")) ); for (let key in cookies) { if (cookies[key] === "undefined") { cookies[key] = undefined; } } return cookies; } function uuidv4() { var d = new Date().getTime(); //Timestamp var d2 = (typeof performance !== "undefined" && performance.now && performance.now() * 1000) || 0; //Time in microseconds since page-load or 0 if unsupported return "xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx".replace(/[xy]/g, function (c) { var r = Math.random() * 16; //random number between 0 and 16 if (d > 0) { //Use timestamp until depleted r = (d + r) % 16 | 0; d = Math.floor(d / 16); } else { //Use microseconds since page-load if supported r = (d2 + r) % 16 | 0; d2 = Math.floor(d2 / 16); } return (c === "x" ? r : (r & 0x3) | 0x8).toString(16); }); } function handleCookie() { let cookies = parseCookies(); let bmj_uuid = cookies.bmj_uuid; if (!bmj_uuid) { bmj_uuid = uuidv4(); cookies.bmj_uuid = bmj_uuid; } return { bmj_uuid }; } let { bmj_uuid } = handleCookie(); let bmj_ppid = parseCookies().bmj_ppid; const anonMailId = "e3b0c44298fc1c149afbf4c8996fb92427ae41e4649b934ca495991b7852b855"; let nonAnonMailId = window.dataLayer.find((item) => item.user)?.user?.mail === anonMailId ? null : window.dataLayer.find((item) => item.user)?.user?.mail; let userId = dataLayer.find((item) => item.user)?.user?.["data-ics"] ?? (dataLayer.find((item) => item.user)?.user?.mail && nonAnonMailId) ?? bmj_ppid ?? bmj_uuid; document.cookie = "bmj_ppid=" + userId + "; domain=.bmj.com; path=/; max-age=31622400; SameSite=None; Secure"; document.cookie = "bmj_uuid=" + bmj_uuid + "; domain=.bmj.com; path=/; max-age=31622400; SameSite=None; Secure"; var googletag = googletag || { cmd: [] }; googletag.cmd.push(function () { googletag.pubads().setPublisherProvidedId(userId); googletag.enableServices(); }); window.dataLayer.push({ bmj_uuid: bmj_uuid, }); </script> </head><body><div class="section data-availability" id="sec-29"><p id="p-45">Data are available in a public, open access repository.</p></div></body></html></section></div><div class="wrap-urls mb-6"><p data-testid="ethics-title" class="mb-4 text-base font-bold">Ethics statements</p><section class="m-0 mt-2"><section data-testid="ethics-consent-section" class="mb-[16px]">Patient consent for publication: <span data-testid="ethics-consent-text" class="font-bold"><p id="p-46" class="ethics-consent-to-publish">Not applicable.</p></span></section><section data-testid="ethics-approval-section" class="m-0">Ethics approval: <span data-testid="ethics-approval-text" class="m-0 font-bold"><p id="p-47" class="ethics-approval">All animal experiment procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC), Fudan University, Shanghai, China.</p></span></section></section></div><div class="wrap-urls mb-6"><p data-testid="acknowledgements-title" class="m-0 mb-4 text-base font-bold">Acknowledgements</p><section data-testid="acknowledgements-text" class="[&_a]:text-bmj-blue-600 [&_a]:hover:text-bmj-blue-700 [&_a]:active:text-bmj-blue-800 [&_a]:focus:text-bmj-silver-800 [&_a]:focus-visible:border-bmj-silver-500 m-0 [&_a]:outline-none [&_a]:focus-visible:rounded-md [&_a]:focus-visible:border-[1px]"><html><head><script> window.dataLayer = window.dataLayer || []; function parseCookies() { let cookieHeader = document.cookie || ""; let cookies = Object.fromEntries( cookieHeader.split("; ").map((c) => c.split("=")) ); for (let key in cookies) { if (cookies[key] === "undefined") { cookies[key] = undefined; } } return cookies; } function uuidv4() { var d = new Date().getTime(); //Timestamp var d2 = (typeof performance !== "undefined" && performance.now && performance.now() * 1000) || 0; //Time in microseconds since page-load or 0 if unsupported return "xxxxxxxx-xxxx-4xxx-yxxx-xxxxxxxxxxxx".replace(/[xy]/g, function (c) { var r = Math.random() * 16; //random number between 0 and 16 if (d > 0) { //Use timestamp until depleted r = (d + r) % 16 | 0; d = Math.floor(d / 16); } else { //Use microseconds since page-load if supported r = (d2 + r) % 16 | 0; d2 = Math.floor(d2 / 16); } return (c === "x" ? r : (r & 0x3) | 0x8).toString(16); }); } function handleCookie() { let cookies = parseCookies(); let bmj_uuid = cookies.bmj_uuid; if (!bmj_uuid) { bmj_uuid = uuidv4(); cookies.bmj_uuid = bmj_uuid; } return { bmj_uuid }; } let { bmj_uuid } = handleCookie(); let bmj_ppid = parseCookies().bmj_ppid; const anonMailId = "e3b0c44298fc1c149afbf4c8996fb92427ae41e4649b934ca495991b7852b855"; let nonAnonMailId = window.dataLayer.find((item) => item.user)?.user?.mail === anonMailId ? null : window.dataLayer.find((item) => item.user)?.user?.mail; let userId = dataLayer.find((item) => item.user)?.user?.["data-ics"] ?? (dataLayer.find((item) => item.user)?.user?.mail && nonAnonMailId) ?? bmj_ppid ?? bmj_uuid; document.cookie = "bmj_ppid=" + userId + "; domain=.bmj.com; path=/; max-age=31622400; SameSite=None; Secure"; document.cookie = "bmj_uuid=" + bmj_uuid + "; domain=.bmj.com; path=/; max-age=31622400; SameSite=None; Secure"; var googletag = googletag || { cmd: [] }; googletag.cmd.push(function () { googletag.pubads().setPublisherProvidedId(userId); googletag.enableServices(); }); window.dataLayer.push({ bmj_uuid: bmj_uuid, }); </script> </head><body><div class="section ack" id="ack-1"><p id="p-39">We are especially thankful to all the members of Yang Lab, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University for the aid they offered in this study.</p></div></body></html></section></div></div></div><button data-testid="back-to-top-button" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 focus-visible:border-bmj-silver-500 mt-[16px] rounded-md focus-visible:border-[1px] focus-visible:outline-none">Back to top</button></div></div></div></div></section></section><section class="section ref-list order-1" id="ref-list-1"><section data-testid="reference-list" id="ref-list-1"><div class="wrap-urls accordion-wrapper border-bmj-silver-50 border-t"><button type="button" tabindex="0" class="text-bmj-blue-800 my-[24px] flex w-full items-center justify-between text-left text-[28px] font-normal leading-10 md:text-[34px]" data-testid="accordion-toggle-button"><span data-testid="accordion-title">References</span><img class="m-0" src="/next-resources/AccordionArrowDown.svg" alt="Open accordion" /></button><div class="mt-2 pb-[24px] hidden" data-testid="accordion-content"><ol class="m-0 list-decimal" data-testid="reference-list-ol"><li data-testid="reference-item-ref-1"><div class="my-4 flex items-center" id="ref-1"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-1-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">van der Flier WM, </span><span class="text-bmj-silver-800" data-testid="author-1">Skoog I, </span><span class="text-bmj-silver-800" data-testid="author-2">Schneider JA, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Vascular cognitive impairment. </span><span class="text-bmj-silver-800"><span>Nat Rev Dis Primers</span> <span>2018; </span><span>4:18003</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1038/nrdp.2018.3" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1038/nrdp.2018.3<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Vascular cognitive impairment" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/29446769/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-2"><div class="my-4 flex items-center" id="ref-2"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-1-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Skrobot OA, </span><span class="text-bmj-silver-800" data-testid="author-1">Attems J, </span><span class="text-bmj-silver-800" data-testid="author-2">Esiri M, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment. </span><span class="text-bmj-silver-800"><span>Brain</span> <span>2016; </span><span>139:2957–69</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1093/brain/aww214" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1093/brain/aww214<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/27591113/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-3"><div class="my-4 flex items-center" id="ref-3"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-3-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Román GC, </span><span class="text-bmj-silver-800" data-testid="author-1">Tatemichi TK, </span><span class="text-bmj-silver-800" data-testid="author-2">Erkinjuntti T, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. </span><span class="text-bmj-silver-800"><span>Neurology</span> <span>1993; </span><span>43:250–60</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1212/WNL.43.2.250" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1212/WNL.43.2.250<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/8094895/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-4"><div class="my-4 flex items-center" id="ref-4"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-3-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Kalaria RN. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">The pathology and pathophysiology of vascular dementia. </span><span class="text-bmj-silver-800"><span>Neuropharmacology</span> <span>2018; </span><span>134:226–39</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/j.neuropharm.2017.12.030" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/j.neuropharm.2017.12.030<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=The pathology and pathophysiology of vascular dementia" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/29273521/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-5"><div class="my-4 flex items-center" id="ref-5"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-5-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Iadecola C. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">The pathobiology of vascular dementia. </span><span class="text-bmj-silver-800"><span>Neuron</span> <span>2013; </span><span>80:844–66</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/j.neuron.2013.10.008" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/j.neuron.2013.10.008<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=The pathobiology of vascular dementia" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/24267647/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-6"><div class="my-4 flex items-center" id="ref-6"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-5-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Snyder HM, </span><span class="text-bmj-silver-800" data-testid="author-1">Corriveau RA, </span><span class="text-bmj-silver-800" data-testid="author-2">Craft S, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Vascular contributions to cognitive impairment and dementia including Alzheimer's disease. </span><span class="text-bmj-silver-800"><span>Alzheimers Dement</span> <span>2015; </span><span>11:710–7</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/j.jalz.2014.10.008" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/j.jalz.2014.10.008<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Vascular contributions to cognitive impairment and dementia including Alzheimer's disease" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/25510382/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-7"><div class="my-4 flex items-center" id="ref-7"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-7-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Yang Y, </span><span class="text-bmj-silver-800" data-testid="author-1">Kimura-Ohba S, </span><span class="text-bmj-silver-800" data-testid="author-2">Thompson J, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Rodent models of vascular cognitive impairment. </span><span class="text-bmj-silver-800"><span>Transl Stroke Res</span> <span>2016; </span><span>7:407–14</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1007/s12975-016-0486-2" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1007/s12975-016-0486-2<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Rodent models of vascular cognitive impairment" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/27498679/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-8"><div class="my-4 flex items-center" id="ref-8"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-7-2" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Tuo Q-zhang, </span><span class="text-bmj-silver-800" data-testid="author-1">Zou J-jun, </span><span class="text-bmj-silver-800" data-testid="author-2">Lei P, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Rodent models of vascular cognitive impairment. </span><span class="text-bmj-silver-800"><span>J Mol Neurosci</span> <span>2021; </span><span>71:1–12</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1007/s12031-020-01733-2" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1007/s12031-020-01733-2<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Rodent models of vascular cognitive impairment" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a></section></div></li><li data-testid="reference-item-ref-9"><div class="my-4 flex items-center" id="ref-9"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-9-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Madigan JB, </span><span class="text-bmj-silver-800" data-testid="author-1">Wilcock DM, </span><span class="text-bmj-silver-800" data-testid="author-2">Hainsworth AH, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Vascular contributions to cognitive impairment and dementia: topical review of animal models. </span><span class="text-bmj-silver-800"><span>Stroke</span> <span>2016; </span><span>47:1953–9</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1161/STROKEAHA.116.012066" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1161/STROKEAHA.116.012066<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Vascular contributions to cognitive impairment and dementia: topical review of animal models" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/27301939/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-10"><div class="my-4 flex items-center" id="ref-10"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-10-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Duncombe J, </span><span class="text-bmj-silver-800" data-testid="author-1">Kitamura A, </span><span class="text-bmj-silver-800" data-testid="author-2">Hase Y, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. closing the translational gap between rodent models and human vascular cognitive impairment and dementia. </span><span class="text-bmj-silver-800"><span>Clin Sci</span> <span>2017; </span><span>131:2451–68</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1042/CS20160727" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1042/CS20160727<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. closing the translational gap between rodent models and human vascular cognitive impairment and dementia" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/28963120/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-11"><div class="my-4 flex items-center" id="ref-11"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-11-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Barone FC, </span><span class="text-bmj-silver-800" data-testid="author-1">Knudsen DJ, </span><span class="text-bmj-silver-800" data-testid="author-2">Nelson AH, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Mouse strain differences in susceptibility to cerebral ischemia are related to cerebral vascular anatomy. </span><span class="text-bmj-silver-800"><span>J Cereb Blood Flow Metab</span> <span>1993; </span><span>13:683–92</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1038/jcbfm.1993.87" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1038/jcbfm.1993.87<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Mouse strain differences in susceptibility to cerebral ischemia are related to cerebral vascular anatomy" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/8314921/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-12"><div class="my-4 flex items-center" id="ref-12"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-12-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Song Y, </span><span class="text-bmj-silver-800" data-testid="author-1">Li Z, </span><span class="text-bmj-silver-800" data-testid="author-2">He T, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124. </span><span class="text-bmj-silver-800"><span>Theranostics</span> <span>2019; </span><span>9:2910–23</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.7150/thno.30879" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.7150/thno.30879<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/31244932/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-13"><div class="my-4 flex items-center" id="ref-13"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-13-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Wang J, </span><span class="text-bmj-silver-800" data-testid="author-1">Lin X, </span><span class="text-bmj-silver-800" data-testid="author-2">Mu Z, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Rapamycin increases collateral circulation in rodent brain after focal ischemia as detected by multiple modality dynamic imaging. </span><span class="text-bmj-silver-800"><span>Theranostics</span> <span>2019; </span><span>9:4923–34</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.7150/thno.32676" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.7150/thno.32676<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Rapamycin increases collateral circulation in rodent brain after focal ischemia as detected by multiple modality dynamic imaging" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/31410191/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-14"><div class="my-4 flex items-center" id="ref-14"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-14-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Vorhees CV, </span><span class="text-bmj-silver-800" data-testid="author-1">Williams MT. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Morris water maze: procedures for assessing spatial and related forms of learning and memory. </span><span class="text-bmj-silver-800"><span>Nat Protoc</span> <span>2006; </span><span>1:848–58</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1038/nprot.2006.116" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1038/nprot.2006.116<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Morris water maze: procedures for assessing spatial and related forms of learning and memory" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/17406317/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-15"><div class="my-4 flex items-center" id="ref-15"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-9-2" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Hodges H, </span><span class="text-bmj-silver-800" data-testid="author-1">Nelson A, </span><span class="text-bmj-silver-800" data-testid="author-2">Virley D, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Cognitive deficits induced by global cerebral ischaemia: prospects for transplant therapy. </span><span class="text-bmj-silver-800"><span>Pharmacol Biochem Behav</span> <span>1997; </span><span>56:763–80</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/S0091-3057(96)00424-8" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/S0091-3057(96)00424-8<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Cognitive deficits induced by global cerebral ischaemia: prospects for transplant therapy" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/9130304/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-16"><div class="my-4 flex items-center" id="ref-16"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-16-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">León-Moreno LC, </span><span class="text-bmj-silver-800" data-testid="author-1">Castañeda-Arellano R, </span><span class="text-bmj-silver-800" data-testid="author-2">Rivas-Carrillo JD, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Challenges and improvements of developing an ischemia mouse model through bilateral common carotid artery occlusion. </span><span class="text-bmj-silver-800"><span>J Stroke Cerebrovasc Dis</span> <span>2020; </span><span>29:104773</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104773" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/j.jstrokecerebrovasdis.2020.104773<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Challenges and improvements of developing an ischemia mouse model through bilateral common carotid artery occlusion" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/32199775/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-17"><div class="my-4 flex items-center" id="ref-17"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-5-2" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Min L-J, </span><span class="text-bmj-silver-800" data-testid="author-1">Iwanami J, </span><span class="text-bmj-silver-800" data-testid="author-2">Shudou M, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Deterioration of cognitive function after transient cerebral ischemia with amyloid-β infusion-possible amelioration of cognitive function by AT2 receptor activation. </span><span class="text-bmj-silver-800"><span>J Neuroinflammation</span> <span>2020; </span>17. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1186/s12974-020-01775-8" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1186/s12974-020-01775-8<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Deterioration of cognitive function after transient cerebral ischemia with amyloid-β infusion-possible amelioration of cognitive function by AT2 receptor activation" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/32264971/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-18"><div class="my-4 flex items-center" id="ref-18"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-5-2" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Li W, </span><span class="text-bmj-silver-800" data-testid="author-1">Huang R, </span><span class="text-bmj-silver-800" data-testid="author-2">Shetty RA, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model. </span><span class="text-bmj-silver-800"><span>Neurobiol Dis</span> <span>2013; </span><span>59:18–25</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/j.nbd.2013.06.014" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/j.nbd.2013.06.014<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/23845275/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-19"><div class="my-4 flex items-center" id="ref-19"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-19-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Hermawati E, </span><span class="text-bmj-silver-800" data-testid="author-1">Arfian N, </span><span class="text-bmj-silver-800" data-testid="author-2">Partadiredja G, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Spatial memory disturbance following transient brain ischemia is associated with vascular remodeling in hippocampus. </span><span class="text-bmj-silver-800"><span>Kobe J Med Sci</span> <span>2018; </span><span>64:E93–106</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="https://scholar.google.com/scholar?q=Spatial memory disturbance following transient brain ischemia is associated with vascular remodeling in hippocampus" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/30666039/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-20"><div class="my-4 flex items-center" id="ref-20"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-20-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Beason-Held LL, </span><span class="text-bmj-silver-800" data-testid="author-1">Moghekar A, </span><span class="text-bmj-silver-800" data-testid="author-2">Zonderman AB, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Longitudinal changes in cerebral blood flow in the older hypertensive brain. </span><span class="text-bmj-silver-800"><span>Stroke</span> <span>2007; </span><span>38:1766–73</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1161/STROKEAHA.106.477109" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1161/STROKEAHA.106.477109<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Longitudinal changes in cerebral blood flow in the older hypertensive brain" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/17510458/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-21"><div class="my-4 flex items-center" id="ref-21"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-21-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Yoshizaki K, </span><span class="text-bmj-silver-800" data-testid="author-1">Adachi K, </span><span class="text-bmj-silver-800" data-testid="author-2">Kataoka S, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice. </span><span class="text-bmj-silver-800"><span>Exp Neurol</span> <span>2008; </span><span>210:585–91</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/j.expneurol.2007.12.005" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/j.expneurol.2007.12.005<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/18222425/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-22"><div class="my-4 flex items-center" id="ref-22"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-22-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Chai X, </span><span class="text-bmj-silver-800" data-testid="author-1">Li X, </span><span class="text-bmj-silver-800" data-testid="author-2">Zhang W, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Legumain knockout improved cognitive impairment via reducing neuroinflammation in right unilateral common carotid artery occlusion mice. </span><span class="text-bmj-silver-800"><span>Life Sci</span> <span>2021; </span>285. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/j.lfs.2021.119944" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/j.lfs.2021.119944<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Legumain knockout improved cognitive impairment via reducing neuroinflammation in right unilateral common carotid artery occlusion mice" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/34509465/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-23"><div class="my-4 flex items-center" id="ref-23"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-22-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Zhou Y, </span><span class="text-bmj-silver-800" data-testid="author-1">Zhang J, </span><span class="text-bmj-silver-800" data-testid="author-2">Wang L, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Interleukin-1β impedes oligodendrocyte progenitor cell recruitment and white matter repair following chronic cerebral hypoperfusion. </span><span class="text-bmj-silver-800"><span>Brain Behav Immun</span> <span>2017; </span><span>60:93–105</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/j.bbi.2016.09.024" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/j.bbi.2016.09.024<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Interleukin-1β impedes oligodendrocyte progenitor cell recruitment and white matter repair following chronic cerebral hypoperfusion" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/27663285/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-24"><div class="my-4 flex items-center" id="ref-24"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-24-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Shibata M, </span><span class="text-bmj-silver-800" data-testid="author-1">Ohtani R, </span><span class="text-bmj-silver-800" data-testid="author-2">Ihara M, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. </span><span class="text-bmj-silver-800"><span>Stroke</span> <span>2004; </span><span>35:2598–603</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1161/01.STR.0000143725.19053.60" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1161/01.STR.0000143725.19053.60<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/15472111/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-25"><div class="my-4 flex items-center" id="ref-25"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-25-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Bink DI, </span><span class="text-bmj-silver-800" data-testid="author-1">Ritz K, </span><span class="text-bmj-silver-800" data-testid="author-2">Aronica E, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition. </span><span class="text-bmj-silver-800"><span>J Cereb Blood Flow Metab</span> <span>2013; </span><span>33:1666–84</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1038/jcbfm.2013.140" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1038/jcbfm.2013.140<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/23963364/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-26"><div class="my-4 flex items-center" id="ref-26"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-25-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Poh L, </span><span class="text-bmj-silver-800" data-testid="author-1">Fann DY, </span><span class="text-bmj-silver-800" data-testid="author-2">Wong P, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Aim2 inflammasome mediates hallmark neuropathological alterations and cognitive impairment in a mouse model of vascular dementia. </span><span class="text-bmj-silver-800"><span>Mol Psychiatry</span> <span>2021; </span><span>26:4544–60</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1038/s41380-020-00971-5" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1038/s41380-020-00971-5<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Aim2 inflammasome mediates hallmark neuropathological alterations and cognitive impairment in a mouse model of vascular dementia" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/33299135/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-27"><div class="my-4 flex items-center" id="ref-27"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-27-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Nishio K, </span><span class="text-bmj-silver-800" data-testid="author-1">Ihara M, </span><span class="text-bmj-silver-800" data-testid="author-2">Yamasaki N, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">A mouse model characterizing features of vascular dementia with hippocampal atrophy. </span><span class="text-bmj-silver-800"><span>Stroke</span> <span>2010; </span><span>41:1278–84</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1161/STROKEAHA.110.581686" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1161/STROKEAHA.110.581686<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=A mouse model characterizing features of vascular dementia with hippocampal atrophy" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/20448204/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-28"><div class="my-4 flex items-center" id="ref-28"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-27-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Ihara M, </span><span class="text-bmj-silver-800" data-testid="author-1">Tomimoto H. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Lessons from a mouse model characterizing features of vascular cognitive impairment with white matter changes. </span><span class="text-bmj-silver-800"><span>J Aging Res</span> <span>2011; </span><span>2011:1–11</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.4061/2011/978761" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.4061/2011/978761<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Lessons from a mouse model characterizing features of vascular cognitive impairment with white matter changes" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/22132331/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-29"><div class="my-4 flex items-center" id="ref-29"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-24-3" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">An L, </span><span class="text-bmj-silver-800" data-testid="author-1">Chopp M, </span><span class="text-bmj-silver-800" data-testid="author-2">Zacharek A, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Cardiac dysfunction in a mouse vascular dementia model of bilateral common carotid artery stenosis. </span><span class="text-bmj-silver-800"><span>Front Cardiovasc Med</span> <span>2021; </span>8. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.3389/fcvm.2021.681572" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.3389/fcvm.2021.681572<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Cardiac dysfunction in a mouse vascular dementia model of bilateral common carotid artery stenosis" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a></section></div></li><li data-testid="reference-item-ref-30"><div class="my-4 flex items-center" id="ref-30"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-24-3" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Liu Q, </span><span class="text-bmj-silver-800" data-testid="author-1">Shkirkova K, </span><span class="text-bmj-silver-800" data-testid="author-2">Lamorie-Foote K, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Air pollution particulate matter exposure and chronic cerebral hypoperfusion and measures of white matter injury in a murine model. </span><span class="text-bmj-silver-800"><span>Environ Health Perspect</span> <span>2021; </span>129. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1289/EHP8792" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1289/EHP8792<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Air pollution particulate matter exposure and chronic cerebral hypoperfusion and measures of white matter injury in a murine model" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/34424052/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-31"><div class="my-4 flex items-center" id="ref-31"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-24-3" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Xie Y, </span><span class="text-bmj-silver-800" data-testid="author-1">Zhang X, </span><span class="text-bmj-silver-800" data-testid="author-2">Xu P, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Aberrant oligodendroglial LDL receptor orchestrates demyelination in chronic cerebral ischemia. </span><span class="text-bmj-silver-800"><span>J Clin Invest</span> <span>2021; </span>131. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1172/JCI128114" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1172/JCI128114<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Aberrant oligodendroglial LDL receptor orchestrates demyelination in chronic cerebral ischemia" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/33141760/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-32"><div class="my-4 flex items-center" id="ref-32"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-32-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Chen Z, </span><span class="text-bmj-silver-800" data-testid="author-1">Venkat P, </span><span class="text-bmj-silver-800" data-testid="author-2">Seyfried D, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Brain-Heart interaction: cardiac complications after stroke. </span><span class="text-bmj-silver-800"><span>Circ Res</span> <span>2017; </span><span>121:451–68</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1161/CIRCRESAHA.117.311170" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1161/CIRCRESAHA.117.311170<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Brain-Heart interaction: cardiac complications after stroke" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/28775014/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-33"><div class="my-4 flex items-center" id="ref-33"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-20-2" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Gorelick PB, </span><span class="text-bmj-silver-800" data-testid="author-1">Counts SE, </span><span class="text-bmj-silver-800" data-testid="author-2">Nyenhuis D, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Vascular cognitive impairment and dementia. </span><span class="text-bmj-silver-800"><span>Biochim Biophys Acta</span> <span>2016; </span><span>1862:860–8</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/j.bbadis.2015.12.015" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/j.bbadis.2015.12.015<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Vascular cognitive impairment and dementia" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/26704177/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-34"><div class="my-4 flex items-center" id="ref-34"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-34-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Kapadia M, </span><span class="text-bmj-silver-800" data-testid="author-1">Xu J, </span><span class="text-bmj-silver-800" data-testid="author-2">Sakic B, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">The water maze paradigm in experimental studies of chronic cognitive disorders: theory, protocols, analysis, and inference. </span><span class="text-bmj-silver-800"><span>Neurosci Biobehav Rev</span> <span>2016; </span><span>68:195–217</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/j.neubiorev.2016.05.016" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/j.neubiorev.2016.05.016<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=The water maze paradigm in experimental studies of chronic cognitive disorders: theory, protocols, analysis, and inference" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/27229758/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-35"><div class="my-4 flex items-center" id="ref-35"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-35-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Tucker LB, </span><span class="text-bmj-silver-800" data-testid="author-1">Velosky AG, </span><span class="text-bmj-silver-800" data-testid="author-2">McCabe JT, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Applications of the Morris water maze in translational traumatic brain injury research. </span><span class="text-bmj-silver-800"><span>Neurosci Biobehav Rev</span> <span>2018; </span><span>88:187–200</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/j.neubiorev.2018.03.010" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/j.neubiorev.2018.03.010<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Applications of the Morris water maze in translational traumatic brain injury research" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/29545166/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-36"><div class="my-4 flex items-center" id="ref-36"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-35-1" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Conrad CD. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">A critical review of chronic stress effects on spatial learning and memory. </span><span class="text-bmj-silver-800"><span>Prog Neuropsychopharmacol Biol Psychiatry</span> <span>2010; </span><span>34:742–55</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1016/j.pnpbp.2009.11.003" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1016/j.pnpbp.2009.11.003<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=A critical review of chronic stress effects on spatial learning and memory" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/19903505/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li><li data-testid="reference-item-ref-37"><div class="my-4 flex items-center" id="ref-37"><section class="relative pl-[25px] leading-[24px]"><span class="absolute left-0 h-100"><a href="#xref-ref-7-3" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]" data-testid="reference-link"><img src="/next-resources/circle-arrow-up.svg" alt="close" class="inline h-4 mt-1" data-testid="citation-arrow-img" /></a> </span><span class="text-bmj-silver-800" data-testid="author-0">Tuo Q-Z, </span><span class="text-bmj-silver-800" data-testid="author-1">Zou J-J, </span><span class="text-bmj-silver-800" data-testid="author-2">Lei P, </span><span data-testid="authors-etal" class="text-bmj-silver-800">et al. </span><span class="text-bmj-silver-800 wrap-urls" data-testid="reference-title">Rodent models of vascular cognitive impairment. </span><span class="text-bmj-silver-800"><span>J Mol Neurosci</span> <span>2021; </span><span>71:1–12</span>. </span><div class="inline" data-testid="available-link-container"></div><a href="http://dx.doi.org/10.1007/s12031-020-01733-2" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell" data-testid="link-doi">doi:10.1007/s12031-020-01733-2<span class="link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span></a><a href="https://scholar.google.com/scholar?q=Rodent models of vascular cognitive impairment" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-google-scholar">Google Scholar</a><a href="https://pubmed.ncbi.nlm.nih.gov/33107013/" target="_blank" rel="noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell" data-testid="link-pubmed"><span class="link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]">•</span>PubMed</a></section></div></li></ol><button data-testid="back-to-top-button" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 focus-visible:border-bmj-silver-500 mt-[16px] rounded-md focus-visible:border-[1px] focus-visible:outline-none">Back to top</button></div></div></section></section></div><section class="mt-6" id="history-list"><div class="wrap-urls accordion-wrapper border-bmj-silver-50 border-t"><button type="button" tabindex="0" class="text-bmj-blue-800 my-[24px] flex w-full items-center justify-between text-left text-[28px] font-normal leading-10 md:text-[34px]" data-testid="accordion-toggle-button"><span data-testid="accordion-title">Publication history</span><img class="m-0" src="/next-resources/AccordionArrowDown.svg" alt="Open accordion" /></button><div class="mt-2 pb-[24px] hidden" data-testid="accordion-content"><section aria-labelledby="publication-history-heading" data-testid="publication-history"><ul class="text-bmj-silver-800 m-0 mb-2 list-none p-0"><li class="m-0 p-0 pb-0.5" data-testid="date-entry-received">Received: <strong>4 April 2022</strong></li><li class="m-0 p-0 pb-0.5" data-testid="date-entry-accepted">Accepted: <strong>11 May 2022</strong></li><li class="m-0 p-0 pb-0.5" data-testid="date-entry-first published">First Published: <strong>20 December 2022</strong></li></ul><div data-testid="links-container"></div></section><h3 class="m-0 p-0">Article Versions</h3><ul class="m-0 p-0"><li class="m-0 list-none p-0"><a href="/content/early/2022/07/11/svn-2022-001594" rel="noopener noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell underline hover:decoration-2 hover:underline-offset-2">Earlier version - 11 July 2022</a></li><li class="m-0 list-none p-0"><a href="/content/early/2022/07/13/svn-2022-001594" rel="noopener noreferrer" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell underline hover:decoration-2 hover:underline-offset-2">Earlier version - 14 July 2022</a></li><li class="m-0 list-none p-0">You are viewing the most recent version of this article - 20 December 2022</li></ul><button data-testid="back-to-top-button" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 focus-visible:border-bmj-silver-500 mt-[16px] rounded-md focus-visible:border-[1px] focus-visible:outline-none">Back to top</button></div></div></section><section id="rapid-responses" class="article mt-6"><div class="wrap-urls accordion-wrapper border-bmj-silver-50 border-b border-t"><button type="button" tabindex="0" class="text-bmj-blue-800 my-[24px] flex w-full items-center justify-between text-left text-[28px] font-normal leading-10 md:text-[34px]" data-testid="accordion-toggle-button"><span data-testid="accordion-title">Rapid Responses</span><img class="m-0" src="/next-resources/AccordionArrowDown.svg" alt="Open accordion" /></button><div class="mt-2 pb-[24px] hidden" data-testid="accordion-content"><div data-testid="compose-rapid-response" class="mb-6"><a href="/content/7/6/527/rapid-responses" target="_blank" rel="noreferrer" class="text-bmj-blue-600 focus:text-bmj-blue-800 hover:text-bmj-blue-700 font-bold !no-underline"><span class="flex items-center">Compose a Response to This Article<svg class="ml-1 mb-[2px]" width="20" height="20" viewBox="0 0 20 20" fill="none" xmlns="http://www.w3.org/2000/svg"><path d="M9.99984 4.1665V15.8332M4.1665 9.99984H15.8332" stroke="#2663A8" stroke-width="1.5" stroke-linecap="round" stroke-linejoin="round"></path></svg></span></a></div><div data-testid="rapid-responses-list"></div><button data-testid="back-to-top-button" class="visible-link text-bmj-blue-600 hover:text-bmj-blue-700 focus-visible:border-bmj-silver-500 mt-[16px] rounded-md focus-visible:border-[1px] focus-visible:outline-none">Back to top</button></div></div></section></div></div><div class="SidebarBox border-bmj-silver-50 col-span-2 overflow-y-auto border-t pr-4 lg:sticky lg:top-[45px] lg:col-span-1 lg:h-screen lg:border-none lg:pl-2 lg:pt-4"><div data-testid="overview" class="wrap-urls mt-0 hidden pb-4 lg:my-6 lg:block"><p data-testid="overview-title" class="text-bmj-silver-800 m-0 mb-4 pt-6 text-xl font-bold lg:pt-0">Overview</p><ul class="m-0 list-none p-0" data-testid="overview-list"><li class="mx-0 pl-0 hidden lg:block"><a href="#abstract-1" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline" data-testid="overview-list-1">Abstract</a></li><li class="mx-0 pl-0 hidden lg:block"><a href="#sec-8" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline" data-testid="overview-list-2">Introduction</a></li><li class="mx-0 pl-0 hidden lg:block"><a href="#sec-9" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline" data-testid="overview-list-3">Materials and methods</a></li><li class="mx-0 pl-0 hidden lg:block"><a href="#sec-21" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline" data-testid="overview-list-4">Results</a></li><li class="mx-0 pl-0 hidden lg:block"><a href="#sec-28" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline" data-testid="overview-list-5">Discussion</a></li><li class="mx-0 pl-0 hidden lg:block"><a href="#ref-list-1" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline" data-testid="overview-list-6">References</a></li><div data-testid="overview-divider" class="my-6 w-[50%] border border-[#c6c6c9]"></div><li class="mx-0 pl-0 hidden lg:block"><a href="#fn-group-1" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline" data-testid="overview-list-7">Footnotes</a></li><li class="mx-0 pl-0 hidden lg:block"><a href="#history-list" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline" data-testid="overview-list-8">Publication history</a></li><li class="mx-0 pl-0 hidden lg:block"><a href="#rapid-responses" class="text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline" data-testid="overview-list-9">Rapid Responses</a></li></ul></div><main class="flex flex-col pt-6 lg:pt-0" data-testid="metrics-container"><strong class="text-bmj-silver-800 mb-4 text-xl">Article metrics</strong><section data-testid="altmetric-link-container" class="flex flex-row items-center justify-between"><a class="hover:text-bmj-blue-700 text-bmj-blue-600 flex items-center justify-between text-base no-underline" href="https://www.altmetric.com/details.php?citation_id=132174841" target="_blank" rel="noopener noreferrer" data-testid="altmetric-link">Altmetric<img id="open-url-icon-for-metrics" class="m-0 ml-2 h-[14px] w-[14px] p-0" src="/next-resources/open-url-for-metrics.svg" alt="open-url" data-testid="altmetric-icon" /></a></section><section data-testid="dimensions-link-container" class="flex flex-row items-center justify-between pb-[1.5rem]"><a class="hover:text-bmj-blue-700 text-bmj-blue-600 flex items-center justify-between text-base no-underline" href="https://badge.dimensions.ai/details/doi/10.1136/svn-2022-001594?domain=10.1136/svn-2022-001594" target="_blank" rel="noopener noreferrer" data-testid="dimensions-link">Dimensions<img id="open-url-icon-for-metrics" class="m-0 ml-2 h-[14px] w-[14px] p-0" src="/next-resources/open-url-for-metrics.svg" alt="open-url" data-testid="dimensions-icon" /></a></section></main><div class="undefined flex items-center justify-center py-3 undefined undefined"><div id="div-gpt-ad-1686906823508-0" data-testid="middle-ad-slot" class="flex items-center justify-center w-[300px] h-[250px] md:h-[600px]"></div></div></div></div></div></div></div></main></div></div><footer><div class="border-bmj-silver-100 border-t-solid m-0 ml-auto mr-auto flex w-full min-w-0 flex-wrap gap-4 border border-b-0 border-l-0 border-r-0 pl-4 pr-4"><a class="my-4" href="http://www.chinastroke.net/" data-testid="association-logo-1-link" aria-label="Chinese Stroke Association"><img data-testid="association-logo-1" title="Chinese Stroke Association" alt="Chinese Stroke Association" loading="lazy" width="93" height="90" decoding="async" data-nimg="1" style="color:transparent" srcSet="/_next/image?url=https%3A%2F%2Fsvn.bmj.com%2Fsvn%2Fwp-content%2Fuploads%2Fsites%2F57%2F2023%2F04%2Fsociety-logo-csa.png&w=96&q=75 1x, /_next/image?url=https%3A%2F%2Fsvn.bmj.com%2Fsvn%2Fwp-content%2Fuploads%2Fsites%2F57%2F2023%2F04%2Fsociety-logo-csa.png&w=256&q=75 2x" src="/_next/image?url=https%3A%2F%2Fsvn.bmj.com%2Fsvn%2Fwp-content%2Fuploads%2Fsites%2F57%2F2023%2F04%2Fsociety-logo-csa.png&w=256&q=75" /></a></div><div class="bg-bmj-primary-brand text-bmj-white m-0 mx-auto flex w-full min-w-0 flex-col px-4 md:flex-row"><div data-testid="footer-content" class="md:border-b-none [&:last-child]:border-b-none m-0 ml-auto mr-auto w-full min-w-0 border-b-[1px] border-b-white/50 pr-6 pt-5 pb-4 md:pt-8 md:pb-8"><span class="mt-0 mb-5 block text-base font-normal uppercase leading-4">CONTENT</span><ul class="ml-0 mb-4 pl-0"><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/content/early/recent">Latest content</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/content/current">Current issue</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/pages/top-cited-articles/">Top cited articles</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/pages/most-read-articles/">Most Read Articles</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/content/by/year">Archive</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/pages/browse-by-collection/">Browse by collection</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/eletters">Responses</a></li></ul><div class="flex"><a href="/pages/rss-feeds" data-testid="rss" class="[&>img]:m-[2px] [&>img]:p-[4px] [&>img]:hover:bg-white/20"><img src="https://resources.bmj.com/repository/journals-network-project/images/social-media/rss.svg" alt="rss-icon" width="35" height="35" /></a><a href="https://twitter.com/SVN_BMJ" data-testid="x" class="[&>img]:m-[2px] [&>img]:p-[4px] [&>img]:hover:bg-white/20"><img src="https://resources.bmj.com/repository/journals-network-project/images/social-media/x.svg" alt="x-icon" width="35" height="35" /></a></div></div><div data-testid="footer-journal" class="md:border-b-none [&:last-child]:border-b-none m-0 ml-auto mr-auto w-full min-w-0 border-b-[1px] border-b-white/50 pr-6 pt-5 pb-4 md:pt-8 md:pb-8"><span class="mt-0 mb-5 block text-base font-normal uppercase leading-4">JOURNAL</span><ul class="ml-0 mb-4 pl-0"><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/pages/about/">About</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/pages/editorial-board/">Editorial board</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/pages/thank-you-to-our-reviewers/">Thank you to our reviewers</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="https://myaccount.bmj.com/myaccount/signup.html?regService=etoc-alerts&corpusCode=svnbmj&fwdUrl=https://svn.bmj.com">Sign up for email alerts</a></li></ul><div class="flex"></div></div><div data-testid="footer-authors" class="md:border-b-none [&:last-child]:border-b-none m-0 ml-auto mr-auto w-full min-w-0 border-b-[1px] border-b-white/50 pr-6 pt-5 pb-4 md:pt-8 md:pb-8"><span class="mt-0 mb-5 block text-base font-normal uppercase leading-4">AUTHORS</span><ul class="ml-0 mb-4 pl-0"><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/pages/authors/">Instructions for authors</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="https://mc.manuscriptcentral.com/svn">Submit an article</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="https://authors.bmj.com/policies/">Editorial policies</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/pages/faqs/">FAQs</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="https://openaccess.bmj.com/">Open access at BMJ</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="https://authors.bmj.com/">BMJ Author Hub</a></li></ul><div class="flex"></div></div><div data-testid="footer-help" class="md:border-b-none [&:last-child]:border-b-none m-0 ml-auto mr-auto w-full min-w-0 border-b-[1px] border-b-white/50 pr-6 pt-5 pb-4 md:pt-8 md:pb-8"><span class="mt-0 mb-5 block text-base font-normal uppercase leading-4">HELP</span><ul class="ml-0 mb-4 pl-0"><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="/pages/contact-us/">Contact us</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="https://journals.bmj.com/cgi/reprintform">Reprints</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="https://www.bmj.com/company/products-services/rights-and-licensing/permissions">Permissions</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="https://www.bmj.com/company/for-advertisers-and-sponsor/">Advertising</a></li><li class="mb-4 list-none leading-none [&:last-child]:mb-0"><a class="text-bmj-white leading-none no-underline [&:hover]:underline" href="https://myaccount.bmj.com/myaccount/customerservice/salesforce-form.html">Feedback form</a></li></ul><div class="flex"></div></div></div><div class="justify-normal m-0 mx-auto flex w-full min-w-0 flex-col px-4 pt-4 md:flex-row md:justify-between"><div class="relative h-[35px] w-[60px]"><a data-testid="bmj-footer-logo-link" href="https://www.bmj.com/company/"><img src="/_next/static/media/bmj-footer-logo.c6e1ad28003cb22dbd978555514ed05c.svg" alt="bmj-footer-logo" height="35" /></a></div><div data-testid="copyright-data-wrapper" class="flex flex-col items-start md:items-end [&>:first-of-type]:mt-0 [&>span:nth-of-type(2)]:whitespace-normal"><a data-testid="website-terms-and-conditions" href="https://www.bmj.com/company/legal-information/" class="decoration-none text-bmj-normal text-bmj-blue-500 [&:hover]:decoration-none [&:hover]:text-bmj-primary-brand mb-2 [&&&]:mt-2 [&&&]:md:mt-0">Website Terms & Conditions</a><a data-testid="privacy-and-cookies" href="https://www.bmj.com/company/your-privacy/" class="decoration-none text-bmj-normal text-bmj-blue-500 [&:hover]:decoration-none [&:hover]:text-bmj-primary-brand mb-2 [&&&]:mt-2 [&&&]:md:mt-0">Privacy & Cookies</a><a data-testid="contact-bmj" href="https://www.bmj.com/company/contact-us/" class="decoration-none text-bmj-normal text-bmj-blue-500 [&:hover]:decoration-none [&:hover]:text-bmj-primary-brand mb-2 [&&&]:mt-2 [&&&]:md:mt-0">Contact BMJ</a><a href="#!" data-testid="cookie-settings" id="ot-sdk-btn" class="ot-sdk-show-settings decoration-none !mt:0 mb-2 cursor-pointer !border !border-[#43791A] !bg-transparent px-2 py-1 !text-[0.875rem] !text-[#43791A] duration-100 ease-linear md:mb-0 [&:hover]:!bg-[#43791A] [&:hover]:!text-white">Cookie settings</a><span data-testid="online-issn" class="text-bmj-silver-800 whitespace-pre text-sm leading-normal [&&&]:mt-2">Online ISSN: 2059-8696</span><span data-testid="copyright" class="text-bmj-silver-800 mb-2 mt-2 whitespace-pre text-[0.875rem]">Copyright © 2024 Chinese Stroke Association. All rights reserved.</span></div></div></footer><div class="border-t-divider bg-bmj-siver-30 border-t flex items-center justify-center py-3 min-w-[auto] min-h-[100px] md:min-h-[250px]"><div id="div-gpt-ad-3321227-2" data-testid="bottom-ad-slot" class="flex items-center justify-center w-[auto] h-[100px] md:h-[250px]"></div></div></div><script src="/_next/static/chunks/webpack-8279bfe1e5fb5dfc.js" async=""></script></body></html><script>(self.__next_f=self.__next_f||[]).push([0]);self.__next_f.push([2,null])</script><script>self.__next_f.push([1,"1:HL[\"/_next/static/css/bb076035c270e51f.css\",\"style\"]\n2:HL[\"/_next/static/css/c9c0e70a6968a49d.css\",\"style\"]\n3:HL[\"/_next/static/css/66ad511738c93f8a.css\",\"style\"]\n"])</script><script>self.__next_f.push([1,"4:I[9562,[],\"\"]\n7:I[8703,[],\"\"]\nb:I[3751,[],\"\"]\ne:I[1395,[],\"\"]\n8:[\"volume\",\"7\",\"d\"]\n9:[\"issue\",\"6\",\"d\"]\na:[\"articleId\",\"527\",\"d\"]\nf:[]\n"])</script><script>self.__next_f.push([1,"0:[[[\"$\",\"link\",\"0\",{\"rel\":\"stylesheet\",\"href\":\"/_next/static/css/bb076035c270e51f.css\",\"precedence\":\"next\",\"crossOrigin\":\"$undefined\"}],[\"$\",\"link\",\"1\",{\"rel\":\"stylesheet\",\"href\":\"/_next/static/css/c9c0e70a6968a49d.css\",\"precedence\":\"next\",\"crossOrigin\":\"$undefined\"}],[\"$\",\"link\",\"2\",{\"rel\":\"stylesheet\",\"href\":\"/_next/static/css/66ad511738c93f8a.css\",\"precedence\":\"next\",\"crossOrigin\":\"$undefined\"}]],[\"$\",\"$L4\",null,{\"buildId\":\"SDy8bg_tfSL4n-HtIlVWW\",\"assetPrefix\":\"\",\"initialCanonicalUrl\":\"/content/7/6/527\",\"initialTree\":[\"\",{\"children\":[\"content\",{\"children\":[[\"volume\",\"7\",\"d\"],{\"children\":[[\"issue\",\"6\",\"d\"],{\"children\":[[\"articleId\",\"527\",\"d\"],{\"children\":[\"__PAGE__\",{}]}]}]}]}]},\"$undefined\",\"$undefined\",true],\"initialSeedData\":[\"\",{\"children\":[\"content\",{\"children\":[[\"volume\",\"7\",\"d\"],{\"children\":[[\"issue\",\"6\",\"d\"],{\"children\":[[\"articleId\",\"527\",\"d\"],{\"children\":[\"__PAGE__\",{},[[\"$L5\",\"$L6\"],null],null]},[\"$\",\"$L7\",null,{\"parallelRouterKey\":\"children\",\"segmentPath\":[\"children\",\"content\",\"children\",\"$8\",\"children\",\"$9\",\"children\",\"$a\",\"children\"],\"error\":\"$undefined\",\"errorStyles\":\"$undefined\",\"errorScripts\":\"$undefined\",\"template\":[\"$\",\"$Lb\",null,{}],\"templateStyles\":\"$undefined\",\"templateScripts\":\"$undefined\",\"notFound\":\"$undefined\",\"notFoundStyles\":\"$undefined\",\"styles\":null}],null]},[\"$\",\"$L7\",null,{\"parallelRouterKey\":\"children\",\"segmentPath\":[\"children\",\"content\",\"children\",\"$8\",\"children\",\"$9\",\"children\"],\"error\":\"$undefined\",\"errorStyles\":\"$undefined\",\"errorScripts\":\"$undefined\",\"template\":[\"$\",\"$Lb\",null,{}],\"templateStyles\":\"$undefined\",\"templateScripts\":\"$undefined\",\"notFound\":\"$undefined\",\"notFoundStyles\":\"$undefined\",\"styles\":null}],null]},[\"$\",\"$L7\",null,{\"parallelRouterKey\":\"children\",\"segmentPath\":[\"children\",\"content\",\"children\",\"$8\",\"children\"],\"error\":\"$undefined\",\"errorStyles\":\"$undefined\",\"errorScripts\":\"$undefined\",\"template\":[\"$\",\"$Lb\",null,{}],\"templateStyles\":\"$undefined\",\"templateScripts\":\"$undefined\",\"notFound\":\"$undefined\",\"notFoundStyles\":\"$undefined\",\"styles\":null}],null]},[\"$\",\"$L7\",null,{\"parallelRouterKey\":\"children\",\"segmentPath\":[\"children\",\"content\",\"children\"],\"error\":\"$undefined\",\"errorStyles\":\"$undefined\",\"errorScripts\":\"$undefined\",\"template\":[\"$\",\"$Lb\",null,{}],\"templateStyles\":\"$undefined\",\"templateScripts\":\"$undefined\",\"notFound\":\"$undefined\",\"notFoundStyles\":\"$undefined\",\"styles\":null}],null]},[\"$Lc\",null],null],\"couldBeIntercepted\":false,\"initialHead\":[false,\"$Ld\"],\"globalErrorComponent\":\"$e\",\"missingSlots\":\"$Wf\"}]]\n"])</script><script>self.__next_f.push([1,"10:I[5327,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"\"]\n11:I[3792,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"AdsScript\"]\n12:I[5097,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"Script\"]\n13:I[4087,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"PageWithMenu\"]\n14:I[37,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"619\",\"static/chunks/619-a89c76242bbf01ff.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"601\",\"static/chunks/app/error-7bbbe3d22319187d.js\"],\"default\"]\n16:I[5097,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561"])</script><script>self.__next_f.push([1,".js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"Image\"]\n"])</script><script>self.__next_f.push([1,"c:[\"$\",\"html\",null,{\"lang\":\"en\",\"children\":[[\"$\",\"head\",null,{\"children\":[[\"$\",\"link\",null,{\"rel\":\"shortcut icon\",\"href\":\"/next-resources/favicon.ico\",\"type\":\"image/vnd.microsoft.icon\"}],[\"$\",\"link\",null,{\"rel\":\"preload\",\"href\":\"https://securepubads.g.doubleclick.net/tag/js/gpt.js\",\"as\":\"script\"}],[\"$\",\"link\",null,{\"rel\":\"preconnect dns-prefetch\",\"href\":\"https://analytics.bmj.com\"}],[\"$\",\"link\",null,{\"rel\":\"preconnect dns-prefetch\",\"href\":\"https://securepubads.g.doubleclick.net\"}],[\"$\",\"link\",null,{\"rel\":\"preconnect dns-prefetch\",\"href\":\"https://cdn-eu.pagesense.io\"}],[\"$\",\"link\",null,{\"rel\":\"preconnect dns-prefetch\",\"href\":\"https://popup.wisepops.com\"}],[\"$\",\"link\",null,{\"rel\":\"preconnect dns-prefetch\",\"href\":\"https://www.medtargetsystem.com\"}],[\"$\",\"$L10\",null,{\"src\":\"https://securepubads.g.doubleclick.net/tag/js/gpt.js\",\"strategy\":\"afterInteractive\"}],[\"$\",\"link\",null,{\"rel\":\"preload\",\"href\":\"https://cookie-cdn.cookiepro.com/scripttemplates/otSDKStub.js\",\"as\":\"script\"}],[\"$\",\"$L10\",null,{\"async\":true,\"src\":\"https://cookie-cdn.cookiepro.com/scripttemplates/otSDKStub.js\",\"type\":\"text/javascript\",\"data-domain-script\":\"565e50dd-f6e9-46d6-91cd-5c40a270264f\",\"id\":\"cookie-pro-script\"}],[\"$\",\"$L10\",null,{\"id\":\"otb-ads-consent\",\"children\":\"function OnetrustAdsConsent() {\\n if (window.googletag \u0026\u0026 window.googletag.apiReady) {\\n googletag.pubads().disableInitialLoad();\\n googletag.pubads().setPrivacySettings({nonPersonalizedAds:!!OptanonActiveGroups.match(/,4,/)});\\n googletag.pubads().refresh();\\n } else {\\n setTimeout(OnetrustAdsConsent, 1000);\\n }\\n}\\nfunction OptanonWrapper() {\\n OnetrustAdsConsent();\\n}\"}]]}],[\"$\",\"body\",null,{\"children\":[[\"$\",\"$L11\",null,{\"adsLazyLoad\":true,\"adSlotIds\":{\"DEFAULT_BOTTOM_AD_ID\":\"/21798771943/SVN-BOTTOM\",\"DEFAULT_TOP_AD_ID\":\"/21798771943/SVN-TOP\",\"DEFAULT_MIDDLE_AD_ID\":\"/21798771943/SVN-MPU\",\"HOMEPAGE_BOTTOM_AD_ID\":\"/21798771943/SVN-HOME-BOTTOM\",\"HOMEPAGE_TOP_AD_ID\":\"/21798771943/SVN-HOME-TOP\"}}],[\"$\",\"$L12\",null,{\"id\":\"gtm-script\",\"children\":\"(function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':\\n new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],\\n j=d.createElement(s),dl=l!='dataLayer'?'\u0026l='+l:'';j.async=true;j.src=\\n 'https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);\\n })(window,document,'script','dataLayer', 'GTM-5SHSDJ');\"}],null,[\"$\",\"div\",null,{\"children\":[\"$undefined\",[\"$\",\"div\",null,{\"className\":\"border-b-bmj-silver-100 bg-bmj-siver-30 border-b flex items-center justify-center py-3 min-w-[auto] min-h-[100px] md:min-h-[250px]\",\"children\":[\"$\",\"div\",null,{\"id\":\"div-gpt-ad-3321227-1\",\"data-testid\":\"top-ad-slot\",\"className\":\"flex items-center justify-center w-[auto] h-[100px] md:h-[250px]\",\"children\":[\"$\",\"$L12\",null,{\"id\":\"slot-ad-div-gpt-ad-3321227-1\",\"children\":\"var googletag=googletag||{cmd:[]};googletag.cmd.push(function() {googletag.display(\\\"div-gpt-ad-3321227-1\\\");});\"}]}]}],[\"$\",\"header\",null,{\"className\":\"hidden flex-wrap items-center justify-between px-4 md:flex md:flex-nowrap\",\"data-testid\":\"header-panel\",\"children\":[[\"$\",\"a\",null,{\"href\":\"https://journals.bmj.com\",\"className\":\"py-2 px-0 flex items-center\",\"children\":[\"$\",\"img\",null,{\"className\":\"h-[42px] w-[154px]\",\"data-testid\":\"bmj-journals-logo\",\"src\":\"/_next/static/media/logo-bmj-journals.c2a2899be06382c530c7bc1e5d61e633.svg\",\"alt\":\"BMJ Journals logo\"}]}],[\"$\",\"nav\",null,{\"className\":\"flex flex-wrap items-center justify-between md:flex-nowrap\",\"children\":[[],[\"$\",\"div\",null,{\"data-testid\":\"search-box\",\"className\":\"flex w-72 flex-col bg-white/20 p-2 pr-4 md:w-[343px] md:flex-row md:items-start md:p-0 md:pr-0 undefined\",\"children\":[[\"$\",\"form\",null,{\"role\":\"search\",\"method\":\"post\",\"action\":\"/search\",\"className\":\"flex undefined\",\"children\":[[\"$\",\"input\",null,{\"type\":\"textbox\",\"placeholder\":\"search\",\"name\":\"keywords\",\"title\":\"Search for:\",\"className\":\"border-bmj-silver-100 rounded-0 h-[34px] w-[207px] appearance-none border p-[5px] pl-[10px] align-middle text-[14px] undefined\"}],[\"$\",\"button\",null,{\"type\":\"submit\",\"name\":\"op\",\"className\":\"bg-bmj-siver-30 border-bmj-silver-100 rounded-0 ml-[-4px] h-[34px] appearance-none border py-[1px] pl-[10px] pr-[12px] text-[13.33px] undefined\",\"children\":\"Search\"}],[\"$\",\"input\",null,{\"type\":\"hidden\",\"name\":\"form_id\",\"value\":\"highwire_search_quicksearch_form_1\"}]]}],[\"$\",\"div\",null,{\"className\":\"flex justify-start pl-[5px] pt-[3px] text-left md:justify-end undefined\",\"children\":[\"$\",\"a\",null,{\"href\":\"/search\",\"title\":\"Advanced Search\",\"className\":\"decoration-none lg:text-bmj-blue-500 mt-2 flex flex-row text-[12.75px] leading-[normal] md:mt-0 md:flex-col [\u0026\u003e:first-of-type]:mr-1 undefined\",\"children\":[[\"$\",\"span\",null,{\"children\":\"Advanced\"}],[\"$\",\"span\",null,{\"children\":\"search\"}]]}]}]]}]]}]]}],[\"$\",\"$L13\",null,{\"hasSidepanelButtons\":false,\"menuData\":{\"navData\":[{\"key\":354,\"displayName\":\"Latest content\",\"link\":\"/content/early/recent\"},{\"key\":355,\"displayName\":\"Current issue\",\"link\":\"/content/current\"},{\"key\":356,\"displayName\":\"Archive\",\"link\":\"/content/by/year\"},{\"key\":357,\"displayName\":\"For authors\",\"link\":\"/pages/authors/\"},{\"key\":358,\"displayName\":\"About\",\"link\":\"/pages/about/\"}]},\"logo\":\"/next-resources/logo.svg\",\"searchFormUrl\":\"/search\",\"headerMenuData\":\"$undefined\",\"children\":[\"$\",\"div\",null,{\"children\":[\"$\",\"$L7\",null,{\"parallelRouterKey\":\"children\",\"segmentPath\":[\"children\"],\"error\":\"$14\",\"errorStyles\":[],\"errorScripts\":[],\"template\":[\"$\",\"$Lb\",null,{}],\"templateStyles\":\"$undefined\",\"templateScripts\":\"$undefined\",\"notFound\":\"$L15\",\"notFoundStyles\":[],\"styles\":null}]}]}],[\"$\",\"footer\",null,{\"children\":[[\"$\",\"div\",null,{\"className\":\"border-bmj-silver-100 border-t-solid m-0 ml-auto mr-auto flex w-full min-w-0 flex-wrap gap-4 border border-b-0 border-l-0 border-r-0 pl-4 pr-4\",\"children\":[[\"$\",\"a\",null,{\"className\":\"my-4\",\"href\":\"http://www.chinastroke.net/\",\"data-testid\":\"association-logo-1-link\",\"aria-label\":\"Chinese Stroke Association\",\"children\":[\"$\",\"$L16\",null,{\"data-testid\":\"association-logo-1\",\"title\":\"Chinese Stroke Association\",\"src\":\"https://svn.bmj.com/svn/wp-content/uploads/sites/57/2023/04/society-logo-csa.png\",\"alt\":\"Chinese Stroke Association\",\"width\":93,\"height\":90}]}]]}],[\"$\",\"div\",null,{\"className\":\"bg-bmj-primary-brand text-bmj-white m-0 mx-auto flex w-full min-w-0 flex-col px-4 md:flex-row\",\"children\":[[\"$\",\"div\",\"360\",{\"data-testid\":\"footer-content\",\"className\":\"md:border-b-none [\u0026:last-child]:border-b-none m-0 ml-auto mr-auto w-full min-w-0 border-b-[1px] border-b-white/50 pr-6 pt-5 pb-4 md:pt-8 md:pb-8\",\"children\":[[\"$\",\"span\",null,{\"className\":\"mt-0 mb-5 block text-base font-normal uppercase leading-4\",\"children\":\"CONTENT\"}],[\"$\",\"ul\",null,{\"className\":\"ml-0 mb-4 pl-0\",\"children\":[[\"$\",\"li\",\"361\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/content/early/recent\",\"children\":\"Latest content\"}]}],[\"$\",\"li\",\"362\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/content/current\",\"children\":\"Current issue\"}]}],[\"$\",\"li\",\"363\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/pages/top-cited-articles/\",\"children\":\"Top cited articles\"}]}],[\"$\",\"li\",\"364\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/pages/most-read-articles/\",\"children\":\"Most Read Articles\"}]}],[\"$\",\"li\",\"365\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/content/by/year\",\"children\":\"Archive\"}]}],[\"$\",\"li\",\"366\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/pages/browse-by-collection/\",\"children\":\"Browse by collection\"}]}],[\"$\",\"li\",\"367\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/eletters\",\"children\":\"Responses\"}]}]]}],[\"$\",\"div\",null,{\"className\":\"flex\",\"children\":[[\"$\",\"a\",\"rss\",{\"href\":\"/pages/rss-feeds\",\"data-testid\":\"rss\",\"className\":\"[\u0026\u003eimg]:m-[2px] [\u0026\u003eimg]:p-[4px] [\u0026\u003eimg]:hover:bg-white/20\",\"children\":[\"$\",\"img\",null,{\"src\":\"https://resources.bmj.com/repository/journals-network-project/images/social-media/rss.svg\",\"alt\":\"rss-icon\",\"width\":\"35\",\"height\":\"35\"}]}],[\"$\",\"a\",\"x\",{\"href\":\"https://twitter.com/SVN_BMJ\",\"data-testid\":\"x\",\"className\":\"[\u0026\u003eimg]:m-[2px] [\u0026\u003eimg]:p-[4px] [\u0026\u003eimg]:hover:bg-white/20\",\"children\":[\"$\",\"img\",null,{\"src\":\"https://resources.bmj.com/repository/journals-network-project/images/social-media/x.svg\",\"alt\":\"x-icon\",\"width\":\"35\",\"height\":\"35\"}]}]]}]]}],[\"$\",\"div\",\"368\",{\"data-testid\":\"footer-journal\",\"className\":\"md:border-b-none [\u0026:last-child]:border-b-none m-0 ml-auto mr-auto w-full min-w-0 border-b-[1px] border-b-white/50 pr-6 pt-5 pb-4 md:pt-8 md:pb-8\",\"children\":[[\"$\",\"span\",null,{\"className\":\"mt-0 mb-5 block text-base font-normal uppercase leading-4\",\"children\":\"JOURNAL\"}],[\"$\",\"ul\",null,{\"className\":\"ml-0 mb-4 pl-0\",\"children\":[[\"$\",\"li\",\"369\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/pages/about/\",\"children\":\"About\"}]}],[\"$\",\"li\",\"370\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/pages/editorial-board/\",\"children\":\"Editorial board\"}]}],[\"$\",\"li\",\"371\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/pages/thank-you-to-our-reviewers/\",\"children\":\"Thank you to our reviewers\"}]}],[\"$\",\"li\",\"372\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"https://myaccount.bmj.com/myaccount/signup.html?regService=etoc-alerts\u0026corpusCode=svnbmj\u0026fwdUrl=https://svn.bmj.com\",\"children\":\"Sign up for email alerts\"}]}]]}],[\"$\",\"div\",null,{\"className\":\"flex\",\"children\":\"$undefined\"}]]}],[\"$\",\"div\",\"244\",{\"data-testid\":\"footer-authors\",\"className\":\"md:border-b-none [\u0026:last-child]:border-b-none m-0 ml-auto mr-auto w-full min-w-0 border-b-[1px] border-b-white/50 pr-6 pt-5 pb-4 md:pt-8 md:pb-8\",\"children\":[[\"$\",\"span\",null,{\"className\":\"mt-0 mb-5 block text-base font-normal uppercase leading-4\",\"children\":\"AUTHORS\"}],[\"$\",\"ul\",null,{\"className\":\"ml-0 mb-4 pl-0\",\"children\":[[\"$\",\"li\",\"245\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/pages/authors/\",\"children\":\"Instructions for authors\"}]}],[\"$\",\"li\",\"251\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"https://mc.manuscriptcentral.com/svn\",\"children\":\"Submit an article\"}]}],[\"$\",\"li\",\"252\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"https://authors.bmj.com/policies/\",\"children\":\"Editorial policies\"}]}],[\"$\",\"li\",\"253\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/pages/faqs/\",\"children\":\"FAQs\"}]}],[\"$\",\"li\",\"254\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"https://openaccess.bmj.com/\",\"children\":\"Open access at BMJ\"}]}],[\"$\",\"li\",\"255\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"https://authors.bmj.com/\",\"children\":\"BMJ Author Hub\"}]}]]}],[\"$\",\"div\",null,{\"className\":\"flex\",\"children\":\"$undefined\"}]]}],[\"$\",\"div\",\"321\",{\"data-testid\":\"footer-help\",\"className\":\"md:border-b-none [\u0026:last-child]:border-b-none m-0 ml-auto mr-auto w-full min-w-0 border-b-[1px] border-b-white/50 pr-6 pt-5 pb-4 md:pt-8 md:pb-8\",\"children\":[[\"$\",\"span\",null,{\"className\":\"mt-0 mb-5 block text-base font-normal uppercase leading-4\",\"children\":\"HELP\"}],[\"$\",\"ul\",null,{\"className\":\"ml-0 mb-4 pl-0\",\"children\":[[\"$\",\"li\",\"322\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"/pages/contact-us/\",\"children\":\"Contact us\"}]}],[\"$\",\"li\",\"323\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"https://journals.bmj.com/cgi/reprintform\",\"children\":\"Reprints\"}]}],[\"$\",\"li\",\"324\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"https://www.bmj.com/company/products-services/rights-and-licensing/permissions\",\"children\":\"Permissions\"}]}],[\"$\",\"li\",\"325\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"https://www.bmj.com/company/for-advertisers-and-sponsor/\",\"children\":\"Advertising\"}]}],[\"$\",\"li\",\"326\",{\"className\":\"mb-4 list-none leading-none [\u0026:last-child]:mb-0\",\"children\":[\"$\",\"a\",null,{\"className\":\"text-bmj-white leading-none no-underline [\u0026:hover]:underline\",\"href\":\"https://myaccount.bmj.com/myaccount/customerservice/salesforce-form.html\",\"children\":\"Feedback form\"}]}]]}],[\"$\",\"div\",null,{\"className\":\"flex\",\"children\":\"$undefined\"}]]}]]}],[\"$\",\"div\",null,{\"className\":\"justify-normal m-0 mx-auto flex w-full min-w-0 flex-col px-4 pt-4 md:flex-row md:justify-between\",\"children\":[[\"$\",\"div\",null,{\"className\":\"relative h-[35px] w-[60px]\",\"children\":[\"$\",\"a\",null,{\"data-testid\":\"bmj-footer-logo-link\",\"href\":\"https://www.bmj.com/company/\",\"children\":[\"$\",\"img\",null,{\"src\":\"/_next/static/media/bmj-footer-logo.c6e1ad28003cb22dbd978555514ed05c.svg\",\"alt\":\"bmj-footer-logo\",\"height\":\"35\"}]}]}],[\"$\",\"div\",null,{\"data-testid\":\"copyright-data-wrapper\",\"className\":\"flex flex-col items-start md:items-end [\u0026\u003e:first-of-type]:mt-0 [\u0026\u003espan:nth-of-type(2)]:whitespace-normal\",\"children\":[[\"$\",\"a\",\"website-terms-and-conditions\",{\"data-testid\":\"website-terms-and-conditions\",\"href\":\"https://www.bmj.com/company/legal-information/\",\"className\":\"decoration-none text-bmj-normal text-bmj-blue-500 [\u0026:hover]:decoration-none [\u0026:hover]:text-bmj-primary-brand mb-2 [\u0026\u0026\u0026]:mt-2 [\u0026\u0026\u0026]:md:mt-0\",\"children\":\"Website Terms \u0026 Conditions\"}],[\"$\",\"a\",\"privacy-and-cookies\",{\"data-testid\":\"privacy-and-cookies\",\"href\":\"https://www.bmj.com/company/your-privacy/\",\"className\":\"decoration-none text-bmj-normal text-bmj-blue-500 [\u0026:hover]:decoration-none [\u0026:hover]:text-bmj-primary-brand mb-2 [\u0026\u0026\u0026]:mt-2 [\u0026\u0026\u0026]:md:mt-0\",\"children\":\"Privacy \u0026 Cookies\"}],[\"$\",\"a\",\"contact-bmj\",{\"data-testid\":\"contact-bmj\",\"href\":\"https://www.bmj.com/company/contact-us/\",\"className\":\"decoration-none text-bmj-normal text-bmj-blue-500 [\u0026:hover]:decoration-none [\u0026:hover]:text-bmj-primary-brand mb-2 [\u0026\u0026\u0026]:mt-2 [\u0026\u0026\u0026]:md:mt-0\",\"children\":\"Contact BMJ\"}],[\"$\",\"a\",null,{\"href\":\"#!\",\"data-testid\":\"cookie-settings\",\"id\":\"ot-sdk-btn\",\"className\":\"ot-sdk-show-settings decoration-none !mt:0 mb-2 cursor-pointer !border !border-[#43791A] !bg-transparent px-2 py-1 !text-[0.875rem] !text-[#43791A] duration-100 ease-linear md:mb-0 [\u0026:hover]:!bg-[#43791A] [\u0026:hover]:!text-white\",\"children\":\"Cookie settings\"}],[\"$\",\"span\",\"online-issn\",{\"data-testid\":\"online-issn\",\"className\":\"text-bmj-silver-800 whitespace-pre text-sm leading-normal [\u0026\u0026\u0026]:mt-2\",\"children\":\"Online ISSN: 2059-8696\"}],[\"$\",\"span\",\"copyright\",{\"data-testid\":\"copyright\",\"className\":\"text-bmj-silver-800 mb-2 mt-2 whitespace-pre text-[0.875rem]\",\"children\":\"Copyright © 2024 Chinese Stroke Association. All rights reserved.\"}]]}]]}]]}],[\"$\",\"div\",null,{\"className\":\"border-t-divider bg-bmj-siver-30 border-t flex items-center justify-center py-3 min-w-[auto] min-h-[100px] md:min-h-[250px]\",\"children\":[\"$\",\"div\",null,{\"id\":\"div-gpt-ad-3321227-2\",\"data-testid\":\"bottom-ad-slot\",\"className\":\"flex items-center justify-center w-[auto] h-[100px] md:h-[250px]\",\"children\":[\"$\",\"$L12\",null,{\"id\":\"slot-ad-div-gpt-ad-3321227-2\",\"children\":\"var googletag=googletag||{cmd:[]};googletag.cmd.push(function() {googletag.display(\\\"div-gpt-ad-3321227-2\\\");});\"}]}]}]]}]]}]]}]\n"])</script><script>self.__next_f.push([1,"15:[[\"$\",\"div\",null,{\"className\":\"flex justify-between bg-white pt-2 md:mb-10 mb-[24px]\",\"children\":[[\"$\",\"div\",null,{\"children\":[\"$\",\"div\",null,{\"data-testid\":\"breadcrumbs\",\"className\":\"px-4\",\"children\":[]}]}],[\"$\",\"a\",null,{\"href\":\"https://myaccount.bmj.com/myaccount/signup.html?regService=etoc-alerts\u0026corpusCode=svnbmj\u0026fwdUrl=https://svn.bmj.com\",\"className\":\"undefined text-bmj-blue-600 [\u0026:hover]:text-bmj-blue-700 hidden no-underline md:inline-block\",\"children\":[\"$\",\"div\",null,{\"className\":\"flex\",\"children\":[[\"$\",\"div\",null,{\"className\":\"mr-2 flex\",\"children\":[\"$\",\"svg\",null,{\"className\":\"text-bmj-primary-brand h-4 w-8\",\"data-testid\":\"envelope-icon\",\"viewBox\":\"0 0 33 22\",\"fill\":\"none\",\"xmlns\":\"http://www.w3.org/2000/svg\",\"children\":[[\"$\",\"path\",null,{\"d\":\"M1 1H32V21H1V1Z\",\"fill\":\"white\",\"stroke\":\"currentColor\"}],[\"$\",\"path\",null,{\"d\":\"M31.9 20.8L21 9\",\"stroke\":\"currentColor\"}],[\"$\",\"path\",null,{\"d\":\"M1 20.5L11.8 9\",\"stroke\":\"currentColor\"}],[\"$\",\"mask\",null,{\"id\":\"path-4-inside-1\",\"fill\":\"white\",\"children\":[\"$\",\"path\",null,{\"d\":\"M0.600098 0.700012L16.6001 13.4L32.4001 0.900012\"}]}],[\"$\",\"path\",null,{\"d\":\"M16.6001 13.4L15.9784 14.1833L16.5991 14.6759L17.2205 14.1843L16.6001 13.4ZM-0.0216079 1.48326L15.9784 14.1833L17.2218 12.6168L1.2218 -0.0832389L-0.0216079 1.48326ZM17.2205 14.1843L33.0205 1.68426L31.7797 0.115765L15.9796 12.6158L17.2205 14.1843Z\",\"fill\":\"currentColor\",\"mask\":\"url(#path-4-inside-1)\"}]]}]}],[\"$\",\"span\",null,{\"className\":\"mr-4 text-base leading-4\",\"data-testid\":\"email-alerts-link\",\"children\":\"Email alerts\"}]]}]}]]}],[\"$\",\"div\",null,{\"data-testid\":\"404-page\",\"className\":\"flex min-h-[30rem] flex-col items-center justify-center pb-12 md:flex-row\",\"children\":[[\"$\",\"img\",null,{\"src\":\"https://thebmj-frontend.bmj.com/next-resources/404-missing.svg\",\"width\":\"143\",\"height\":\"134\",\"alt\":\"not found\"}],[\"$\",\"div\",null,{\"data-testid\":\"page-contain-link\",\"className\":\"flex w-full flex-col px-8 md:w-[50%] lg:px-16\",\"children\":[[\"$\",\"p\",null,{\"className\":\"py-4\",\"children\":\"Error 404: Not found\"}],[\"$\",\"p\",null,{\"className\":\"wrap-urls m-0 mt-3 text-[1.625rem] font-bold leading-9\",\"children\":\"Sorry, the page you requested is unavailable.\"}],[\"$\",\"p\",null,{\"className\":\"text-4 mb-4 mt-1 leading-6\",\"children\":[\"The link might be broken or no longer exist. If you believe this is an error, please\",\" \",[\"$\",\"a\",null,{\"href\":\"https://myaccount.bmj.com/myaccount/customerservice/support-home.html\",\"className\":\"decoration-none text-bmj-site-links [\u0026:hover]:decoration-underline\",\"children\":\"contact us.\"}]]}],[\"$\",\"p\",null,{\"className\":\"m-0 mt-3 mb-4 text-[1.625rem] font-bold leading-9\",\"children\":\"Other useful links\"}],[[\"$\",\"ul\",\"/\",{\"data-testid\":\"link-number-0\",\"className\":\"m-0 mt-2 list-none p-0 first-of-type:mt-0\",\"children\":[\"$\",\"li\",null,{\"children\":[\"$\",\"a\",null,{\"href\":\"/\",\"className\":\"decoration-none text-bmj-site-links [\u0026:hover]:decoration-underline\",\"children\":\"Homepage\"}]}]}],[\"$\",\"ul\",\"/content/current\",{\"data-testid\":\"link-number-1\",\"className\":\"m-0 mt-2 list-none p-0 first-of-type:mt-0\",\"children\":[\"$\",\"li\",null,{\"children\":[\"$\",\"a\",null,{\"href\":\"/content/current\",\"className\":\"decoration-none text-bmj-site-links [\u0026:hover]:decoration-underline\",\"children\":\"Current issue\"}]}]}],[\"$\",\"ul\",\"/pages/authors\",{\"data-testid\":\"link-number-2\",\"className\":\"m-0 mt-2 list-none p-0 first-of-type:mt-0\",\"children\":[\"$\",\"li\",null,{\"children\":[\"$\",\"a\",null,{\"href\":\"/pages/authors\",\"className\":\"decoration-none text-bmj-site-links [\u0026:hover]:decoration-underline\",\"children\":\"Authors\"}]}]}],[\"$\",\"ul\",\"/pages/about\",{\"data-testid\":\"link-number-3\",\"className\":\"m-0 mt-2 list-none p-0 first-of-type:mt-0\",\"children\":[\"$\",\"li\",null,{\"children\":[\"$\",\"a\",null,{\"href\":\"/pages/about\",\"className\":\"decoration-none text-bmj-site-links [\u0026:hover]:decoration-underline\",\"children\":\"About\"}]}]}],[\"$\",\"ul\",\"/pages/contact-us\",{\"data-testid\":\"link-number-4\",\"className\":\"m-0 mt-2 list-none p-0 first-of-type:mt-0\",\"children\":[\"$\",\"li\",null,{\"children\":[\"$\",\"a\",null,{\"href\":\"/pages/contact-us\",\"className\":\"decoration-none text-bmj-site-links [\u0026:hover]:decoration-underline\",\"children\":\"Help\"}]}]}],[\"$\",\"ul\",\"https://www.bmj.com/company/products-services/rights-and-licensing/permissions/\",{\"data-testid\":\"link-number-5\",\"className\":\"m-0 mt-2 list-none p-0 first-of-type:mt-0\",\"children\":[\"$\",\"li\",null,{\"children\":[\"$\",\"a\",null,{\"href\":\"https://www.bmj.com/company/products-services/rights-and-licensing/permissions/\",\"className\":\"decoration-none text-bmj-site-links [\u0026:hover]:decoration-underline\",\"children\":\"Permissions\"}]}]}]]]}]]}]]\n"])</script><script>self.__next_f.push([1,"1c:I[5220,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"NavigationProvider\"]\n1d:I[6772,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"FloatingBar\"]\n1e:\"$Sreact.fragment\"\n1f:I[5901,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"TitleSection\"]\n23:I[1053,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"AuthorsList\"]\n25:I[7925,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-"])</script><script>self.__next_f.push([1,"297afc00ae9fdb76.js\"],\"default\"]\n26:I[5426,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"BackToTop\"]\n29:I[5828,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"LoadFigures\"]\n2b:I[3667,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"default\"]\n2d:I[6021,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5BarticleId%5D/page-297afc00ae9fdb76.js\"],\"AddContributorSvgComponent\"]\n2e:I[1715,[\"611\",\"static/chunks/9af238c7-693cab6698f4b9fe.js\",\"431\",\"static/chunks/22747d63-441d638379b6d561.js\",\"352\",\"static/chunks/352-9002e424cdc49415.js\",\"789\",\"static/chunks/789-d2923bae8cb39657.js\",\"809\",\"static/chunks/809-5ff6e64efd158e65.js\",\"21\",\"static/chunks/21-54856eee41e993bd.js\",\"581\",\"static/chunks/app/content/%5Bvolume%5D/%5Bissue%5D/%5Barticl"])</script><script>self.__next_f.push([1,"eId%5D/page-297afc00ae9fdb76.js\"],\"RapidResponses\"]\n17:T7ba,Background Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.Methods Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.Results These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p\u003c0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p\u003c0.05) and caused acute instead of prolonged impairment of spatial reference memory (p\u003c0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p\u003c0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p\u003e0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p\u003c0.05).Conclusion We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI.18:T7ba,Ba"])</script><script>self.__next_f.push([1,"ckground Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.Methods Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.Results These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p\u003c0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p\u003c0.05) and caused acute instead of prolonged impairment of spatial reference memory (p\u003c0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p\u003c0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p\u003e0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p\u003c0.05).Conclusion We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI.19:T7ba,Background Vascular cognitive impairment (VCI) is the second-lea"])</script><script>self.__next_f.push([1,"ding cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.Methods Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.Results These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p\u003c0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p\u003c0.05) and caused acute instead of prolonged impairment of spatial reference memory (p\u003c0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p\u003c0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p\u003e0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p\u003c0.05).Conclusion We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI.1a:T7ba,Background Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrova"])</script><script>self.__next_f.push([1,"scular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.Methods Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.Results These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p\u003c0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p\u003c0.05) and caused acute instead of prolonged impairment of spatial reference memory (p\u003c0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p\u003c0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p\u003e0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p\u003c0.05).Conclusion We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI.1b:T7ba,Background Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are n"])</script><script>self.__next_f.push([1,"o appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.Methods Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.Results These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p\u003c0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p\u003c0.05) and caused acute instead of prolonged impairment of spatial reference memory (p\u003c0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p\u003c0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p\u003e0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p\u003c0.05).Conclusion We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI."])</script><script>self.__next_f.push([1,"d:[[\"$\",\"meta\",\"0\",{\"name\":\"viewport\",\"content\":\"width=device-width, initial-scale=1\"}],[\"$\",\"meta\",\"1\",{\"charSet\":\"utf-8\"}],[\"$\",\"title\",\"2\",{\"children\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice | Stroke and Vascular Neurology\"}],[\"$\",\"meta\",\"3\",{\"name\":\"description\",\"content\":\"$17\"}],[\"$\",\"meta\",\"4\",{\"name\":\"DC.Contributor\",\"content\":\"Zhiyuan Zhou\"}],[\"$\",\"meta\",\"5\",{\"name\":\"DC.Contributor\",\"content\":\"Yuanyuan Ma\"}],[\"$\",\"meta\",\"6\",{\"name\":\"DC.Contributor\",\"content\":\"Tongtong Xu\"}],[\"$\",\"meta\",\"7\",{\"name\":\"DC.Contributor\",\"content\":\"Shengju Wu\"}],[\"$\",\"meta\",\"8\",{\"name\":\"DC.Contributor\",\"content\":\"Guo-Yuan Yang\"}],[\"$\",\"meta\",\"9\",{\"name\":\"DC.Contributor\",\"content\":\"Jing Ding\"}],[\"$\",\"meta\",\"10\",{\"name\":\"DC.Contributor\",\"content\":\"Xin Wang\"}],[\"$\",\"meta\",\"11\",{\"name\":\"DC.Format\",\"content\":\"text/html\"}],[\"$\",\"meta\",\"12\",{\"name\":\"DC.Identifier\",\"content\":\"10.1136/svn-2022-001594\"}],[\"$\",\"meta\",\"13\",{\"name\":\"DC.Language\",\"content\":\"en\"}],[\"$\",\"meta\",\"14\",{\"name\":\"DC.Publisher\",\"content\":\"BMJ Publishing Group Ltd\"}],[\"$\",\"meta\",\"15\",{\"name\":\"DC.AccessRights\",\"content\":\"open-access\"}],[\"$\",\"meta\",\"16\",{\"name\":\"DC.Title\",\"content\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\"}],[\"$\",\"meta\",\"17\",{\"name\":\"DC.Description\",\"content\":\"$18\"}],[\"$\",\"meta\",\"18\",{\"name\":\"DC.Date\",\"content\":\"2022-12-20\"}],[\"$\",\"meta\",\"19\",{\"name\":\"DC.Type\",\"content\":\"journal-article\"}],[\"$\",\"meta\",\"20\",{\"name\":\"DC.Rights\",\"content\":\"This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license\"}],[\"$\",\"meta\",\"21\",{\"name\":\"citation_title\",\"content\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\"}],[\"$\",\"meta\",\"22\",{\"name\":\"citation_abstract\",\"content\":\"$19\"}],[\"$\",\"meta\",\"23\",{\"name\":\"citation_journal_title\",\"content\":\"Stroke and Vascular Neurology\"}],[\"$\",\"meta\",\"24\",{\"name\":\"citation_publisher\",\"content\":\"BMJ Publishing Group Ltd\"}],[\"$\",\"meta\",\"25\",{\"name\":\"citation_publication_date\",\"content\":\"2022-12-20\"}],[\"$\",\"meta\",\"26\",{\"name\":\"citation_volume\",\"content\":\"7\"}],[\"$\",\"meta\",\"27\",{\"name\":\"citation_issue\",\"content\":\"6\"}],[\"$\",\"meta\",\"28\",{\"name\":\"citation_doi\",\"content\":\"10.1136/svn-2022-001594\"}],[\"$\",\"meta\",\"29\",{\"name\":\"citation_mjid\",\"content\":\"svnbmj;7/6/null\"}],[\"$\",\"meta\",\"30\",{\"name\":\"citation_id\",\"content\":\"7/6/null\"}],[\"$\",\"meta\",\"31\",{\"name\":\"citation_public_url\",\"content\":\"https://svn.bmj.com/content/7/6/527\"}],[\"$\",\"meta\",\"32\",{\"name\":\"citation_full_html_url\",\"content\":\"https://svn.bmj.com/content/7/6/527\"}],[\"$\",\"meta\",\"33\",{\"name\":\"citation_pdf_url\",\"content\":\"https://svn.bmj.com/content/7/6/527.full.pdf\"}],[\"$\",\"meta\",\"34\",{\"name\":\"citation_issn\",\"content\":\"2059-8696\"}],[\"$\",\"meta\",\"35\",{\"name\":\"citation_journal_abbrev\",\"content\":\"Stroke Vasc Neurol\"}],[\"$\",\"meta\",\"36\",{\"name\":\"citation_pmid\",\"content\":\"10.1136/svn-2022-001594\"}],[\"$\",\"meta\",\"37\",{\"name\":\"citation_article_type\",\"content\":\"research-article\"}],[\"$\",\"meta\",\"38\",{\"name\":\"citation_section\",\"content\":\"Original research\"}],[\"$\",\"meta\",\"39\",{\"name\":\"citation_access\",\"content\":\"open-access\"}],[\"$\",\"link\",\"40\",{\"rel\":\"canonical\",\"href\":\"https://svn.bmj.com/content/7/6/527\"}],[\"$\",\"link\",\"41\",{\"rel\":\"alternate\",\"type\":\"application/pdf\",\"href\":\"https://svn.bmj.com/content/7/6/527.full.pdf\"}],[\"$\",\"meta\",\"42\",{\"property\":\"og:title\",\"content\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\"}],[\"$\",\"meta\",\"43\",{\"property\":\"og:description\",\"content\":\"$1a\"}],[\"$\",\"meta\",\"44\",{\"property\":\"og:url\",\"content\":\"https://svn.bmj.com/content/7/6/527\"}],[\"$\",\"meta\",\"45\",{\"property\":\"og:site_name\",\"content\":\"Stroke and Vascular Neurology\"}],[\"$\",\"meta\",\"46\",{\"property\":\"og:locale\",\"content\":\"en_GB\"}],[\"$\",\"meta\",\"47\",{\"property\":\"og:image\",\"content\":\"https://svn.bmj.com/content/svnbmj/7/6/527/F1.medium.gif\"}],[\"$\",\"meta\",\"48\",{\"property\":\"og:image:width\",\"content\":\"800\"}],[\"$\",\"meta\",\"49\",{\"property\":\"og:image:height\",\"content\":\"600\"}],[\"$\",\"meta\",\"50\",{\"property\":\"og:image:alt\",\"content\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\"}],[\"$\",\"meta\",\"51\",{\"property\":\"og:image\",\"content\":\"https://svn.bmj.com/content/svnbmj/7/6/527/F1.large.jpg\"}],[\"$\",\"meta\",\"52\",{\"property\":\"og:image:width\",\"content\":\"1800\"}],[\"$\",\"meta\",\"53\",{\"property\":\"og:image:height\",\"content\":\"1600\"}],[\"$\",\"meta\",\"54\",{\"property\":\"og:image:alt\",\"content\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\"}],[\"$\",\"meta\",\"55\",{\"property\":\"og:type\",\"content\":\"website\"}],[\"$\",\"meta\",\"56\",{\"name\":\"twitter:card\",\"content\":\"summary_large_image\"}],[\"$\",\"meta\",\"57\",{\"name\":\"twitter:site\",\"content\":\"@bmj_latest\"}],[\"$\",\"meta\",\"58\",{\"name\":\"twitter:title\",\"content\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\"}],[\"$\",\"meta\",\"59\",{\"name\":\"twitter:description\",\"content\":\"$1b\"}],[\"$\",\"meta\",\"60\",{\"name\":\"twitter:image\",\"content\":\"https://svn.bmj.com/content/svnbmj/7/6/527/F1.medium.gif\"}],[\"$\",\"meta\",\"61\",{\"name\":\"twitter:image:alt\",\"content\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\"}]]\n"])</script><script>self.__next_f.push([1,"5:null\n20:{\"id\":\"svnbmj\",\"title\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\",\"licenseUrl\":\"http://creativecommons.org/licenses/by-nc/4.0/\",\"accessType\":\"open-access\",\"isOpenAccess\":\"true\",\"publicationDateTimestamp\":\"2022-12-20\",\"authorList\":\"Zhiyuan Zhou, Yuanyuan Ma, Tongtong Xu, Shengju Wu, Guo-Yuan Yang, Jing Ding, Xin Wang\",\"volume\":\"7\",\"issue\":\"6\",\"firstPage\":\"527\",\"lastPage\":\"533\"}\n21:{\"title\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\",\"authorDisplay\":\"Zhiyuan Zhou, Yuanyuan Ma, Tongtong Xu, Shengju Wu, Guo-Yuan Yang, Jing Ding, Xin Wang\",\"elocationId\":null,\"journalName\":\"Stroke and Vascular Neurology\",\"publicationYear\":\"2022\",\"volume\":\"7\"}\n22:{\"title\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\",\"articleUrl\":\"https://svn.bmj.com/content/7/6/527\"}\n24:[[\"Department of Neurology, Zhongshan Hospital Fudan University, Shanghai, China\",1],[\"Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China\",2],[\" Department of the State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China\",3]]\n27:T492,The BCAS model was established by using microcoils specifically designed for the mouse (microcoil specifications: piano wire diameter: 0.08 mm, total length: 2.5 mm, internal diameters: 0.16 mm and 0.18 mm, Anruike Biotechnology, Xi 'an, China). Animals (n=56) were induced anaesthesia with 5% isoflurane/95% air mixture and maintained to anaesthesia by 5% isoflurane/95% air mixture during operation. The left and right CCA were exposed and isolated from the surrounding sheaths. Then microcoils were twined by rotating it around each CCA. The site of operation was sutured. During the operation, 16 mice failed to survive because of the acute severe CBF reduction. The survived mice were observed and taken care of post-operation unti"])</script><script>self.__next_f.push([1,"l being conscious and recovered to freely access food and water ad libitum. The operated mice were further divided into three subgroups according to different internal diameters of the microcoils: 0.16 mm group (n=7), 0.16/0.18 mm (0.16 mm for the right CCA/0.18 mm for the left CCA) group (n=10) and 0.18 mm group (n=11). Mice in the control group underwent the identical operation without occlusion of CCAs (n=12).28:T588, Mice were subjected to MWM test for spatial learning and memory evaluation. A circular pool (diameter: 20 cm; height: 50 cm) filled with water at 22 °C was divided into four equal quadrants. A video camera was hanging over the pool and four different references were hung on the wall of different directions. A white platform (diameter: 8 cm) was submerged 1 cm below the surface of the water surface. The position of each reference inside and outside the maze was kept unchanged during the training sessions. For the acquisition period, each mouse received one session per day for 5 days (D1–D5) consecutively. Each session consisted of four trials with an interval of 10 min. During each trial, mice were gently placed in the pool towards the wall of the maze at one of the four starting positions. The time mice spending on finding the hidden platform (escape latency) and the swimming track were automatically recorded by the Anymaze software (Stoelting, Naperville, USA). The maximum test time for each per is 60 s. If the mouse failed to locate the target platform within 60 s, then it was guided to the platform and stayed for 15 s. On D6, the platform was removed, mice were subjected to a probe test. The time and distance mice spending in the target quadrant (quadrant concluding the platform) and times that mice crossed the platform area were all recorded by the Anymaze software.2a:T48f, we further explored CBF reduction in BCAS mice induced by 0.16/0.18 mm diameter microcoils (using a 0.16 mm diameter microcoil on one side of the CCA and a 0.18 mm diameter microcoil "])</script><script>self.__next_f.push([1,"on the other). We aimed to clarify whether 0.16/0.18 mm diameter microcoils achieved a balance between the mortality and severity and which diameter microcoil was more appropriate to induce the BCAS model closely mimicking the CBF changes of VCI patients. In addition, we compared the CBF reduction pattern in the BCAS model with the other common VCI mouse models including tBBCAO and rUCCAO. Lastly, the spatial reference memory impairment was investigated among these three VCI mouse models. We demonstrated that the BCAS model was more likely to decipher the haemodynamics changes in VCI patients, and the 0.16/0.18 mm diameter microcoil was more appropriate to induce the BCAS model in mice because of the relative low mortality and lasting CBF reduction. Moreover, the asymmetrical ischaemia of right and left hemispheres in this model was closer to the clinical situation in which patients with carotid plaque usually showed asymmetric stenosis of the carotid artery.2c:T43d,\u003chtml\u003e\u003chead\u003e\u003c/head\u003e\u003cbody\u003e\u003cdiv class=\"section fn-group\" id=\"fn-group-1\"\u003e\u003cul\u003e\u003cli class=\"fn-other\" id=\"fn-1\"\u003e\u003cp id=\"p-40\"\u003eZZ and YM contributed equally.\u003c/p\u003e\u003c/li\u003e\u003cli class=\"fn-other\" id=\"fn-2\"\u003e\u003cp id=\"p-41\"\u003e\u003cspan class=\"fn-label font-bold\"\u003eCorrection notice:\u003c/span\u003e This article has been amended since it was first published. There was a spelling mistake in figure 4 and this now been corrected.\u003c/p\u003e\u003c/li\u003e\u003cli class=\"fn-other\" id=\"fn-3\"\u003e\u003cp id=\"p-42\"\u003e\u003cspan class=\"fn-label font-bold\"\u003eContributors:\u003c/span\u003e ZZ collected data and wrote the manuscript; YM helped revise figures and the manuscript; TX and SW helped do the animal models and also the behavior test; G-YY helped revise the manuscript; JD and XW were responsible for the overall content as the guarantors.\u003c/p\u003e\u003c/li\u003e\u003cli class=\"fn-conflict\" id=\"fn-4\"\u003e\u003cp id=\"p-43\"\u003e\u003cspan class=\"fn-label font-bold\"\u003eCompeting interests:\u003c/span\u003e None declared.\u003c/p\u003e\u003c/li\u003e\u003cli class=\"fn-other\" id=\"fn-5\"\u003e\u003cp id=\"p-44\"\u003e\u003cspan class=\"fn-label font-bold\"\u003eProvenance and peer review:\u003c/span\u003e Not commissioned; externally peer reviewed.\u003c/p\u003e\u003c/li\u003e\u003c/u"])</script><script>self.__next_f.push([1,"l\u003e\u003c/div\u003e\u003c/body\u003e\u003c/html\u003e"])</script><script>self.__next_f.push([1,"6:[[[\"$\",\"meta\",\"author-undefined\",{\"name\":\"citation_author\",\"content\":\"$undefined\"}],[\"$\",\"meta\",\"affiliation-undefined\",{\"name\":\"citation_author_institution\",\"content\":\"$undefined\"}]],[],[\"$\",\"$L1c\",null,{\"children\":[\"$\",\"div\",null,{\"children\":[[\"$\",\"$L1d\",null,{\"title\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\",\"overviewStatements\":[{\"anchorText\":\"Abstract\",\"anchorId\":\"abstract-1\"},{\"anchorText\":\"Introduction\",\"anchorId\":\"sec-8\"},{\"anchorText\":\"Materials and methods\",\"anchorId\":\"sec-9\"},{\"anchorText\":\"Results\",\"anchorId\":\"sec-21\"},{\"anchorText\":\"Discussion\",\"anchorId\":\"sec-28\"},{\"anchorText\":\"References\",\"anchorId\":\"ref-list-1\"},{\"anchorText\":\"Footnotes\",\"anchorId\":\"fn-group-1\"},{\"anchorText\":\"Publication history\",\"anchorId\":\"history-list\"},{\"anchorText\":\"Rapid Responses\",\"anchorId\":\"rapid-responses\"}],\"articleCitationData\":{\"title\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\",\"authorDisplay\":\"Zhiyuan Zhou, Yuanyuan Ma, Tongtong Xu, Shengju Wu, Guo-Yuan Yang, Jing Ding, Xin Wang\",\"elocationId\":null,\"journalName\":\"Stroke and Vascular Neurology\",\"publicationYear\":\"2022\",\"volume\":\"7\"},\"articlePath\":\"7/6/527\",\"doi\":\"10.1136/svn-2022-001594\",\"copyrightStatement\":\"\",\"fullTextPdfPath\":\"/svnbmj/7/6/527.full.pdf\",\"licenceStatement\":\"http://creativecommons.org/licenses/by-nc/4.0/http://creativecommons.org/licenses/by-nc/4.0/\",\"rightsAndPermissionsData\":{\"id\":\"svnbmj\",\"title\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\",\"licenseUrl\":\"http://creativecommons.org/licenses/by-nc/4.0/\",\"accessType\":\"open-access\",\"isOpenAccess\":\"true\",\"publicationDateTimestamp\":\"2022-12-20\",\"authorList\":\"Zhiyuan Zhou, Yuanyuan Ma, Tongtong Xu, Shengju Wu, Guo-Yuan Yang, Jing Ding, Xin Wang\",\"volume\":\"7\",\"issue\":\"6\",\"firstPage\":\"527\",\"lastPage\":\"533\"},\"shareData\":{\"title\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\",\"articleUrl\":\"https://svn.bmj.com/content/7/6/527\"}}],[\"$\",\"div\",null,{\"className\":\"bg-white\",\"children\":[\"$\",\"div\",null,{\"className\":\"flex justify-between bg-white pt-2 md:mb-10 mb-[24px]\",\"children\":[[\"$\",\"div\",null,{\"children\":[\"$\",\"div\",null,{\"data-testid\":\"breadcrumbs\",\"className\":\"px-4\",\"children\":[[\"$\",\"$1e\",\"/\",{\"children\":[[\"$\",\"span\",null,{\"className\":\"text-bmj-font-color-medium text-sm font-normal not-italic leading-4\",\"data-testid\":\"ancestor-wrapper\",\"children\":[\"$\",\"a\",null,{\"className\":\"decoration-none text-bmj-blue-600 hover:text-bmj-blue-700 text-sm font-normal no-underline\",\"data-testid\":\"home\",\"href\":\"/\",\"children\":\"Home\"}]}],[\"$\",\"span\",null,{\"className\":\"text-bmj-grey-breadcrumb m-2 text-sm\",\"children\":\"/\"}]]}],[\"$\",\"$1e\",\"/content/by/year\",{\"children\":[[\"$\",\"span\",null,{\"className\":\"text-bmj-font-color-medium text-sm font-normal not-italic leading-4\",\"data-testid\":\"ancestor-wrapper\",\"children\":[\"$\",\"a\",null,{\"className\":\"decoration-none text-bmj-blue-600 hover:text-bmj-blue-700 text-sm font-normal no-underline\",\"data-testid\":\"archive\",\"href\":\"/content/by/year\",\"children\":\"Archive\"}]}],[\"$\",\"span\",null,{\"className\":\"text-bmj-grey-breadcrumb m-2 text-sm\",\"children\":\"/\"}]]}],[\"$\",\"$1e\",\"/content/7/6\",{\"children\":[[\"$\",\"span\",null,{\"className\":\"text-bmj-font-color-medium text-sm font-normal not-italic leading-4\",\"data-testid\":\"ancestor-wrapper\",\"children\":[\"$\",\"a\",null,{\"className\":\"decoration-none text-bmj-blue-600 hover:text-bmj-blue-700 text-sm font-normal no-underline\",\"data-testid\":\"volume 7, issue 6\",\"href\":\"/content/7/6\",\"children\":\"Volume 7, Issue 6\"}]}],false]}]]}]}],[\"$\",\"a\",null,{\"href\":\"https://myaccount.bmj.com/myaccount/signup.html?regService=etoc-alerts\u0026corpusCode=svnbmj\u0026fwdUrl=https://svn.bmj.com\",\"className\":\"undefined text-bmj-blue-600 [\u0026:hover]:text-bmj-blue-700 hidden no-underline md:inline-block\",\"children\":[\"$\",\"div\",null,{\"className\":\"flex\",\"children\":[[\"$\",\"div\",null,{\"className\":\"mr-2 flex\",\"children\":[\"$\",\"svg\",null,{\"className\":\"text-bmj-primary-brand h-4 w-8\",\"data-testid\":\"envelope-icon\",\"viewBox\":\"0 0 33 22\",\"fill\":\"none\",\"xmlns\":\"http://www.w3.org/2000/svg\",\"children\":[[\"$\",\"path\",null,{\"d\":\"M1 1H32V21H1V1Z\",\"fill\":\"white\",\"stroke\":\"currentColor\"}],[\"$\",\"path\",null,{\"d\":\"M31.9 20.8L21 9\",\"stroke\":\"currentColor\"}],[\"$\",\"path\",null,{\"d\":\"M1 20.5L11.8 9\",\"stroke\":\"currentColor\"}],[\"$\",\"mask\",null,{\"id\":\"path-4-inside-1\",\"fill\":\"white\",\"children\":[\"$\",\"path\",null,{\"d\":\"M0.600098 0.700012L16.6001 13.4L32.4001 0.900012\"}]}],[\"$\",\"path\",null,{\"d\":\"M16.6001 13.4L15.9784 14.1833L16.5991 14.6759L17.2205 14.1843L16.6001 13.4ZM-0.0216079 1.48326L15.9784 14.1833L17.2218 12.6168L1.2218 -0.0832389L-0.0216079 1.48326ZM17.2205 14.1843L33.0205 1.68426L31.7797 0.115765L15.9796 12.6158L17.2205 14.1843Z\",\"fill\":\"currentColor\",\"mask\":\"url(#path-4-inside-1)\"}]]}]}],[\"$\",\"span\",null,{\"className\":\"mr-4 text-base leading-4\",\"data-testid\":\"email-alerts-link\",\"children\":\"Email alerts\"}]]}]}]]}]}],[\"$\",\"div\",null,{\"className\":\"prose mx-auto mb-[24px] w-full max-w-screen-2xl px-4 pb-10 lg:pb-20 xl:w-[85%]\",\"children\":[null,[\"$\",\"$L1f\",null,{\"publicationDate\":\"2022-12-20\",\"articleTypeLabel\":\"Original research\",\"acceptedDate\":\"2022-05-11\",\"receivedDate\":\"2022-04-04\",\"rightsAndPermissionsData\":\"$20\",\"licenceStatement\":\"http://creativecommons.org/licenses/by-nc/4.0/http://creativecommons.org/licenses/by-nc/4.0/\",\"doi\":\"10.1136/svn-2022-001594\",\"articleCitationData\":\"$21\",\"articlePath\":\"7/6/527\",\"shareData\":\"$22\",\"fullTextPdfPath\":\"/svnbmj/7/6/527.full.pdf\",\"copyrightStatement\":\"\"}],[\"$\",\"div\",null,{\"className\":\"col-span-12 mt-2 bg-white md:mt-0\",\"children\":[\"$\",\"div\",null,{\"children\":[\"$\",\"h1\",null,{\"id\":\"article-title-1\",\"className\":\"text-bmj-silver-800 mb-6 text-center text-[1.75rem] font-normal leading-[2.25rem] md:text-left lg:text-[2.625rem] lg:leading-[3.063rem]\",\"data-testid\":\"title\",\"children\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\"}]}]}],[\"$\",\"div\",null,{\"className\":\"bg-white\",\"children\":[[\"$\",\"$L23\",null,{\"affiliations\":\"$Q24\",\"authors\":[{\"authorPosition\":\"first\",\"affiliation\":\"Department of Neurology, Zhongshan Hospital Fudan University, Shanghai, China\",\"author\":{\"role\":null,\"displayName\":\"Zhiyuan Zhou\",\"orcid\":null},\"correspondingAuthor\":\"false\",\"processedAffilitations\":[{\"text\":\"Department of Neurology, Zhongshan Hospital Fudan University, Shanghai, China\",\"index\":1}]},{\"authorPosition\":\"middle\",\"affiliation\":\"Department of Neurology, Zhongshan Hospital Fudan University, Shanghai, China\",\"author\":{\"role\":null,\"displayName\":\"Yuanyuan Ma\",\"orcid\":null},\"correspondingAuthor\":\"false\",\"processedAffilitations\":[{\"text\":\"Department of Neurology, Zhongshan Hospital Fudan University, Shanghai, China\",\"index\":1}]},{\"authorPosition\":\"middle\",\"affiliation\":\"Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China\",\"author\":{\"role\":null,\"displayName\":\"Tongtong Xu\",\"orcid\":null},\"correspondingAuthor\":\"false\",\"processedAffilitations\":[{\"text\":\"Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China\",\"index\":2}]},{\"authorPosition\":\"middle\",\"affiliation\":\"Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China\",\"author\":{\"role\":null,\"displayName\":\"Shengju Wu\",\"orcid\":null},\"correspondingAuthor\":\"false\",\"processedAffilitations\":[{\"text\":\"Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China\",\"index\":2}]},{\"authorPosition\":\"middle\",\"affiliation\":\"Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China\",\"author\":{\"role\":null,\"displayName\":\"Guo-Yuan Yang\",\"orcid\":null},\"correspondingAuthor\":\"false\",\"processedAffilitations\":[{\"text\":\"Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China\",\"index\":2}]},{\"authorPosition\":\"middle\",\"affiliation\":\"Department of Neurology, Zhongshan Hospital Fudan University, Shanghai, China\",\"author\":{\"role\":null,\"displayName\":\"Jing Ding\",\"correspondingEmail\":\"ding.jing@zs-hospital.sh.cn\",\"orcid\":\"http://orcid.org/0000-0001-5135-4210\"},\"correspondingAuthor\":\"true\",\"processedAffilitations\":[{\"text\":\"Department of Neurology, Zhongshan Hospital Fudan University, Shanghai, China\",\"index\":1}]},{\"authorPosition\":\"last\",\"affiliation\":\"Department of Neurology, Zhongshan Hospital Fudan University, Shanghai, China; Department of the State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China\",\"author\":{\"role\":null,\"displayName\":\"Xin Wang\",\"correspondingEmail\":\"wang.xin@zs-hospital.sh.cn\",\"orcid\":null},\"correspondingAuthor\":\"true\",\"processedAffilitations\":[{\"text\":\"Department of Neurology, Zhongshan Hospital Fudan University, Shanghai, China\",\"index\":1},{\"text\":\"Department of the State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai, China\",\"index\":3}]}],\"nonAuthorText\":[]}],[\"$\",\"div\",null,{\"className\":\"mt-6 grid h-12 w-full md:mt-0 md:hidden\",\"data-testid\":\"pdf\",\"children\":[\"$\",\"$L25\",null,{\"doi\":\"10.1136/svn-2022-001594\",\"rightsAndPermissionsData\":\"$20\",\"articlePath\":\"7/6/527\",\"shareData\":\"$22\",\"articleCitationData\":\"$21\",\"copyrightStatement\":\"\",\"licenceStatement\":\"http://creativecommons.org/licenses/by-nc/4.0/http://creativecommons.org/licenses/by-nc/4.0/\",\"fullTextPdfPath\":\"/svnbmj/7/6/527.full.pdf\"}]}]]}],[\"$\",\"div\",null,{\"className\":\"grid grid-cols-[3fr_1fr] gap-x-4 gap-y-4 md:grid-cols-[auto_332px]\",\"children\":[[\"$\",\"div\",null,{\"className\":\"col-span-2 mb-2 pt-[40px] md:mb-6 lg:col-span-1\",\"children\":[\"$\",\"div\",null,{\"children\":[[\"$\",\"div\",\"1\",{\"xmlns\":\"http://www.w3.org/1999/xhtml\",\"className\":\"article fulltext-view flex flex-col -mb-6\",\"children\":[[\"$\",\"$1e\",\"0\",{}],[\"$\",\"$1e\",\"1\",{}],[\"$\",\"div\",\"2\",{\"className\":\"abstract-section\",\"id\":\"abstract-1\",\"children\":[[[\"$\",\"h2\",\"0\",{\"children\":\"Abstract\"}],[\"$\",\"div\",\"1\",{\"id\":\"sec-1\",\"className\":\"subsection\",\"children\":[\"$\",\"p\",null,{\"id\":\"p-2\",\"children\":[[\"$\",\"strong\",\"0\",{\"children\":\"Background\"}],\" Vascular cognitive impairment (VCI) is the second-leading cause of dementia worldwide, which is caused by cerebrovascular diseases or relevant risk factors. However, there are no appropriate animal models, which can be used to study changes of neuropathology in the human VCI. To better understand the development of VCI, we modified three mouse models of chronical vascular diseases, and further compared the advantage and disadvantage of these models. We hope to establish a more suitable mouse model mimicking VCI in human beings.\"]}]}],[\"$\",\"div\",\"2\",{\"id\":\"sec-2\",\"className\":\"subsection\",\"children\":[\"$\",\"p\",null,{\"id\":\"p-3\",\"children\":[[\"$\",\"strong\",\"0\",{\"children\":\"Methods\"}],\" Adult male C57/BL6 mice (n=98) were used and animals underwent transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion, respectively. Haemodynamic changes of surface cerebral blood flow (CBF) were examined up to 4 weeks. Spatial cognitive impairment was evaluated to determine the consequence of chronic cerebral ischaemia.\"]}]}],[\"$\",\"div\",\"3\",{\"id\":\"sec-3\",\"className\":\"subsection\",\"children\":[\"$\",\"p\",null,{\"id\":\"p-4\",\"children\":[[\"$\",\"strong\",\"0\",{\"children\":\"Results\"}],\" These mouse models showed different extents of CBF reduction and spatial reference memory impairment from 1 week up to 4 weeks postoperation compared with the control group (p\u003c0.05). We found that (1) bilaterally ligation of common carotid artery caused decrease of 90% CBF in C57/BL6 mice (p\u003c0.05) and caused acute instead of prolonged impairment of spatial reference memory (p\u003c0.05); (2) unilateral ligation of common carotid artery did not cause severe ipsilateral ischaemia as seen in the tBCCAO mice and caused minor but significant spatial reference memory disturbance (p\u003c0.05); and (3) 20% decrease in the bilateral CBF did not cause spatial reference memory impairment 4 weeks postoperation (p\u003e0.05), while 30% decrease in bilateral or unilateral CBF led to significant memory disturbance in mice (p\u003c0.05).\"]}]}],[\"$\",\"div\",\"4\",{\"id\":\"sec-4\",\"className\":\"subsection\",\"children\":[\"$\",\"p\",null,{\"id\":\"p-5\",\"children\":[[\"$\",\"strong\",\"0\",{\"children\":\"Conclusion\"}],\" We demonstrated that BCAS using 0.16/0.18 mm microcoils is an alternative VCI mouse model when studying the mechanism and developing therapy of VCI.\"]}]}]],[\"$\",\"$L26\",null,{\"targetId\":\"article-title-1\"}]]}],[\"$\",\"$1e\",\"3\",{}],[\"$\",\"div\",null,{\"className\":\"section notes text-bmj-silver-800 border-bmj-silver-100 [\u0026_h3]:text-bmj-silver-800 mb-[40px] border-[1px] px-[24px] pt-[8px] pb-[16px] [\u0026_p]:my-[8px] [\u0026_ul]:m-0 [\u0026_ul]:list-none [\u0026_ul]:p-0 [\u0026_li]:m-0 [\u0026_li]:p-0 [\u0026_h3]:mb-0 [\u0026_h3]:mt-[16px] [\u0026_h3]:text-[1.25rem] [\u0026_h3]:font-normal\",\"children\":[\"$\",\"div\",null,{\"data-testid\":\"article-notes-content\",\"className\":\"article-notes-content\",\"children\":[\"$\",\"div\",null,{\"className\":\"\",\"id\":\"boxed-text-1\",\"children\":[[\"$\",\"div\",\"0\",{\"id\":\"sec-5\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"What is already known on this topic\"}],[\"$\",\"ul\",\"1\",{\"className\":\"list-unord \",\"id\":\"list-1\",\"children\":[\"$\",\"li\",null,{\"id\":\"list-item-1\",\"children\":[\"$\",\"p\",null,{\"id\":\"p-6\",\"children\":\"Cerebral ischaemia or hypoperfusion leads to cognitive impairment in experimental mouse models.\"}]}]}]]}],[\"$\",\"div\",\"1\",{\"id\":\"sec-6\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"What this study adds\"}],[\"$\",\"ul\",\"1\",{\"className\":\"list-unord \",\"id\":\"list-2\",\"children\":[\"$\",\"li\",null,{\"id\":\"list-item-2\",\"children\":[\"$\",\"p\",null,{\"id\":\"p-7\",\"children\":\"This study elucidates different cerebral ischaemia and spatial cognitive impairment patterns in three common vascular cognitive impairment (VCI) mouse models.\"}]}]}]]}],[\"$\",\"div\",\"2\",{\"id\":\"sec-7\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"How this study might affect research, practice and/or policy\"}],[\"$\",\"ul\",\"1\",{\"className\":\"list-unord \",\"id\":\"list-3\",\"children\":[\"$\",\"li\",null,{\"id\":\"list-item-3\",\"children\":[\"$\",\"p\",null,{\"id\":\"p-8\",\"children\":\"Researchers can use 0.16/0.18 mm bilateral common carotid artery stenosis as an alternative VCI mouse model when they study the mechanism and the development of VCI therapy.\"}]}]}]]}]]}]}]}],[\"$\",\"div\",null,{\"className\":\"article-body-sections wrap-urls md:[\u0026_h2]:text-[2.125rem]\",\"data-testid\":\"article-body-section\",\"children\":[[\"$\",\"section\",\"sec-8\",{\"id\":\"sec-8\",\"children\":[[\"$\",\"h2\",\"0\",{\"className\":\"\",\"children\":\"Introduction\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-9\",\"children\":[\"Vascular cognitive impairment (VCI) represents the second-leading cause of dementia after Alzheimer’s disease, accounting for 15%–40% of all dementia cases.\",[\"$\",\"a\",\"1\",{\"id\":\"xref-ref-1-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-1\",\"children\":\"1 2\"}],\" The development of VCI is a complex consequence of various cardiovascular and cerebrovascular events, such as cerebral small vessel disease, multi-infarct dementia, strategic infarct, severe hypoperfusion, hereditary vasculopathy and other haemorrhagic cerebrovascular diseases.\",[\"$\",\"a\",\"3\",{\"id\":\"xref-ref-3-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-3\",\"children\":\"3 4\"}],\" In VCI patients, the main cerebrovascular pathologies are usually cortical and subcortical micro, multiple infarcts and white matter hyperintensities due to chronic or/and acute compromised cerebral blood flow (CBF) in the whole brain or specific brain regions. The other neuropathophysiological changes include: brain–blood barrier breakdown, myelin loss, arteriolosclerosis, leptomeningeal cerebral amyloid angiopathy and perivascular space dilation, etc.\",[\"$\",\"a\",\"5\",{\"id\":\"xref-ref-5-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-5\",\"children\":\"5 6\"}],\" Although much has known about VCI, the precise mechanism that how these neurovascular pathologies translate to cognitive function decline remains unrevealed.\"]}],[\"$\",\"p\",\"2\",{\"id\":\"p-10\",\"children\":[\"Currently, more than 16 rodents experimental models have been developed to mimic neuropathological features and symptoms of human VCI.\",[\"$\",\"a\",\"1\",{\"id\":\"xref-ref-7-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-7\",\"children\":\"7\"}],\" Usually, most experimental VCI models depended on generating chronic cerebral hypoperfusion (CCH) condition, resulting in white matter injury, neuronal loss, axonal damage and cognitive impairment in animals.\",[\"$\",\"a\",\"3\",{\"id\":\"xref-ref-7-2\",\"className\":\"xref-bibr\",\"href\":\"#ref-7\",\"children\":\"7 8\"}],\" Apart from CCH, some studies found transient cerebral hypoperfusion could also cause acute or remote neurological damage and subsequently resulted in cognitive impairment.\",[\"$\",\"a\",\"5\",{\"id\":\"xref-ref-9-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-9\",\"children\":\"9\"}],\" Although CCH is a key mechanism leading to VCI and dementia, none of CCH models could replicate all neuropathological abnormalities in VCI patients because simply blocking or narrowing major cervical artery could not completely cause real cerebral ischaemia pattern occurring in VCI patients.\",[\"$\",\"a\",\"7\",{\"id\":\"xref-ref-10-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-10\",\"children\":\"10\"}],\" Therefore, it is necessary to know the different characteristic of these experimental animal models for selecting an better model for experimental studies and clinical translation of drugs and therapies.\"]}],[\"$\",\"p\",\"3\",{\"id\":\"p-11\",\"children\":[\"Among all animals, rodent species, especially C57/BL6 mouse strain were preferred to be used to establish VCI model because of many advantages: such as less drug dosage, easier handling, and more importantly, higher vulnerability to cerebral ischaemia because of incomplete circle of Willis.\",[\"$\",\"a\",\"1\",{\"id\":\"xref-ref-11-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-11\",\"children\":\"11\"}],\" Therefore, this study established three commonly used experimental mouse models of VCI using C57/BL6 mouse strain by ligation or stenosis of common carotid arteries (CCAs), namely transient bilateral common carotid arteries occlusion (tBCCAO), or bilateral common carotid artery stenosis (BCAS), or right unilateral common carotid artery occlusion (rUCCAO). For BCAS models, we set three subgroups according to different extents of CCA stenosis caused by microcoils with different inner diameters (ID, eg, bilateral 0.16 mm, 0.16/0.18 mm and bilateral 0.18 mm). We aimed to clarify which mouse model is more appropriate to induce chronic brain ischaemia and closely mimicking the CBF changes of VCI patients, providing a valuable scientific research tool to elucidate the pathophysiology and develop therapeutic strategy for VCI in human.\"]}]]}],[\"$\",\"$L26\",null,{\"targetId\":\"article-title-1\"}]]}],[\"$\",\"div\",null,{\"className\":\"article-body-sections wrap-urls md:[\u0026_h2]:text-[2.125rem]\",\"data-testid\":\"article-body-section\",\"children\":[[\"$\",\"section\",\"sec-9\",{\"id\":\"sec-9\",\"children\":[[\"$\",\"h2\",\"0\",{\"className\":\"\",\"children\":\"Materials and methods\"}],[\"$\",\"div\",\"1\",{\"id\":\"sec-10\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"Animal experimental design\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-12\",\"children\":\"Animal studies were reported following ARRIVE guidelines. Adult male C57/BL6 mice (8 weeks, weight 22–24 g) were provided by Beijing Vital River Laboratory Animal Technology. Mice were acclimatised for 1 week before operation. Mice were housed at 22 °C with 60% humidity and were provided ad libitum access to food and water. For CBF analysis, each experimental model’s CBF was compared with the preoperation baseline, so no control group was included. For cognitive function analysis, each model was compared with sham-operation. The experimental unit was single mouse. A total number of 118 mice were used for this study, 20 mice failed to survive from the operation because of severe cerebral ischaemia. The remaining 98 mice were further used for the whole experiment.\"}]]}],[\"$\",\"div\",\"2\",{\"id\":\"sec-11\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"Bilateral common carotid artery stenosis\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-13\",\"children\":\"$27\"}]]}],[\"$\",\"div\",\"3\",{\"id\":\"sec-12\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"tBCCAO and rUCCAO\"}],[\"$\",\"div\",\"1\",{\"id\":\"sec-13\",\"className\":\"subsection\",\"children\":[[\"$\",\"h4\",\"0\",{\"children\":\"Transient bilateral common carotid artery occlusion\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-14\",\"children\":\"Anesthetisation procedure was same as the BCAS model. The right and left CCAs were isolated from the adjacent nerves and surrounding sheaths, and both CCAs were occluded with microvascular clips (RWD life sciences, Shenzhen, China) for 20 min. Then the clips were removed to allow CBF reperfusion and incisions were sutured. Mice in the control group were sham-operated for 20 min without occlusion of CCAs. After the operation, mice were kept in their quarters with food and water available ad libitum.\"}]]}],[\"$\",\"div\",\"2\",{\"id\":\"sec-14\",\"className\":\"subsection\",\"children\":[[\"$\",\"h4\",\"0\",{\"children\":\"Right unilateral common carotid artery occlusion\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-15\",\"children\":\"Mice were administered and fixed on the operation table on supine position. The right CCA was isolated from the adjacent nerves and ligated with a 6–0 silk suture to achieve rUCCAO. A total number of 62 mice were used for the operation, in which 4 mice died during the operation because of severe cerebral ischaemia, the survived mice were used for the following experiments (tBCCAO group, n=33; rUCCAO group, n=12; control group, n=13).\"}]]}]]}],[\"$\",\"div\",\"4\",{\"id\":\"sec-15\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"Surface CBF measurement\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-16\",\"children\":[\"The surface CBF of each time point of animal models were measured by laser Doppler flowmetry (Moor Instruments, Devon, UK). The measurement method of the surface CBF was described as our previous study.\",[\"$\",\"a\",\"1\",{\"id\":\"xref-ref-12-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-12\",\"children\":\"12\"}],\" Briefly, mice were anaesthetised with isoflurane and their scalp was cut to expose the skull. The detector was then placed on the skull 1 mm posterior and 2 mm lateral to the bregma and held for a few seconds until the floating CBF value was stabilised. Then, the CBF value was recorded, and the scalp was sutured.\"]}]]}],[\"$\",\"div\",\"5\",{\"id\":\"sec-16\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"Laser speckle contrast imaging\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-17\",\"children\":[\"Laser speckle contrast imaging (LSCI) measurement method was described as our previous study.\",[\"$\",\"a\",\"1\",{\"id\":\"xref-ref-13-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-13\",\"children\":\"13\"}],\" Briefly, mice were anaesthetised and heads were fixed in a stereotaxic frame. Then mice were placed under the LSCI equipment (RFLSI Pro, RWD life sciences, Shenzhen, China). The scalp of mice were cut by surgical scissors and the surface of the skulls were exposed and illuminated with a 784 nm/32 mW laser with a beam expander and light intensity was controlled by a polariser. The CBF images were detected by a CCD camera and the image acquisitions were performed using custom software (RWD life science). Three hundred frames were acquired at 10 Hz with 10 ms exposure time.\"]}]]}],[\"$\",\"div\",\"6\",{\"id\":\"sec-17\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"Morris water maze test\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-18\",\"children\":[\"The Morris water maze (MWM) protocol in this study was followed by Vorhees \",[\"$\",\"em\",\"1\",{\"children\":\"et al\"}],\".\",[\"$\",\"a\",\"3\",{\"id\":\"xref-ref-14-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-14\",\"children\":\"14\"}],\"$28\"]}]]}],[\"$\",\"div\",\"7\",{\"id\":\"sec-18\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"Statistical analysis\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-19\",\"children\":[\"All statistical analyses were performed using the GraphPad Prism V.8.0 (GraphPad Software, San Diego, USA). The normality of all data was analysed by D'Agostino and Pearson omnibus normality test. The significance of differences was determined by one-way analysis of variance, followed by multiple comparisons between the control group and experimental model groups. All values were presented as mean±SEM \",[\"$\",\"em\",\"1\",{\"children\":\"P\"}],\"＜0.05 was consider significant difference. *Indicated p＜0.05; **indicated p＜0.01; ***indicated p＜0.001.\"]}],[\"$\",\"div\",\"2\",{\"id\":\"sec-19\",\"className\":\"subsection\",\"children\":[[\"$\",\"h4\",\"0\",{\"children\":\"Randomisation\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-20\",\"children\":\"No randomisation method was used in this study, animals were open-labelled according to the number registered in Anymaze software.\"}]]}],[\"$\",\"div\",\"3\",{\"id\":\"sec-20\",\"className\":\"subsection\",\"children\":[[\"$\",\"h4\",\"0\",{\"children\":\"Inclusion and exclusion criteria of animals\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-21\",\"children\":\"The assays of CBF changes and cognitive impairment were exploratory in this study, so no inclusion and exclusion criteria were used.\"}]]}]]}]]}],[\"$\",\"$L26\",null,{\"targetId\":\"article-title-1\"}]]}],[\"$\",\"div\",null,{\"className\":\"article-body-sections wrap-urls md:[\u0026_h2]:text-[2.125rem]\",\"data-testid\":\"article-body-section\",\"children\":[[\"$\",\"section\",\"sec-21\",{\"id\":\"sec-21\",\"children\":[[\"$\",\"h2\",\"0\",{\"className\":\"\",\"children\":\"Results\"}],[\"$\",\"div\",\"1\",{\"id\":\"sec-22\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"CBF changes in three cerebral hypoperfusion models\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-22\",\"children\":[\"We first examined haemodynamic changes in BCAS mice. BCAS subgroups operation procedure was shown in \",[\"$\",\"a\",\"1\",{\"id\":\"xref-fig-1-1\",\"className\":\"xref-fig\",\"href\":\"#F1\",\"children\":\"figure 1A\"}],\". The representation of CBF change detected by LSCI for each BCAS subgroup was shown in \",[\"$\",\"a\",\"3\",{\"id\":\"xref-fig-1-2\",\"className\":\"xref-fig\",\"href\":\"#F1\",\"children\":\"figure 1B\"}],\". We found that the CBF in 0.16 mm group reduced to bilaterally 45%–50% of baseline postoperation, recovered to about 60% after 1 week and reached 70% of the baseline after 4 weeks (\",[\"$\",\"a\",\"5\",{\"id\":\"xref-fig-1-3\",\"className\":\"xref-fig\",\"href\":\"#F1\",\"children\":\"figure 1C\"}],\"). In mice of 0.16/0.18 mm group, the CBF of the right hemisphere (subject to ID=0.16 mm microcoil) declined to 45%–50% of baseline level postoperation and gradually recovered to 65%–70% after 4 weeks. The CBF of left hemisphere (subject to ID=0.18 mm microcoil) decreased to 55%–60% postoperation and gradually recovered to 70% 4 weeks later (\",[\"$\",\"a\",\"7\",{\"id\":\"xref-fig-1-4\",\"className\":\"xref-fig\",\"href\":\"#F1\",\"children\":\"figure 1D\"}],\"). In mice of 0.18 mm group, CBF decreased bilaterally to 60%–65% of baseline postoperation, and then gradually recovered to about 80% of baseline by the fourth week (\",[\"$\",\"a\",\"9\",{\"id\":\"xref-fig-1-5\",\"className\":\"xref-fig\",\"href\":\"#F1\",\"children\":\"figure 1E\"}],\"). The rUCCAO and tBCCAO operation procedures were shown in \",[\"$\",\"a\",\"11\",{\"id\":\"xref-fig-2-1\",\"className\":\"xref-fig\",\"href\":\"#F2\",\"children\":\"figure 2A\"}],\". The representations of CBF change detected by LSCI for rUCCAO and tBCCAO mice were shown in \",[\"$\",\"a\",\"13\",{\"id\":\"xref-fig-2-2\",\"className\":\"xref-fig\",\"href\":\"#F2\",\"children\":\"figure 2B\"}],\". In mice of rUCCAO group, the CBF was reduced to around 55% of baseline while the contralateral CBF reduced about 10%–15% compared with preoperation. One-week postoperation, ipsilateral CBF returned to 75%–80% and the contralateral CBF recovered to baseline level. Four weeks later, the ipsilateral CBF recovered to 80% of baseline level and contralateral CBF stayed nearly 100% (\",[\"$\",\"a\",\"15\",{\"id\":\"xref-fig-2-3\",\"className\":\"xref-fig\",\"href\":\"#F2\",\"children\":\"figure 2C\"}],\"). In mice of tBCCAO group, the bilateral CBF decreased to approximately 10% of baseline level and returned to 100% after releasing vascular clamps. The bilateral CBF showed no significant difference from the first to the fourth week (\",[\"$\",\"a\",\"17\",{\"id\":\"xref-fig-2-4\",\"className\":\"xref-fig\",\"href\":\"#F2\",\"children\":\"figure 2D\"}],\").\"]}],[\"$\",\"$L29\",\"2\",{\"attributes\":{\"id\":\"F1\",\"className\":\"fig pos-float odd\"},\"highQualityImageUrl\":\"/content/svnbmj/7/6/527/F1.large.jpg\",\"thumbnailImageUrl\":\"/content/svnbmj/7/6/527/F1.medium.gif\",\"title\":\"Figure 1\",\"description\":\"CBF changes and mortalities of BCAS models (A) Schematic representation of BCAS operation (grouping by different inner diameters of the microcoils). (B) Representation of laser speckle contrast image on BCAS model subgroups at preoperation, 2 hours postoperation, and 1 week, 2 weeks, 4 weeks postoperation. (C–E) Numerical representation of CBF changes measured by laser Doppler flowmetry at preoperation, 2 hours postoperation, and 1 week, 2 weeks, 3 weeks and 4 weeks postoperation. (C) The 0.16 mm subgroup of the BCAS model. (D) The 0.16/0.18 mm subgroup of the BCAS model. (E) The 0.18 mm subgroup of the BCAS model. n=5/group. (F) The mortality of different subgroups. All data were represented as mean±SEM. ***P\u0026lt;0.001. BCAS, bilateral common carotid artery stenosis; CBF, cerebral blood flow.\",\"rightsAndPermissionsData\":{\"id\":\"svnbmj\",\"title\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\",\"licenseUrl\":\"http://creativecommons.org/licenses/by-nc/4.0/\",\"accessType\":\"open-access\",\"isOpenAccess\":\"true\",\"publicationDateTimestamp\":\"2022-12-20\",\"authorList\":\"Zhiyuan Zhou, Yuanyuan Ma, Tongtong Xu, Shengju Wu, Guo-Yuan Yang, Jing Ding, Xin Wang\",\"volume\":\"7\",\"issue\":\"6\",\"firstPage\":\"527\",\"lastPage\":\"533\"},\"doi\":\"10.1136/svn-2022-001594\",\"oa\":\"CC-BY-NC-4.0\"}],[\"$\",\"$L29\",\"3\",{\"attributes\":{\"id\":\"F2\",\"className\":\"fig pos-float odd\"},\"highQualityImageUrl\":\"/content/svnbmj/7/6/527/F2.large.jpg\",\"thumbnailImageUrl\":\"/content/svnbmj/7/6/527/F2.medium.gif\",\"title\":\"Figure 2\",\"description\":\"Cerebral blood flow (CBF) changes and mortalities of right unilateral common carotid artery occlusion (rUCCAO) and transient bilateral common carotid arteries occlusion (tBCCAO) models (A) Schematic representation of tBCCAO and rUCCAO operation. (B) Representation of laser speckle contrast image of rUCCAO and tBCCAO models at preoperation, 2 hours postoperation (rUCCAO)/immediately postoperation (tBCCAO), and 1 week, 2 weeks, 4 weeks postoperation. (C–D) Numerical representation of CBF changes measured by laser Doppler flowmetry (LDF) at preoperation, 2 hours postoperation (rUCCAO)/immediately postoperation (tBCCAO), and 1 week, 2 weeks, 3 weeks and 4 weeks postoperation. n=5/group. (C) rUCCAO. (D) tBCCAO. (E) Mortalities of tBCCAO and rUCCAO operation. All data were represented as mean±SEM. ns indicated not significant.\",\"rightsAndPermissionsData\":{\"id\":\"svnbmj\",\"title\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\",\"licenseUrl\":\"http://creativecommons.org/licenses/by-nc/4.0/\",\"accessType\":\"open-access\",\"isOpenAccess\":\"true\",\"publicationDateTimestamp\":\"2022-12-20\",\"authorList\":\"Zhiyuan Zhou, Yuanyuan Ma, Tongtong Xu, Shengju Wu, Guo-Yuan Yang, Jing Ding, Xin Wang\",\"volume\":\"7\",\"issue\":\"6\",\"firstPage\":\"527\",\"lastPage\":\"533\"},\"doi\":\"10.1136/svn-2022-001594\",\"oa\":\"CC-BY-NC-4.0\"}]]}],[\"$\",\"div\",\"2\",{\"id\":\"sec-23\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"Mortality\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-25\",\"children\":[\"The mortality of 0.16 mm, 0.16/0.18 mm and 0.18 mm group in the BCAS model reached nearly 75%, 20% and around 15%, respectively (\",[\"$\",\"a\",\"1\",{\"id\":\"xref-fig-1-6\",\"className\":\"xref-fig\",\"href\":\"#F1\",\"children\":\"figure 1E\"}],\"). The mortality of rUCCAO and 20 min-tBCCAO models was both around 10% (\",[\"$\",\"a\",\"3\",{\"id\":\"xref-fig-2-5\",\"className\":\"xref-fig\",\"href\":\"#F2\",\"children\":\"figure 2E\"}],\").\"]}]]}],[\"$\",\"div\",\"3\",{\"id\":\"sec-24\",\"className\":\"subsection\",\"children\":[[\"$\",\"h3\",\"0\",{\"children\":\"Spatial reference memory and study function\"}],[\"$\",\"div\",\"1\",{\"id\":\"sec-25\",\"className\":\"subsection\",\"children\":[[\"$\",\"h4\",\"0\",{\"children\":\"Bilateral common carotid artery stenosis\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-26\",\"children\":[\"Four weeks’ postoperation, the spatial reference study and memory of the 0.18 mm group was not statistically different compared with the control group (\",[\"$\",\"a\",\"1\",{\"id\":\"xref-fig-3-1\",\"className\":\"xref-fig\",\"href\":\"#F3\",\"children\":\"figure 3A–D\"}],\"), while both 0.16 mm and 0.16/0.18 mm group showed significantly impairment of cognitive function as evidenced by a slower study rate to locate the platform (\",[\"$\",\"a\",\"3\",{\"id\":\"xref-fig-3-2\",\"className\":\"xref-fig\",\"href\":\"#F3\",\"children\":\"figure 3A\"}],\") and less time spent in the target quadrant as well as less crosses to the platform area (\",[\"$\",\"a\",\"5\",{\"id\":\"xref-fig-3-3\",\"className\":\"xref-fig\",\"href\":\"#F3\",\"children\":\"figure 3B,C\"}],\"). Notably, mice in 0.18 mm and 0.16/0.18 mm groups showed no motor ability impairment after 4 weeks, while mice in 0.16 mm group showed motor ability impairment evaluated by the swimming speed (\",[\"$\",\"a\",\"7\",{\"id\":\"xref-fig-3-4\",\"className\":\"xref-fig\",\"href\":\"#F3\",\"children\":\"figure 3D\"}],\").\"]}]]}],[\"$\",\"div\",\"2\",{\"id\":\"sec-26\",\"className\":\"subsection\",\"children\":[[\"$\",\"h4\",\"0\",{\"children\":\"Transient bilateral common carotid arteries occlusion\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-27\",\"children\":[\"Mice underwent tBCCAO showed significant decline in spatial reference study function at first and second weeks’ postoperation. However, 4 weeks’ postoperation, the performance of tBCCAO mice in MWM was not significantly different from that of the control group (\",[\"$\",\"a\",\"1\",{\"id\":\"xref-fig-4-1\",\"className\":\"xref-fig\",\"href\":\"#F4\",\"children\":\"figure 4A–C\"}],\"). The tBCCAO mice did not show any impairment in motor ability in this experiment, as evidenced by no reduction in the swimming speed compared with the control group (\",[\"$\",\"a\",\"3\",{\"id\":\"xref-fig-4-2\",\"className\":\"xref-fig\",\"href\":\"#F4\",\"children\":\"figure 4D\"}],\").\"]}],[\"$\",\"$L29\",\"2\",{\"attributes\":{\"id\":\"F3\",\"className\":\"fig pos-float odd\"},\"highQualityImageUrl\":\"/content/svnbmj/7/6/527/F3.large.jpg\",\"thumbnailImageUrl\":\"/content/svnbmj/7/6/527/F3.medium.gif\",\"title\":\"Figure 3\",\"description\":\"Test of spatial reference memory and motor ability deficiency of BCAS model subgroups (A) Morris water maze (MWM) acquisition period for subgroups of the BCAS model from the starting day 1 to day 5 of the test. (B) MWM probe test on day 6. (C) Times of each mouse swimming across the platform area in probe test. (D) Times of each mouse swimming across the platform area in probe test. (E) Average swimming speed of each group on day 6. All groups were compared with the control group. All data were represented as mean±SEM. ns indicated not significant; *p＜0.05; **p＜0.01; **p＜0.001. 0.16 mm subgroup (n=7); 0.16/0.18 mm subgroup (n=10); 0.18 mm subgroup (n=11); control group (n=12). BCAS, bilateral common carotid artery stenosis.\",\"rightsAndPermissionsData\":{\"id\":\"svnbmj\",\"title\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\",\"licenseUrl\":\"http://creativecommons.org/licenses/by-nc/4.0/\",\"accessType\":\"open-access\",\"isOpenAccess\":\"true\",\"publicationDateTimestamp\":\"2022-12-20\",\"authorList\":\"Zhiyuan Zhou, Yuanyuan Ma, Tongtong Xu, Shengju Wu, Guo-Yuan Yang, Jing Ding, Xin Wang\",\"volume\":\"7\",\"issue\":\"6\",\"firstPage\":\"527\",\"lastPage\":\"533\"},\"doi\":\"10.1136/svn-2022-001594\",\"oa\":\"CC-BY-NC-4.0\"}],[\"$\",\"$L29\",\"3\",{\"attributes\":{\"id\":\"F4\",\"className\":\"fig pos-float odd\"},\"highQualityImageUrl\":\"/content/svnbmj/7/6/527/F4.large.jpg\",\"thumbnailImageUrl\":\"/content/svnbmj/7/6/527/F4.medium.gif\",\"title\":\"Figure 4\",\"description\":\"Test of spatial reference memory and motor ability deficiency of right unilateral common carotid artery occlusion (rUCCAO) and transient bilateral common carotid arteries occlusion (tBCCAO) models. (A) Morris water maze (MWM) acquisition period for tBCCAO at 1 week, 2 weeks and 4 weeks after operation from day 1 to day 5. (B) MWM probe test on day 6. The time each mouse swimming in the quadrant including the platform area. (C) The time each mouse swimming across the platform area in probe test. (D) Average swimming speed of each group on day 6. All data were represented as mean±SEM. All groups were compared with the control group. NS indicated not significant; *p＜0.05; **p＜0.01; ***p＜0.001. tBCCAO 1 week, 2 weeks, 4 weeks group (n=11/group); rUCCAO group (n=12); control group (n=13).\",\"rightsAndPermissionsData\":{\"id\":\"svnbmj\",\"title\":\"Deeper cerebral hypoperfusion leads to spatial cognitive impairment in mice\",\"licenseUrl\":\"http://creativecommons.org/licenses/by-nc/4.0/\",\"accessType\":\"open-access\",\"isOpenAccess\":\"true\",\"publicationDateTimestamp\":\"2022-12-20\",\"authorList\":\"Zhiyuan Zhou, Yuanyuan Ma, Tongtong Xu, Shengju Wu, Guo-Yuan Yang, Jing Ding, Xin Wang\",\"volume\":\"7\",\"issue\":\"6\",\"firstPage\":\"527\",\"lastPage\":\"533\"},\"doi\":\"10.1136/svn-2022-001594\",\"oa\":\"CC-BY-NC-4.0\"}]]}],[\"$\",\"div\",\"3\",{\"id\":\"sec-27\",\"className\":\"subsection\",\"children\":[[\"$\",\"h4\",\"0\",{\"children\":\"Right unilateral common carotid artery occlusion\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-30\",\"children\":[\"The rUCCAO mice showed mixed results. In the acquisition period, mice showed a longer time to find the platform compared with that in the control group, while they behaved almost as good as the control group in the probe text (\",[\"$\",\"a\",\"1\",{\"id\":\"xref-fig-4-3\",\"className\":\"xref-fig\",\"href\":\"#F4\",\"children\":\"figure 4B,C\"}],\"). Similarly, rUCCAO mice showed no motor ability impairment (\",[\"$\",\"a\",\"3\",{\"id\":\"xref-fig-4-4\",\"className\":\"xref-fig\",\"href\":\"#F4\",\"children\":\"figure 4D\"}],\").\"]}]]}]]}]]}],[\"$\",\"$L26\",null,{\"targetId\":\"article-title-1\"}]]}],[\"$\",\"div\",null,{\"className\":\"article-body-sections wrap-urls md:[\u0026_h2]:text-[2.125rem]\",\"data-testid\":\"article-body-section\",\"children\":[[\"$\",\"section\",\"sec-28\",{\"id\":\"sec-28\",\"children\":[[\"$\",\"h2\",\"0\",{\"className\":\"\",\"children\":\"Discussion\"}],[\"$\",\"p\",\"1\",{\"id\":\"p-31\",\"children\":\"In this study, we compared three common mouse VCI models by acute or chronic restriction of CBF. Our results showed that: (1) Bilaterally ligation of CCAs caused 90% CBF decrease in C57/BL6 mice and caused acute instead of prolonged impairment of spatial reference memory; (2) Unilateral ligation of the CCA did not cause as severe ipsilateral ischaemia as seen in tBCCAO mice but caused significant spatial memory disturbance and (3) Narrowing the CCAs by half of its diameters (ID: 0.18 mm) caused approximately 20% decrease after collateral compensatory, but did not lead to spatial reference memory after 4 weeks’ postoperation detected by MWM paradigm. However, narrowing 75% of CCAs (ID: 0.16 mm) caused severe spatial cognitive and motor function impairment with a very high mortality rate in C57/BL6 mice; (4) Both mice in 0.16/0.18 mm and 0.18 mm groups caused significant spatial cognitive impairment with only mild mortality.\"}],[\"$\",\"p\",\"2\",{\"id\":\"p-32\",\"children\":[\"Mouse species was preferred by researchers in the field of cerebral ischaemia/hypoperfusion compared with rats due to its unique advantages, such as more vulnerability to cerebral ischaemia and easier gene modification.\",[\"$\",\"a\",\"1\",{\"id\":\"xref-ref-9-2\",\"className\":\"xref-bibr\",\"href\":\"#ref-9\",\"children\":\"9 15\"}],\" As mouse stain could not survive from the permanent BCCA ligation,\",[\"$\",\"a\",\"3\",{\"id\":\"xref-ref-11-2\",\"className\":\"xref-bibr\",\"href\":\"#ref-11\",\"children\":\"11\"}],\" temporary ligation of CCAs was a common procedure to construct VCI in mice in many studies.\",[\"$\",\"a\",\"5\",{\"id\":\"xref-ref-16-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-16\",\"children\":\"16\"}],\" Studies using the tBCCAO model demonstrated that a 5–20 min ligation of bilateral whole-brain ischaemia caused obvious neuropath physiological changes, such as blood–brain barrier breakdown, white matter injury and early or late hippocampal neuronal damage,\",[\"$\",\"a\",\"7\",{\"id\":\"xref-ref-5-2\",\"className\":\"xref-bibr\",\"href\":\"#ref-5\",\"children\":\"5 17 18\"}],\" as well as decreased spatial memory and learning function.\",[\"$\",\"a\",\"9\",{\"id\":\"xref-ref-19-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-19\",\"children\":\"19\"}],\" In our study, mice subject to bilateral transient whole-brain ischaemia showed about 90% reduction of CBF along with acute (up to 2 weeks’ postoperation) but restorable (restored after 4 weeks) spatial cognitive impairment. Some other studies also found a decline in spatial reference memory of tBCCAO and suggested that this decline was related to delayed damage of hippocampal neurons, especially in the CA1 area.\",[\"$\",\"a\",\"11\",{\"id\":\"xref-ref-18-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-18\",\"children\":\"18 19\"}],\" Although the advantages of the tBCCAO model, it lacked major similitude of the real disease state because rare VCI patients were caused by single anterior-circulation ischaemia. Moreover, 20 min tBCCAO did not precisely mimic the humbler diminishments in CBF seen in CCH conditions related to human VCI caused by CCH where CBF might only be reduced by 20%–30%.\",[\"$\",\"a\",\"13\",{\"id\":\"xref-ref-20-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-20\",\"children\":\"20\"}],\"\\n\"]}],[\"$\",\"p\",\"3\",{\"id\":\"p-33\",\"children\":[\"The rUCCAO model was proposed by Japanese scholar Yoshizaki \",[\"$\",\"em\",\"1\",{\"children\":\"et al\"}],\" as an experimental mouse model of CCH.\",[\"$\",\"a\",\"3\",{\"id\":\"xref-ref-21-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-21\",\"children\":\"21\"}],\" The rUCCAO model has numerous advantages compared with other models, such as more consistent CBF decrease among subjects due to easy operation, lower mortality and higher consistency within the same group. This study confirmed that the ipsilateral CBF dropped to 55% of baseline after ligation and gradually recovered to 80% after 4 weeks’ postoperation, which was much similar to that of mice in the 0.18 mm group of BCAS model. In addition, the impairment of spatial reference memory function in both of these two models was insignificant. However, other studies found that rUCCAO mice showed impaired cognitive function evaluated by novel object recognition and MWM tests.\",[\"$\",\"a\",\"5\",{\"id\":\"xref-ref-22-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-22\",\"children\":\"22 23\"}],\" The difference between our study and others still is unknown and needs to be further investigated.\"]}],[\"$\",\"p\",\"4\",{\"id\":\"p-34\",\"children\":[\"The mouse BCAS model was first established in 2004 with a better simulation of clinical BCCA stenosis without causing significant visual function impairment.\",[\"$\",\"a\",\"1\",{\"id\":\"xref-ref-24-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-24\",\"children\":\"24\"}],\" Therefore, it was soon became the widely used model for the research of CCH, white matter injury and VCI.\",[\"$\",\"a\",\"3\",{\"id\":\"xref-ref-25-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-25\",\"children\":\"25 26\"}],\"\\n\"]}],[\"$\",\"p\",\"5\",{\"id\":\"p-35\",\"children\":[\"It is true that Ihara had explored the CBF reduction in BCAS mice induced by different diameter microcoils (0.16, 0.18, 0.20 and 0.22 mm).\",[\"$\",\"a\",\"1\",{\"id\":\"xref-ref-24-2\",\"className\":\"xref-bibr\",\"href\":\"#ref-24\",\"children\":\"24\"}],\" However, previous studies showed that the BCAS model induced by 0.18 mm diameter microcoils could not induce consistent CBF reduction,\",[\"$\",\"a\",\"3\",{\"id\":\"xref-ref-27-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-27\",\"children\":\"27 28\"}],\" which limited its clinical translation. Currently, 0.16 mm and 0.18 mm diameter microcoils were most widely, while few 0.17 mm diameter microcoils were used to establish the BCAS mouse models.\",[\"$\",\"a\",\"5\",{\"id\":\"xref-ref-24-3\",\"className\":\"xref-bibr\",\"href\":\"#ref-24\",\"children\":\"24 29–31\"}],\" Therefore, we chose 0.16 mm and 0.18 mm diameter microcoils to induce the BCAS models in this study. Since mice underwent chronic brain ischaemia induced by 0.16 mm diameter microcoils showed a high mortality (75%),\",[\"$\",\"a\",\"7\",{\"id\":\"xref-ref-32-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-32\",\"children\":\"32\"}],\"$2a\",[\"$\",\"a\",\"9\",{\"id\":\"xref-ref-20-2\",\"className\":\"xref-bibr\",\"href\":\"#ref-20\",\"children\":\"20 33\"}],\" Therefore, we assumed that the 0.16/0.18 mm BCAS model was an appropriate alternative for VCI study.\"]}],[\"$\",\"p\",\"6\",{\"id\":\"p-36\",\"children\":[\"In this study, animal surgery was operated by the same experienced surgeon. All raw data were presented as mean±SEM. In addition, previous study reported similar mortality of mice with BCAS surgeries induced by 0.16 mm and 0.18 mm diameter microcoils, respectively.\",[\"$\",\"a\",\"1\",{\"id\":\"xref-ref-24-4\",\"className\":\"xref-bibr\",\"href\":\"#ref-24\",\"children\":\"24\"}],\" Thus, although it exists bigger differential mortality among 16 mm group (75%), 0.16/01.8 mm group (20%) and 0.18 mm group (15%), our results were truly reflecting the effect of different diameter microcoils on CBF reduction and brain damage.\"]}],[\"$\",\"p\",\"7\",{\"id\":\"p-37\",\"children\":[\"MWM is the most widely employed behavioural test for assessing spatial cognitive function deficits. MWM is also an important behavioural paradigm for drug, molecular, and gene screening in bench studies because of its relatively good objectivity and consistency without causing injury to animals.\",[\"$\",\"a\",\"1\",{\"id\":\"xref-ref-34-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-34\",\"children\":\"34\"}],\" However, this study only focused on deficits in spatially reference memory 4 weeks’ postoperation and lacked exploring other dimensions of cognitive function using more paradigms, such as spatial working memory or fear-based memory. Different cognitive paradigms usually reflected impairments in different brain regions. For example, spatial working memory mainly depended on integrity of white matter while spatial memory was more on decoding function of hippocampus.\",[\"$\",\"a\",\"3\",{\"id\":\"xref-ref-35-1\",\"className\":\"xref-bibr\",\"href\":\"#ref-35\",\"children\":\"35 36\"}],\" Second, we only detected cognitive impairment 4 weeks’ postoperation, which might not sufficiently estimate the impact of CCH on cognitive function since the emergence of cognitive impairment was a chronic process in real VCI patients. Some studies found that 0.18 mm BCAS mice showed impairment of motor function and spatial reference memory alone with some other pathological changes not shown within short period after 6 months.\",[\"$\",\"a\",\"5\",{\"id\":\"xref-ref-7-3\",\"className\":\"xref-bibr\",\"href\":\"#ref-7\",\"children\":\"7 37\"}],\" Therefore, it is critical to further evaluate the impact of compromise CBF on the neuropathy and cognitive impairment after a longer time postoperation.\"]}],[\"$\",\"p\",\"8\",{\"id\":\"p-38\",\"children\":\"In conclusion, our study provided valuable information for scientific researchers to choose 0.16/0.18 mm BCAS as an appropriate mouse model to elucidate the pathophysiology and develop therapeutic strategy for VCI in human.\"}]]}],[\"$\",\"$L26\",null,{\"targetId\":\"article-title-1\"}]]}],[\"$\",\"$1e\",\"9\",{}],[\"$\",\"$1e\",\"10\",{}],[\"$\",\"$1e\",\"11\",{}],[\"$\",\"section\",\"12\",{\"className\":\"article-body-sections order-2 mb-0\",\"children\":[\"$\",\"section\",null,{\"id\":\"fn-group-1\",\"className\":\"!mt-0\",\"children\":[\"$\",\"$L2b\",null,{\"ids\":[\"fn-group-1\"],\"title\":\"Footnotes\",\"children\":[\"$\",\"div\",null,{\"data-testid\":\"article-footnotes\",\"children\":[\"$\",\"div\",null,{\"data-testid\":\"footnotes\",\"children\":[[\"$\",\"div\",null,{\"className\":\"[\u0026_p]:text-bmj-silver-800 list-none[\u0026_ul]:m-0 m-0 [\u0026_ul]:list-none [\u0026_ul]:p-0\",\"data-testid\":\"footnotes-contents\",\"children\":[[\"$\",\"div\",null,{\"dangerouslySetInnerHTML\":{\"__html\":\"$2c\"}}],[\"$\",\"div\",null,{\"data-testid\":\"DEA-section\",\"className\":\"text-bmj-silver-800 p-0\",\"children\":[[\"$\",\"div\",null,{\"className\":\"wrap-urls my-6\",\"children\":[[\"$\",\"p\",null,{\"data-testid\":\"data-availability-title\",\"className\":\"m-0 mb-4 text-base font-bold \",\"children\":\"Data availability statement\"}],[\"$\",\"section\",null,{\"data-testid\":\"data-availability-text\",\"className\":\"m-0\",\"dangerouslySetInnerHTML\":{\"__html\":\"\u003chtml\u003e\u003chead\u003e\u003c/head\u003e\u003cbody\u003e\u003cdiv class=\\\"section data-availability\\\" id=\\\"sec-29\\\"\u003e\u003cp id=\\\"p-45\\\"\u003eData are available in a public, open access repository.\u003c/p\u003e\u003c/div\u003e\u003c/body\u003e\u003c/html\u003e\"}}]]}],[\"$\",\"div\",null,{\"className\":\"wrap-urls mb-6\",\"children\":[[\"$\",\"p\",null,{\"data-testid\":\"ethics-title\",\"className\":\"mb-4 text-base font-bold\",\"children\":\"Ethics statements\"}],[\"$\",\"section\",null,{\"className\":\"m-0 mt-2\",\"children\":[[\"$\",\"section\",null,{\"data-testid\":\"ethics-consent-section\",\"className\":\"mb-[16px]\",\"children\":[\"Patient consent for publication: \",[\"$\",\"span\",null,{\"data-testid\":\"ethics-consent-text\",\"className\":\"font-bold\",\"dangerouslySetInnerHTML\":{\"__html\":\"\u003cp id=\\\"p-46\\\" class=\\\"ethics-consent-to-publish\\\"\u003eNot applicable.\u003c/p\u003e\"}}]]}],[\"$\",\"section\",null,{\"data-testid\":\"ethics-approval-section\",\"className\":\"m-0\",\"children\":[\"Ethics approval: \",[\"$\",\"span\",null,{\"data-testid\":\"ethics-approval-text\",\"className\":\"m-0 font-bold\",\"dangerouslySetInnerHTML\":{\"__html\":\"\u003cp id=\\\"p-47\\\" class=\\\"ethics-approval\\\"\u003eAll animal experiment procedures were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC), Fudan University, Shanghai, China.\u003c/p\u003e\"}}]]}]]}]]}],[\"$\",\"div\",null,{\"className\":\"wrap-urls mb-6\",\"children\":[[\"$\",\"p\",null,{\"data-testid\":\"acknowledgements-title\",\"className\":\"m-0 mb-4 text-base font-bold\",\"children\":\"Acknowledgements\"}],[\"$\",\"section\",null,{\"data-testid\":\"acknowledgements-text\",\"className\":\"[\u0026_a]:text-bmj-blue-600 [\u0026_a]:hover:text-bmj-blue-700 [\u0026_a]:active:text-bmj-blue-800 [\u0026_a]:focus:text-bmj-silver-800 [\u0026_a]:focus-visible:border-bmj-silver-500 m-0 [\u0026_a]:outline-none [\u0026_a]:focus-visible:rounded-md [\u0026_a]:focus-visible:border-[1px]\",\"dangerouslySetInnerHTML\":{\"__html\":\"\u003chtml\u003e\u003chead\u003e\u003c/head\u003e\u003cbody\u003e\u003cdiv class=\\\"section ack\\\" id=\\\"ack-1\\\"\u003e\u003cp id=\\\"p-39\\\"\u003eWe are especially thankful to all the members of Yang Lab, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University for the aid they offered in this study.\u003c/p\u003e\u003c/div\u003e\u003c/body\u003e\u003c/html\u003e\"}}]]}]]}]]}],[\"$\",\"$L26\",null,{\"targetId\":\"article-title-1\"}]]}]}]}]}]}],[\"$\",\"$1e\",\"13\",{}],[\"$\",\"section\",\"14\",{\"className\":\"section ref-list order-1\",\"id\":\"ref-list-1\",\"children\":[\"$\",\"section\",null,{\"data-testid\":\"reference-list\",\"id\":\"ref-list-1\",\"children\":[\"$\",\"$L2b\",null,{\"title\":\"References\",\"ids\":[\"ref-1\",\"ref-2\",\"ref-3\",\"ref-4\",\"ref-5\",\"ref-6\",\"ref-7\",\"ref-8\",\"ref-9\",\"ref-10\",\"ref-11\",\"ref-12\",\"ref-13\",\"ref-14\",\"ref-15\",\"ref-16\",\"ref-17\",\"ref-18\",\"ref-19\",\"ref-20\",\"ref-21\",\"ref-22\",\"ref-23\",\"ref-24\",\"ref-25\",\"ref-26\",\"ref-27\",\"ref-28\",\"ref-29\",\"ref-30\",\"ref-31\",\"ref-32\",\"ref-33\",\"ref-34\",\"ref-35\",\"ref-36\",\"ref-37\",\"ref-list-1\"],\"children\":[[\"$\",\"ol\",null,{\"className\":\"m-0 list-decimal\",\"data-testid\":\"reference-list-ol\",\"children\":[[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-1\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-1\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-1-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"van der Flier WM\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Skoog I\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Schneider JA\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Vascular cognitive impairment. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Nat Rev Dis Primers\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2018\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"4\",\":\",\"18003\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1038/nrdp.2018.3\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1038/nrdp.2018.3\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Vascular cognitive impairment\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/29446769/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-2\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-2\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-1-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Skrobot OA\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Attems J\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Esiri M\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Brain\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2016\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"139\",\":\",\"2957–69\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1093/brain/aww214\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1093/brain/aww214\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Vascular cognitive impairment neuropathology guidelines (VCING): the contribution of cerebrovascular pathology to cognitive impairment\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/27591113/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-3\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-3\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-3-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Román GC\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Tatemichi TK\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Erkinjuntti T\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Neurology\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"1993\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"43\",\":\",\"250–60\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1212/WNL.43.2.250\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1212/WNL.43.2.250\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/8094895/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-4\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-4\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-3-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Kalaria RN\",\". \"]}]],false],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"The pathology and pathophysiology of vascular dementia. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Neuropharmacology\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2018\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"134\",\":\",\"226–39\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/j.neuropharm.2017.12.030\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/j.neuropharm.2017.12.030\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=The pathology and pathophysiology of vascular dementia\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/29273521/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-5\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-5\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-5-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Iadecola C\",\". \"]}]],false],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"The pathobiology of vascular dementia. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Neuron\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2013\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"80\",\":\",\"844–66\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/j.neuron.2013.10.008\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/j.neuron.2013.10.008\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=The pathobiology of vascular dementia\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/24267647/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-6\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-6\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-5-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Snyder HM\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Corriveau RA\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Craft S\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Vascular contributions to cognitive impairment and dementia including Alzheimer's disease. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Alzheimers Dement\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2015\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"11\",\":\",\"710–7\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/j.jalz.2014.10.008\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/j.jalz.2014.10.008\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Vascular contributions to cognitive impairment and dementia including Alzheimer's disease\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/25510382/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-7\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-7\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-7-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Yang Y\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Kimura-Ohba S\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Thompson J\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Rodent models of vascular cognitive impairment. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Transl Stroke Res\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2016\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"7\",\":\",\"407–14\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1007/s12975-016-0486-2\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1007/s12975-016-0486-2\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Rodent models of vascular cognitive impairment\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/27498679/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-8\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-8\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-7-2\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Tuo Q-zhang\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Zou J-jun\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Lei P\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Rodent models of vascular cognitive impairment. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"J Mol Neurosci\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2021\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"71\",\":\",\"1–12\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1007/s12031-020-01733-2\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1007/s12031-020-01733-2\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Rodent models of vascular cognitive impairment\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],null]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-9\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-9\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-9-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Madigan JB\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Wilcock DM\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Hainsworth AH\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Vascular contributions to cognitive impairment and dementia: topical review of animal models. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Stroke\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2016\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"47\",\":\",\"1953–9\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1161/STROKEAHA.116.012066\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1161/STROKEAHA.116.012066\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Vascular contributions to cognitive impairment and dementia: topical review of animal models\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/27301939/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-10\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-10\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-10-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Duncombe J\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Kitamura A\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Hase Y\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. closing the translational gap between rodent models and human vascular cognitive impairment and dementia. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Clin Sci\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2017\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"131\",\":\",\"2451–68\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1042/CS20160727\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1042/CS20160727\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. closing the translational gap between rodent models and human vascular cognitive impairment and dementia\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/28963120/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-11\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-11\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-11-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Barone FC\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Knudsen DJ\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Nelson AH\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Mouse strain differences in susceptibility to cerebral ischemia are related to cerebral vascular anatomy. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"J Cereb Blood Flow Metab\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"1993\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"13\",\":\",\"683–92\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1038/jcbfm.1993.87\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1038/jcbfm.1993.87\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Mouse strain differences in susceptibility to cerebral ischemia are related to cerebral vascular anatomy\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/8314921/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-12\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-12\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-12-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Song Y\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Li Z\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"He T\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Theranostics\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2019\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"9\",\":\",\"2910–23\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.7150/thno.30879\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.7150/thno.30879\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/31244932/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-13\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-13\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-13-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Wang J\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Lin X\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Mu Z\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Rapamycin increases collateral circulation in rodent brain after focal ischemia as detected by multiple modality dynamic imaging. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Theranostics\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2019\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"9\",\":\",\"4923–34\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.7150/thno.32676\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.7150/thno.32676\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Rapamycin increases collateral circulation in rodent brain after focal ischemia as detected by multiple modality dynamic imaging\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/31410191/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-14\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-14\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-14-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Vorhees CV\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Williams MT\",\". \"]}]],false],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Morris water maze: procedures for assessing spatial and related forms of learning and memory. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Nat Protoc\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2006\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"1\",\":\",\"848–58\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1038/nprot.2006.116\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1038/nprot.2006.116\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Morris water maze: procedures for assessing spatial and related forms of learning and memory\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/17406317/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-15\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-15\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-9-2\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Hodges H\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Nelson A\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Virley D\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Cognitive deficits induced by global cerebral ischaemia: prospects for transplant therapy. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Pharmacol Biochem Behav\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"1997\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"56\",\":\",\"763–80\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/S0091-3057(96)00424-8\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/S0091-3057(96)00424-8\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Cognitive deficits induced by global cerebral ischaemia: prospects for transplant therapy\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/9130304/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-16\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-16\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-16-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"León-Moreno LC\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Castañeda-Arellano R\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Rivas-Carrillo JD\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Challenges and improvements of developing an ischemia mouse model through bilateral common carotid artery occlusion. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"J Stroke Cerebrovasc Dis\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2020\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"29\",\":\",\"104773\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2020.104773\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/j.jstrokecerebrovasdis.2020.104773\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Challenges and improvements of developing an ischemia mouse model through bilateral common carotid artery occlusion\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/32199775/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-17\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-17\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-5-2\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Min L-J\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Iwanami J\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Shudou M\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Deterioration of cognitive function after transient cerebral ischemia with amyloid-β infusion-possible amelioration of cognitive function by AT2 receptor activation. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"J Neuroinflammation\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2020\",\"; \"]}],\"17\",\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1186/s12974-020-01775-8\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1186/s12974-020-01775-8\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Deterioration of cognitive function after transient cerebral ischemia with amyloid-β infusion-possible amelioration of cognitive function by AT2 receptor activation\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/32264971/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-18\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-18\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-5-2\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Li W\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Huang R\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Shetty RA\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Neurobiol Dis\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2013\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"59\",\":\",\"18–25\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/j.nbd.2013.06.014\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/j.nbd.2013.06.014\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Transient focal cerebral ischemia induces long-term cognitive function deficit in an experimental ischemic stroke model\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/23845275/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-19\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-19\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-19-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Hermawati E\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Arfian N\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Partadiredja G\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Spatial memory disturbance following transient brain ischemia is associated with vascular remodeling in hippocampus. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Kobe J Med Sci\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2018\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"64\",\":\",\"E93–106\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[null,[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Spatial memory disturbance following transient brain ischemia is associated with vascular remodeling in hippocampus\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/30666039/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-20\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-20\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-20-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Beason-Held LL\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Moghekar A\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Zonderman AB\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Longitudinal changes in cerebral blood flow in the older hypertensive brain. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Stroke\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2007\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"38\",\":\",\"1766–73\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1161/STROKEAHA.106.477109\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1161/STROKEAHA.106.477109\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Longitudinal changes in cerebral blood flow in the older hypertensive brain\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/17510458/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-21\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-21\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-21-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Yoshizaki K\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Adachi K\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Kataoka S\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Exp Neurol\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2008\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"210\",\":\",\"585–91\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/j.expneurol.2007.12.005\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/j.expneurol.2007.12.005\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Chronic cerebral hypoperfusion induced by right unilateral common carotid artery occlusion causes delayed white matter lesions and cognitive impairment in adult mice\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/18222425/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-22\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-22\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-22-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Chai X\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Li X\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Zhang W\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Legumain knockout improved cognitive impairment via reducing neuroinflammation in right unilateral common carotid artery occlusion mice. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Life Sci\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2021\",\"; \"]}],\"285\",\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/j.lfs.2021.119944\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/j.lfs.2021.119944\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Legumain knockout improved cognitive impairment via reducing neuroinflammation in right unilateral common carotid artery occlusion mice\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/34509465/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-23\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-23\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-22-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Zhou Y\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Zhang J\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Wang L\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Interleukin-1β impedes oligodendrocyte progenitor cell recruitment and white matter repair following chronic cerebral hypoperfusion. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Brain Behav Immun\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2017\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"60\",\":\",\"93–105\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/j.bbi.2016.09.024\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/j.bbi.2016.09.024\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Interleukin-1β impedes oligodendrocyte progenitor cell recruitment and white matter repair following chronic cerebral hypoperfusion\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/27663285/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-24\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-24\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-24-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Shibata M\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Ohtani R\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Ihara M\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Stroke\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2004\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"35\",\":\",\"2598–603\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1161/01.STR.0000143725.19053.60\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1161/01.STR.0000143725.19053.60\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=White matter lesions and glial activation in a novel mouse model of chronic cerebral hypoperfusion\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/15472111/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-25\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-25\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-25-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Bink DI\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Ritz K\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Aronica E\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"J Cereb Blood Flow Metab\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2013\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"33\",\":\",\"1666–84\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1038/jcbfm.2013.140\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1038/jcbfm.2013.140\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Mouse models to study the effect of cardiovascular risk factors on brain structure and cognition\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/23963364/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-26\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-26\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-25-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Poh L\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Fann DY\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Wong P\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Aim2 inflammasome mediates hallmark neuropathological alterations and cognitive impairment in a mouse model of vascular dementia. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Mol Psychiatry\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2021\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"26\",\":\",\"4544–60\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1038/s41380-020-00971-5\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1038/s41380-020-00971-5\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Aim2 inflammasome mediates hallmark neuropathological alterations and cognitive impairment in a mouse model of vascular dementia\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/33299135/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-27\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-27\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-27-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Nishio K\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Ihara M\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Yamasaki N\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"A mouse model characterizing features of vascular dementia with hippocampal atrophy. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Stroke\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2010\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"41\",\":\",\"1278–84\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1161/STROKEAHA.110.581686\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1161/STROKEAHA.110.581686\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=A mouse model characterizing features of vascular dementia with hippocampal atrophy\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/20448204/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-28\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-28\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-27-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Ihara M\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Tomimoto H\",\". \"]}]],false],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Lessons from a mouse model characterizing features of vascular cognitive impairment with white matter changes. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"J Aging Res\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2011\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"2011\",\":\",\"1–11\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.4061/2011/978761\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.4061/2011/978761\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Lessons from a mouse model characterizing features of vascular cognitive impairment with white matter changes\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/22132331/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-29\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-29\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-24-3\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"An L\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Chopp M\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Zacharek A\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Cardiac dysfunction in a mouse vascular dementia model of bilateral common carotid artery stenosis. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Front Cardiovasc Med\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2021\",\"; \"]}],\"8\",\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.3389/fcvm.2021.681572\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.3389/fcvm.2021.681572\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Cardiac dysfunction in a mouse vascular dementia model of bilateral common carotid artery stenosis\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],null]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-30\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-30\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-24-3\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Liu Q\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Shkirkova K\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Lamorie-Foote K\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Air pollution particulate matter exposure and chronic cerebral hypoperfusion and measures of white matter injury in a murine model. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Environ Health Perspect\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2021\",\"; \"]}],\"129\",\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1289/EHP8792\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1289/EHP8792\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Air pollution particulate matter exposure and chronic cerebral hypoperfusion and measures of white matter injury in a murine model\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/34424052/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-31\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-31\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-24-3\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Xie Y\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Zhang X\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Xu P\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Aberrant oligodendroglial LDL receptor orchestrates demyelination in chronic cerebral ischemia. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"J Clin Invest\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2021\",\"; \"]}],\"131\",\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1172/JCI128114\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1172/JCI128114\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Aberrant oligodendroglial LDL receptor orchestrates demyelination in chronic cerebral ischemia\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/33141760/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-32\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-32\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-32-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Chen Z\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Venkat P\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Seyfried D\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Brain-Heart interaction: cardiac complications after stroke. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Circ Res\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2017\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"121\",\":\",\"451–68\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1161/CIRCRESAHA.117.311170\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1161/CIRCRESAHA.117.311170\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Brain-Heart interaction: cardiac complications after stroke\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/28775014/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-33\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-33\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-20-2\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Gorelick PB\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Counts SE\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Nyenhuis D\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Vascular cognitive impairment and dementia. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Biochim Biophys Acta\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2016\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"1862\",\":\",\"860–8\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/j.bbadis.2015.12.015\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/j.bbadis.2015.12.015\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Vascular cognitive impairment and dementia\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/26704177/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-34\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-34\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-34-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Kapadia M\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Xu J\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Sakic B\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"The water maze paradigm in experimental studies of chronic cognitive disorders: theory, protocols, analysis, and inference. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Neurosci Biobehav Rev\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2016\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"68\",\":\",\"195–217\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/j.neubiorev.2016.05.016\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/j.neubiorev.2016.05.016\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=The water maze paradigm in experimental studies of chronic cognitive disorders: theory, protocols, analysis, and inference\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/27229758/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-35\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-35\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-35-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Tucker LB\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Velosky AG\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"McCabe JT\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Applications of the Morris water maze in translational traumatic brain injury research. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Neurosci Biobehav Rev\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2018\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"88\",\":\",\"187–200\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/j.neubiorev.2018.03.010\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/j.neubiorev.2018.03.010\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Applications of the Morris water maze in translational traumatic brain injury research\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/29545166/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-36\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-36\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-35-1\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Conrad CD\",\". \"]}]],false],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"A critical review of chronic stress effects on spatial learning and memory. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"Prog Neuropsychopharmacol Biol Psychiatry\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2010\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"34\",\":\",\"742–55\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1016/j.pnpbp.2009.11.003\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1016/j.pnpbp.2009.11.003\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=A critical review of chronic stress effects on spatial learning and memory\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/19903505/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}],[\"$\",\"li\",null,{\"data-testid\":\"reference-item-ref-37\",\"children\":[\"$\",\"div\",null,{\"className\":\"my-4 flex items-center\",\"id\":\"ref-37\",\"children\":[\"$\",\"section\",null,{\"className\":\"relative pl-[25px] leading-[24px]\",\"children\":[[\"$\",\"span\",null,{\"className\":\"absolute left-0 h-100\",\"children\":[[\"$\",\"a\",null,{\"href\":\"#xref-ref-7-3\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 mr-[1px]\",\"data-testid\":\"reference-link\",\"children\":[\"$\",\"img\",null,{\"src\":\"/next-resources/circle-arrow-up.svg\",\"alt\":\"close\",\"className\":\"inline h-4 mt-1\",\"data-testid\":\"citation-arrow-img\"}]}],\" \"]}],[[[\"$\",\"span\",\"0\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-0\",\"children\":[\"Tuo Q-Z\",\", \"]}],[\"$\",\"span\",\"1\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-1\",\"children\":[\"Zou J-J\",\", \"]}],[\"$\",\"span\",\"2\",{\"className\":\"text-bmj-silver-800\",\"data-testid\":\"author-2\",\"children\":[\"Lei P\",\", \"]}]],[\"$\",\"span\",null,{\"data-testid\":\"authors-etal\",\"className\":\"text-bmj-silver-800\",\"children\":\"et al. \"}]],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800 wrap-urls\",\"data-testid\":\"reference-title\",\"dangerouslySetInnerHTML\":{\"__html\":\"Rodent models of vascular cognitive impairment. \"}}],[\"$\",\"span\",null,{\"className\":\"text-bmj-silver-800\",\"children\":[[[\"$\",\"$1e\",\"0\",{\"children\":[[\"$\",\"span\",null,{\"children\":\"J Mol Neurosci\"}],false]}]],\" \",[\"$\",\"span\",null,{\"children\":[\"2021\",\"; \"]}],[\"$\",\"span\",null,{\"children\":[\"71\",\":\",\"1–12\"]}],\". \"]}],[\"$\",\"div\",null,{\"className\":\"inline\",\"data-testid\":\"available-link-container\",\"children\":[null,\"\"]}],[[\"$\",\"a\",null,{\"href\":\"http://dx.doi.org/10.1007/s12031-020-01733-2\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 wrap-urls table-cell\",\"data-testid\":\"link-doi\",\"children\":[\"doi:10.1007/s12031-020-01733-2\",[\"$\",\"span\",null,{\"className\":\"link-separator-dot text-bmj-bg-separator ml-[6px] mr-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}]]}],[\"$\",\"a\",null,{\"href\":\"https://scholar.google.com/scholar?q=Rodent models of vascular cognitive impairment\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-google-scholar\",\"children\":\"Google Scholar\"}],[\"$\",\"a\",null,{\"href\":\"https://pubmed.ncbi.nlm.nih.gov/33107013/\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell\",\"data-testid\":\"link-pubmed\",\"children\":[[\"$\",\"span\",null,{\"className\":\"link-separator-dot separator-dot mr-[6px] ml-[6px] -mt-[1.8px] inline-table h-[20px] w-[4px] align-middle text-[8px]\",\"children\":\"•\"}],\"PubMed\"]}]]]}]}]}]]}],[\"$\",\"$L26\",null,{\"targetId\":\"article-title-1\"}]]}]}]}]]}],[\"$\",\"section\",null,{\"className\":\"mt-6\",\"id\":\"history-list\",\"children\":[\"$\",\"$L2b\",null,{\"ids\":[\"history-list\"],\"title\":\"Publication history\",\"children\":[[\"$\",\"section\",null,{\"aria-labelledby\":\"publication-history-heading\",\"data-testid\":\"publication-history\",\"children\":[[\"$\",\"ul\",null,{\"className\":\"text-bmj-silver-800 m-0 mb-2 list-none p-0\",\"children\":[[\"$\",\"li\",null,{\"className\":\"m-0 p-0 pb-0.5\",\"data-testid\":\"date-entry-received\",\"children\":[\"Received\",\": \",[\"$\",\"strong\",null,{\"children\":\"4 April 2022\"}]]}],[\"$\",\"li\",null,{\"className\":\"m-0 p-0 pb-0.5\",\"data-testid\":\"date-entry-accepted\",\"children\":[\"Accepted\",\": \",[\"$\",\"strong\",null,{\"children\":\"11 May 2022\"}]]}],[\"$\",\"li\",null,{\"className\":\"m-0 p-0 pb-0.5\",\"data-testid\":\"date-entry-first published\",\"children\":[\"First Published\",\": \",[\"$\",\"strong\",null,{\"children\":\"20 December 2022\"}]]}]]}],[\"$\",\"div\",null,{\"data-testid\":\"links-container\",\"children\":[\"\",\"\",\"\"]}]]}],[[\"$\",\"h3\",null,{\"className\":\"m-0 p-0\",\"children\":\"Article Versions\"}],[\"$\",\"ul\",null,{\"className\":\"m-0 p-0\",\"children\":[[\"$\",\"li\",\"Earlier version\",{\"className\":\"m-0 list-none p-0\",\"children\":[\"$\",\"a\",null,{\"href\":\"/content/early/2022/07/11/svn-2022-001594\",\"rel\":\"noopener noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell underline hover:decoration-2 hover:underline-offset-2\",\"children\":[\"Earlier version\",\" - \",\"11 July 2022\"]}]}],[\"$\",\"li\",\"Earlier version\",{\"className\":\"m-0 list-none p-0\",\"children\":[\"$\",\"a\",null,{\"href\":\"/content/early/2022/07/13/svn-2022-001594\",\"rel\":\"noopener noreferrer\",\"className\":\"visible-link text-bmj-blue-600 hover:text-bmj-blue-700 table-cell underline hover:decoration-2 hover:underline-offset-2\",\"children\":[\"Earlier version\",\" - \",\"14 July 2022\"]}]}],[\"$\",\"li\",\"You are viewing the most recent version of this article\",{\"className\":\"m-0 list-none p-0\",\"children\":[\"You are viewing the most recent version of this article\",\" - \",\"20 December 2022\"]}]]}]],[\"$\",\"$L26\",null,{\"targetId\":\"article-title-1\"}]]}]}],[\"$\",\"section\",null,{\"id\":\"rapid-responses\",\"className\":\"article mt-6\",\"children\":[\"$\",\"$L2b\",null,{\"ids\":[\"rapid-responses\"],\"title\":\"Rapid Responses\",\"isLast\":true,\"children\":[[\"$\",\"div\",null,{\"data-testid\":\"compose-rapid-response\",\"className\":\"mb-6\",\"children\":[\"$\",\"a\",null,{\"href\":\"/content/7/6/527/rapid-responses\",\"target\":\"_blank\",\"rel\":\"noreferrer\",\"className\":\"text-bmj-blue-600 focus:text-bmj-blue-800 hover:text-bmj-blue-700 font-bold !no-underline\",\"children\":[\"$\",\"span\",null,{\"className\":\"flex items-center\",\"children\":[\"Compose a Response to This Article\",[\"$\",\"$L2d\",null,{\"className\":\"ml-1 mb-[2px]\"}]]}]}]}],[\"$\",\"$L2e\",null,{\"articlePath\":\"7/6/527\"}],[\"$\",\"$L26\",null,{\"targetId\":\"article-title-1\"}]]}]}],\"\"]}]}],[\"$\",\"div\",null,{\"className\":\"SidebarBox border-bmj-silver-50 col-span-2 overflow-y-auto border-t pr-4 lg:sticky lg:top-[45px] lg:col-span-1 lg:h-screen lg:border-none lg:pl-2 lg:pt-4\",\"children\":[[\"$\",\"div\",null,{\"data-testid\":\"overview\",\"className\":\"wrap-urls mt-0 hidden pb-4 lg:my-6 lg:block\",\"children\":[[\"$\",\"p\",null,{\"data-testid\":\"overview-title\",\"className\":\"text-bmj-silver-800 m-0 mb-4 pt-6 text-xl font-bold lg:pt-0\",\"children\":\"Overview\"}],[\"$\",\"ul\",null,{\"className\":\"m-0 list-none p-0\",\"data-testid\":\"overview-list\",\"children\":[[[\"$\",\"li\",\"abstract-10\",{\"className\":\"mx-0 pl-0 hidden lg:block\",\"children\":[\"$\",\"a\",null,{\"href\":\"#abstract-1\",\"className\":\"text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline\",\"data-testid\":\"overview-list-1\",\"children\":\"Abstract\"}]}],false],[[\"$\",\"li\",\"sec-81\",{\"className\":\"mx-0 pl-0 hidden lg:block\",\"children\":[\"$\",\"a\",null,{\"href\":\"#sec-8\",\"className\":\"text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline\",\"data-testid\":\"overview-list-2\",\"children\":\"Introduction\"}]}],false],[[\"$\",\"li\",\"sec-92\",{\"className\":\"mx-0 pl-0 hidden lg:block\",\"children\":[\"$\",\"a\",null,{\"href\":\"#sec-9\",\"className\":\"text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline\",\"data-testid\":\"overview-list-3\",\"children\":\"Materials and methods\"}]}],false],[[\"$\",\"li\",\"sec-213\",{\"className\":\"mx-0 pl-0 hidden lg:block\",\"children\":[\"$\",\"a\",null,{\"href\":\"#sec-21\",\"className\":\"text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline\",\"data-testid\":\"overview-list-4\",\"children\":\"Results\"}]}],false],[[\"$\",\"li\",\"sec-284\",{\"className\":\"mx-0 pl-0 hidden lg:block\",\"children\":[\"$\",\"a\",null,{\"href\":\"#sec-28\",\"className\":\"text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline\",\"data-testid\":\"overview-list-5\",\"children\":\"Discussion\"}]}],false],[[\"$\",\"li\",\"ref-list-15\",{\"className\":\"mx-0 pl-0 hidden lg:block\",\"children\":[\"$\",\"a\",null,{\"href\":\"#ref-list-1\",\"className\":\"text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline\",\"data-testid\":\"overview-list-6\",\"children\":\"References\"}]}],[\"$\",\"div\",null,{\"data-testid\":\"overview-divider\",\"className\":\"my-6 w-[50%] border border-[#c6c6c9]\"}]],[[\"$\",\"li\",\"fn-group-16\",{\"className\":\"mx-0 pl-0 hidden lg:block\",\"children\":[\"$\",\"a\",null,{\"href\":\"#fn-group-1\",\"className\":\"text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline\",\"data-testid\":\"overview-list-7\",\"children\":\"Footnotes\"}]}],false],[[\"$\",\"li\",\"history-list7\",{\"className\":\"mx-0 pl-0 hidden lg:block\",\"children\":[\"$\",\"a\",null,{\"href\":\"#history-list\",\"className\":\"text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline\",\"data-testid\":\"overview-list-8\",\"children\":\"Publication history\"}]}],false],[[\"$\",\"li\",\"rapid-responses8\",{\"className\":\"mx-0 pl-0 hidden lg:block\",\"children\":[\"$\",\"a\",null,{\"href\":\"#rapid-responses\",\"className\":\"text-bmj-blue-600 hover:text-bmj-blue-700 active:text-bmj-blue-800 leading-6 no-underline\",\"data-testid\":\"overview-list-9\",\"children\":\"Rapid Responses\"}]}],false]]}]]}],\"$L2f\",[\"$\",\"div\",null,{\"className\":\"undefined flex items-center justify-center py-3 undefined undefined\",\"children\":[\"$\",\"div\",null,{\"id\":\"div-gpt-ad-1686906823508-0\",\"data-testid\":\"middle-ad-slot\",\"className\":\"flex items-center justify-center w-[300px] h-[250px] md:h-[600px]\",\"children\":[\"$\",\"$L12\",null,{\"id\":\"slot-ad-div-gpt-ad-1686906823508-0\",\"children\":\"var googletag=googletag||{cmd:[]};googletag.cmd.push(function() {googletag.display(\\\"div-gpt-ad-1686906823508-0\\\");});\"}]}]}]]}]]}]]}]]}]}]]\n"])</script><script>self.__next_f.push([1,"2f:[\"$\",\"main\",null,{\"className\":\"flex flex-col pt-6 lg:pt-0\",\"data-testid\":\"metrics-container\",\"children\":[[\"$\",\"strong\",null,{\"className\":\"text-bmj-silver-800 mb-4 text-xl\",\"children\":\"Article metrics\"}],[\"$\",\"section\",null,{\"data-testid\":\"altmetric-link-container\",\"className\":\"flex flex-row items-center justify-between\",\"children\":[\"$\",\"a\",null,{\"className\":\"hover:text-bmj-blue-700 text-bmj-blue-600 flex items-center justify-between text-base no-underline\",\"href\":\"https://www.altmetric.com/details.php?citation_id=132174841\",\"target\":\"_blank\",\"rel\":\"noopener noreferrer\",\"data-testid\":\"altmetric-link\",\"children\":[\"Altmetric\",[\"$\",\"img\",null,{\"id\":\"open-url-icon-for-metrics\",\"className\":\"m-0 ml-2 h-[14px] w-[14px] p-0\",\"src\":\"/next-resources/open-url-for-metrics.svg\",\"alt\":\"open-url\",\"data-testid\":\"altmetric-icon\"}]]}]}],[\"$\",\"section\",null,{\"data-testid\":\"dimensions-link-container\",\"className\":\"flex flex-row items-center justify-between pb-[1.5rem]\",\"children\":[\"$\",\"a\",null,{\"className\":\"hover:text-bmj-blue-700 text-bmj-blue-600 flex items-center justify-between text-base no-underline\",\"href\":\"https://badge.dimensions.ai/details/doi/10.1136/svn-2022-001594?domain=10.1136/svn-2022-001594\",\"target\":\"_blank\",\"rel\":\"noopener noreferrer\",\"data-testid\":\"dimensions-link\",\"children\":[\"Dimensions\",[\"$\",\"img\",null,{\"id\":\"open-url-icon-for-metrics\",\"className\":\"m-0 ml-2 h-[14px] w-[14px] p-0\",\"src\":\"/next-resources/open-url-for-metrics.svg\",\"alt\":\"open-url\",\"data-testid\":\"dimensions-icon\"}]]}]}]]}]\n"])</script></body></html>