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(PDF) MMP-2 Increase in White Matter from Hypoperfusion
<!DOCTYPE html> <html > <head> <meta charset="utf-8"> <meta rel="search" type="application/opensearchdescription+xml" href="/open_search.xml" title="Academia.edu"> <meta content="width=device-width, initial-scale=1" name="viewport"> <meta name="google-site-verification" content="bKJMBZA7E43xhDOopFZkssMMkBRjvYERV-NaN4R6mrs"> <meta name="csrf-param" content="authenticity_token" /> <meta name="csrf-token" content="XHeK2oxo65cFm1RqzOu-UXs9WMANfWO1X6l7QrUdSQA21rKmoYLbWkkTWiMuGr7-hvUG2pmgWIG71OS4POtQ4Q" /> <meta name="citation_title" content="Chronic Cerebral Hypoperfusion Induces MMP-2 but Not MMP-9 Expression in the Microglia and Vascular Endothelium of White Matter" /> <meta name="citation_publication_date" content="2001" /> <meta name="citation_journal_title" content="Journal of Cerebral Blood Flow &amp; Metabolism" /> <meta name="citation_author" content="Masafumi Ihara" /> <meta name="citation_author" content="Hidekazu Tomimoto" /> <meta name="citation_author" content="Makoto Kinoshita" /> <meta name="citation_author" content="Junseo Oh" /> <meta name="citation_author" content="Makoto Noda" /> <meta name="citation_author" content="Hideaki Wakita" /> <meta name="citation_author" content="Ichiro Akiguchi" /> <meta name="citation_author" content="Hiroshi Shibasaki" /> <meta name="citation_volume" content="21" /> <meta name="citation_issue" content="7" /> <meta name="citation_firstpage" content="828-834" /> <meta name="citation_issn" content="0271-678X" /> <meta name="twitter:card" content="summary" /> <meta name="twitter:url" content="https://www.academia.edu/104769122/Chronic_Cerebral_Hypoperfusion_Induces_MMP_2_but_Not_MMP_9_Expression_in_the_Microglia_and_Vascular_Endothelium_of_White_Matter" /> <meta name="twitter:title" content="Chronic Cerebral Hypoperfusion Induces MMP-2 but Not MMP-9 Expression in the Microglia and Vascular Endothelium of White Matter" /> <meta name="twitter:description" content="White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white" /> <meta name="twitter:image" content="http://a.academia-assets.com/images/twitter-card.jpeg" /> <meta property="fb:app_id" content="2369844204" /> <meta property="og:type" content="article" /> <meta property="og:url" content="https://www.academia.edu/104769122/Chronic_Cerebral_Hypoperfusion_Induces_MMP_2_but_Not_MMP_9_Expression_in_the_Microglia_and_Vascular_Endothelium_of_White_Matter" /> <meta property="og:title" content="Chronic Cerebral Hypoperfusion Induces MMP-2 but Not MMP-9 Expression in the Microglia and Vascular Endothelium of White Matter" /> <meta property="og:image" content="http://a.academia-assets.com/images/open-graph-icons/fb-paper.gif" /> <meta property="og:description" content="White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white" /> <meta property="article:author" content="https://independent.academia.edu/HidekazuTomimoto" /> <meta name="description" content="White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white" /> <title>(PDF) MMP-2 Increase in White Matter from Hypoperfusion</title> <link rel="canonical" href="https://www.academia.edu/104769122/Chronic_Cerebral_Hypoperfusion_Induces_MMP_2_but_Not_MMP_9_Expression_in_the_Microglia_and_Vascular_Endothelium_of_White_Matter" /> <script async src="https://www.googletagmanager.com/gtag/js?id=G-5VKX33P2DS"></script> <script> window.dataLayer = window.dataLayer || []; function gtag(){dataLayer.push(arguments);} gtag('js', new Date()); gtag('config', 'G-5VKX33P2DS', { cookie_domain: 'academia.edu', send_page_view: false, }); gtag('event', 'page_view', { 'controller': "single_work", 'action': "show", 'controller_action': 'single_work#show', 'logged_in': 'false', 'edge': 'unknown', // Send nil if there is no A/B test bucket, in case some records get logged // with missing data - that way we can distinguish between the two cases. // ab_test_bucket should be of the form <ab_test_name>:<bucket> 'ab_test_bucket': null, }) </script> <script> var $controller_name = 'single_work'; var $action_name = "show"; var $rails_env = 'production'; var $app_rev = 'dc2ad41da5d7ea682babd20f90650302fb0a3a36'; var $domain = 'academia.edu'; var $app_host = "academia.edu"; var $asset_host = "academia-assets.com"; var $start_time = new Date().getTime(); var $recaptcha_key = "6LdxlRMTAAAAADnu_zyLhLg0YF9uACwz78shpjJB"; var $recaptcha_invisible_key = "6Lf3KHUUAAAAACggoMpmGJdQDtiyrjVlvGJ6BbAj"; var $disableClientRecordHit = false; </script> <script> window.require = { config: function() { return function() {} } } </script> <script> window.Aedu = window.Aedu || {}; window.Aedu.hit_data = null; window.Aedu.serverRenderTime = new Date(1739804985000); window.Aedu.timeDifference = new Date().getTime() - 1739804985000; </script> <script type="application/ld+json">{"@context":"https://schema.org","@type":"ScholarlyArticle","abstract":"White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white matter in a rat model of chronic cerebral hypoperfusion. After bilateral clipping of the common carotid arteries, myelin staining revealed demyelinating changes in the optic tract and the corpus callosum on day 7. Zymographic analyses indicated an increase in the level of MMP-2, but not MMP-9, after the hypoperfusion. Immunohistochemical analyses revealed the presence (most abundantly on day 3) of MMP-2–expressing activated microglia in the optic tract and corpus callosum. In contrast, the capillary endothelial cells expressed MMP-2 later. IgM-immunoreactive glial cells were absent in the sham-operated animals, but were present in the hypoperfused animals by day 3, reflecting the disrupted blood–brain barrier. These findings suggest tha...","author":[{"@context":"https://schema.org","@type":"Person","name":"Hidekazu Tomimoto","url":"https://independent.academia.edu/HidekazuTomimoto"}],"contributor":[],"dateCreated":"2023-07-20","dateModified":"2025-01-31","datePublished":"2001-01-01","headline":"Chronic Cerebral Hypoperfusion Induces MMP-2 but Not MMP-9 Expression in the Microglia and Vascular Endothelium of White Matter","image":"https://attachments.academia-assets.com/104409592/thumbnails/1.jpg","inLanguage":"en","keywords":["Biology","Immunohistochemistry","Medicine","Gene expression","Brain","Corpus Callosum","Capillaries","Blood brain barrier","Microglia","Glial Cell","Constriction Industry","Clinical Sciences","Cognitive impairment","Endothelial cell","Matrix Metalloproteinase","Constriction","immunoglobulin M","Cardiovascular medicine and haematology"],"publication":"Journal of Cerebral Blood Flow \u0026amp; 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"https://www.academia.edu/login?post_login_redirect_url=https%3A%2F%2Fwww.academia.edu%2F104769122%2FChronic_Cerebral_Hypoperfusion_Induces_MMP_2_but_Not_MMP_9_Expression_in_the_Microglia_and_Vascular_Endothelium_of_White_Matter%3Fshow_translation%3Dtrue"; window.loswp.previewableAttachments = [{"id":104409592,"identifier":"Attachment_104409592","shouldShowBulkDownload":false}]; window.loswp.shouldDetectTimezone = true; window.loswp.shouldShowBulkDownload = true; window.loswp.showSignupCaptcha = false window.loswp.willEdgeCache = false; window.loswp.work = {"work":{"id":104769122,"created_at":"2023-07-20T12:10:41.837-07:00","from_world_paper_id":237658746,"updated_at":"2025-01-31T16:38:53.089-08:00","_data":{"abstract":"White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white matter in a rat model of chronic cerebral hypoperfusion. After bilateral clipping of the common carotid arteries, myelin staining revealed demyelinating changes in the optic tract and the corpus callosum on day 7. Zymographic analyses indicated an increase in the level of MMP-2, but not MMP-9, after the hypoperfusion. Immunohistochemical analyses revealed the presence (most abundantly on day 3) of MMP-2–expressing activated microglia in the optic tract and corpus callosum. In contrast, the capillary endothelial cells expressed MMP-2 later. IgM-immunoreactive glial cells were absent in the sham-operated animals, but were present in the hypoperfused animals by day 3, reflecting the disrupted blood–brain barrier. These findings suggest tha...","publisher":"SAGE Publications","ai_title_tag":"MMP-2 Increase in White Matter from Hypoperfusion","publication_date":"2001,,","publication_name":"Journal of Cerebral Blood Flow \u0026amp; Metabolism"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Chronic Cerebral Hypoperfusion Induces MMP-2 but Not MMP-9 Expression in the Microglia and Vascular Endothelium of White Matter","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [39378877]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "control"; window.loswp.useOptimizedScribd4genScript = false; window.loginModal = {}; window.loginModal.appleClientId = 'edu.academia.applesignon'; window.userInChina = "false";</script><script defer="" src="https://accounts.google.com/gsi/client"></script><div class="ds-loswp-container"><div class="ds-work-card--grid-container"><div class="ds-work-card--container js-loswp-work-card"><div class="ds-work-card--cover"><div class="ds-work-cover--wrapper"><div class="ds-work-cover--container"><button class="ds-work-cover--clickable js-swp-download-button" data-signup-modal="{"location":"swp-splash-paper-cover","attachmentId":104409592,"attachmentType":"pdf"}"><img alt="First page of “Chronic Cerebral Hypoperfusion Induces MMP-2 but Not MMP-9 Expression in the Microglia and Vascular Endothelium of White Matter”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/104409592/mini_magick20230720-1-6uz0b4.png?1689880277" /><img alt="PDF Icon" class="ds-work-cover--file-icon" src="//a.academia-assets.com/images/single_work_splash/adobe_icon.svg" /><div class="ds-work-cover--hover-container"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span><p>Download Free PDF</p></div><div class="ds-work-cover--ribbon-container">Download Free PDF</div><div class="ds-work-cover--ribbon-triangle"></div></button></div></div></div><div class="ds-work-card--work-information"><h1 class="ds-work-card--work-title">Chronic Cerebral Hypoperfusion Induces MMP-2 but Not MMP-9 Expression in the Microglia and Vascular Endothelium of White Matter</h1><div class="ds-work-card--work-authors ds-work-card--detail"><a class="ds-work-card--author js-wsj-grid-card-author ds2-5-body-md ds2-5-body-link" data-author-id="39378877" href="https://independent.academia.edu/HidekazuTomimoto"><img alt="Profile image of Hidekazu Tomimoto" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Hidekazu Tomimoto</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">2001, Journal of Cerebral Blood Flow &amp; Metabolism</p><div class="ds-work-card--work-metadata"><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">visibility</span><p class="ds2-5-body-sm" id="work-metadata-view-count">…</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">description</span><p class="ds2-5-body-sm">7 pages</p></div><div class="ds-work-card--work-metadata__stat"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">link</span><p class="ds2-5-body-sm">1 file</p></div></div><script>(async () => { const workId = 104769122; const worksViewsPath = "/v0/works/views?subdomain_param=api&work_ids%5B%5D=104769122"; const getWorkViews = async (workId) => { const response = await fetch(worksViewsPath); if (!response.ok) { throw new Error('Failed to load work views'); } const data = await response.json(); return data.views[workId]; }; // Get the view count for the work - we send this immediately rather than waiting for // the DOM to load, so it can be available as soon as possible (but without holding up // the backend or other resource requests, because it's a bit expensive and not critical). const viewCount = await getWorkViews(workId); 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} })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">White matter lesions are closely associated with cognitive impairment and motor dysfunction in the aged. To explore the pathophysiology of these lesions, the authors examined the expression of matrix metalloproteinase-2 (MMP-2) and MMP-9 in the white matter in a rat model of chronic cerebral hypoperfusion. After bilateral clipping of the common carotid arteries, myelin staining revealed demyelinating changes in the optic tract and the corpus callosum on day 7. Zymographic analyses indicated an increase in the level of MMP-2, but not MMP-9, after the hypoperfusion. Immunohistochemical analyses revealed the presence (most abundantly on day 3) of MMP-2–expressing activated microglia in the optic tract and corpus callosum. In contrast, the capillary endothelial cells expressed MMP-2 later. IgM-immunoreactive glial cells were absent in the sham-operated animals, but were present in the hypoperfused animals by day 3, reflecting the disrupted blood–brain barrier. These findings suggest tha...</p><div class="ds-work-card--button-container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--work-card","attachmentId":104409592,"attachmentType":"pdf","workUrl":"https://www.academia.edu/104769122/Chronic_Cerebral_Hypoperfusion_Induces_MMP_2_but_Not_MMP_9_Expression_in_the_Microglia_and_Vascular_Endothelium_of_White_Matter"}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--work-card","attachmentId":104409592,"attachmentType":"pdf","workUrl":"https://www.academia.edu/104769122/Chronic_Cerebral_Hypoperfusion_Induces_MMP_2_but_Not_MMP_9_Expression_in_the_Microglia_and_Vascular_Endothelium_of_White_Matter"}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div><div class="ds-signup-banner-trigger-container"><div class="ds-signup-banner-trigger ds-signup-banner-trigger-control"></div></div><div class="ds-signup-banner ds-signup-banner-control"><div id="ds-signup-banner-close-button"><button class="ds2-5-button ds2-5-button--secondary ds2-5-button--inverse"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">close</span></button></div><div class="ds-signup-banner-ctas"><img src="//a.academia-assets.com/images/academia-logo-capital-white.svg" /><h4 class="ds2-5-heading-serif-sm">Sign up for access to the world's latest research</h4><button class="ds2-5-button ds2-5-button--inverse ds2-5-button--full-width js-swp-download-button" data-signup-modal="{"location":"signup-banner"}">Sign up for free<span class="material-symbols-outlined" style="font-size: 20px" translate="no">arrow_forward</span></button></div><div class="ds-signup-banner-divider"></div><div class="ds-signup-banner-reasons"><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Get notified about relevant papers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Save papers to use in your research</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Join the discussion with peers</span></div><div class="ds-signup-banner-reasons-item"><span class="material-symbols-outlined" style="font-size: 24px" translate="no">check</span><span>Track your impact</span></div></div></div><script>(() => { // Set up signup banner show/hide behavior: // 1. 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A disruption of the blood-brain barrier (BBB) is believed to be a critical early event leading to these WM lesions. Previous studies have suggested the involvement of matrix metalloproteinase-2 (MMP-2) in BBB disruptions and the upregulation of MMP-2 after chronic cerebral hypoperfusion in a rat model. In the present study, we asked whether MMP-2 is involved in the BBB disruption and the subsequent WM lesions after chronic cerebral hypoperfusion. Methods-We compared the severity of white matter lesions in rats after chronic cerebral hypoperfusion with or without an MMP inhibitor. Then, we also induced the chronic cerebral hypoperfusion in wild-type and MMP-2-null mice. Results-In the rats treated with a relatively selective MMP-2 inhibitor, AG3340, the WM lesions after chronic cerebral hypoperfusion were significantly less severe, and the number of activated astroglia and microglia were also significantly lower as compared with the vehicle-treated rats. Gene knockout of MMP-2 also reduced the severity of the WM lesions and the number of activated astroglia and microglia in a mice system. In both rodents, the disruption of BBB function, as assessed by IgM staining and the Evans blue extravasation test, was less severe when MMP-2 activity was attenuated.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix metalloproteinase-2 plays a critical role in the pathogenesis of white matter lesions after chronic cerebral hypoperfusion in rodents","attachmentId":45075333,"attachmentType":"pdf","work_url":"https://www.academia.edu/13674419/Matrix_metalloproteinase_2_plays_a_critical_role_in_the_pathogenesis_of_white_matter_lesions_after_chronic_cerebral_hypoperfusion_in_rodents","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/13674419/Matrix_metalloproteinase_2_plays_a_critical_role_in_the_pathogenesis_of_white_matter_lesions_after_chronic_cerebral_hypoperfusion_in_rodents"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="1" data-entity-id="66275287" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/66275287/Chronic_Cerebral_Hypoperfusion_Induces_Alterations_of_Matrix_Metalloproteinase_9_and_Angiopoietin_2_Levels_in_the_Rat_Hippocampus">Chronic Cerebral Hypoperfusion Induces Alterations of Matrix Metalloproteinase-9 and Angiopoietin-2 Levels in the Rat Hippocampus</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="113009636" href="https://independent.academia.edu/JungSooHan1">Jung-Soo Han</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Experimental neurobiology, 2018</p><p class="ds-related-work--abstract ds2-5-body-sm">Angiogenic factors contribute to cerebral angiogenesis following cerebral hypoperfusion, and understanding these temporal changes is essential to developing effective treatments. The present study examined temporal alterations in angiogenesis-related matrix metalloproteinase-9 (MMP-9) and angiopoietin-2 (ANG-2) expression in the hippocampus following bilateral common carotid artery occlusion (BCCAo). Male Wistar rats (12 weeks of age) were randomly assigned to sham-operated control or experimental groups, and expression levels of MMP-9 and ANG-2 were assessed after BCCAo (1 week, 4 weeks, and 8 weeks), using western blotting. Protein expression increased 1 week after BCCAo and returned to control levels at 4 and 8 weeks. In addition, immunofluorescence staining demonstrated that the MMP-9- and ANG-2-positive signals were primarily observed in the NeuN-positive neurons with very little labeling in non-neuronal cells and no labeling in endothelial cells. In addition, these cellular lo...</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Chronic Cerebral Hypoperfusion Induces Alterations of Matrix Metalloproteinase-9 and Angiopoietin-2 Levels in the Rat Hippocampus","attachmentId":77531052,"attachmentType":"pdf","work_url":"https://www.academia.edu/66275287/Chronic_Cerebral_Hypoperfusion_Induces_Alterations_of_Matrix_Metalloproteinase_9_and_Angiopoietin_2_Levels_in_the_Rat_Hippocampus","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/66275287/Chronic_Cerebral_Hypoperfusion_Induces_Alterations_of_Matrix_Metalloproteinase_9_and_Angiopoietin_2_Levels_in_the_Rat_Hippocampus"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="2" data-entity-id="27576927" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/27576927/Microglia_transplantation_attenuates_white_matter_injury_in_rat_chronic_ischemia_model_via_matrix_metalloproteinase_2_inhibition">Microglia transplantation attenuates white matter injury in rat chronic ischemia model via matrix metalloproteinase-2 inhibition</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="51710770" href="https://independent.academia.edu/YamaguchiShuhei">Shuhei Yamaguchi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Brain Research, 2010</p><p class="ds-related-work--abstract ds2-5-body-sm">Chronic cerebral ischemia is thought to induce white matter lesions (WMLs), which contribute to subcortical vascular dementia. Although glial activation and protease upregulation are believed to modify WML pathology, effective therapy remains elusive.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Microglia transplantation attenuates white matter injury in rat chronic ischemia model via matrix metalloproteinase-2 inhibition","attachmentId":47833628,"attachmentType":"pdf","work_url":"https://www.academia.edu/27576927/Microglia_transplantation_attenuates_white_matter_injury_in_rat_chronic_ischemia_model_via_matrix_metalloproteinase_2_inhibition","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/27576927/Microglia_transplantation_attenuates_white_matter_injury_in_rat_chronic_ischemia_model_via_matrix_metalloproteinase_2_inhibition"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="66013420" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/66013420/MMP2_and_MMP9_in_immature_endothelial_cells_following_surgical_injury_of_rat_cerebral_cortex_a_preliminary_study">MMP2 and MMP9 in immature endothelial cells following surgical injury of rat cerebral cortex-a preliminary study</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="38186336" href="https://independent.academia.edu/DorotaSulejczak">Dorota Sulejczak</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Folia …, 2009</p><p class="ds-related-work--abstract ds2-5-body-sm">Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases capable of extracellular matrix remodeling. They have been implicated in various physiological and pathological phenomena involving neurovascular unit elements (neurons, astrocytes and capillary vessels). Surgical injury of the fronto-temporal region of rat cerebral cortex induces massive neurodegeneration and cell death accompanied by astrogliosis. In the area adjacent to the damage, the induction of angiogenesis is observed, in which process immature endothelial cells are important players. The aim of this study was to examine the expression of MMP2 and MMP9 in cortical blood vessels following the surgical injury of cerebral cortex in the rat. Our data demonstrated absence of immature endothelial cells and lack of or only weak MMP2 and MMP9 immunoreactivities in some cortical capillaries in intact rats. Following the surgery, we found high MMPs' immunoreactivities in walls of the vessels located in the cortex adjacent to the lesion site, and particularly in the immature endothelial cells. These results show for the first time the presence of MMPs in the immature (progenitor?) endothelial cells following surgical brain injury.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"MMP2 and MMP9 in immature endothelial cells following surgical injury of rat cerebral cortex-a preliminary study","attachmentId":77368492,"attachmentType":"pdf","work_url":"https://www.academia.edu/66013420/MMP2_and_MMP9_in_immature_endothelial_cells_following_surgical_injury_of_rat_cerebral_cortex_a_preliminary_study","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/66013420/MMP2_and_MMP9_in_immature_endothelial_cells_following_surgical_injury_of_rat_cerebral_cortex_a_preliminary_study"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="4" data-entity-id="33718248" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/33718248/Differential_alterations_in_the_expression_and_activity_of_matrix_metalloproteinases_2_and_9_after_transient_cerebral_ischemia_in_mice">Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="66014727" href="https://independent.academia.edu/SarahGeorge40">Sarah George</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neurobiology of Disease, 2004</p><p class="ds-related-work--abstract ds2-5-body-sm">Abnormal expression and activity of matrix metalloproteinases (MMPs) may contribute to the pathophysiology of cerebral disease such as ischemic injury. In this study, we compared the cellular localization, expression, and activity of MMP-2 and -9 in relation to the evolution of neuronal damage 24 and 72 h after transient global ischemia. In response to ischemia, there was a generalized increase in cellular MMP-2 immunoreactivity at 24-h reperfusion (in neurons, glia and vessels) whereas at 72-h reperfusion the increase in MMP-2 was predominantly in glia. These glial alterations contributed to a significant increase in pro MMP-2 levels in ischemic regions (P b 0.01) as measured by zymography. In contrast, MMP-9 was predominantly upregulated in neurons and this was significantly different to shams at 24-and 72-h reperfusion after ischemia (P b 0.05). Notably, a dramatic increase in proteolytic activity in neurons was observed 24 h after ischemia and this response was absent at 72 h post-ischemia. The present data are supportive of a role for MMPs in contributing to neuronal injury after ischemia. D 2004 Elsevier Inc. All rights reserved.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice","attachmentId":53714994,"attachmentType":"pdf","work_url":"https://www.academia.edu/33718248/Differential_alterations_in_the_expression_and_activity_of_matrix_metalloproteinases_2_and_9_after_transient_cerebral_ischemia_in_mice","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/33718248/Differential_alterations_in_the_expression_and_activity_of_matrix_metalloproteinases_2_and_9_after_transient_cerebral_ischemia_in_mice"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="5" data-entity-id="26745078" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/26745078/Early_reperfusion_injury_is_associated_to_MMP2_and_IL_1%CE%B2_elevation_in_cortical_neurons_of_rats_subjected_to_middle_cerebral_artery_occlusion">Early reperfusion injury is associated to MMP2 and IL-1β elevation in cortical neurons of rats subjected to middle cerebral artery occlusion</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="46811561" href="https://bham.academia.edu/MichelangeloCerto">Dr Michelangelo Certo</a></div><p class="ds-related-work--abstract ds2-5-body-sm">—The pathophysiological processes implicated in ischemic brain damage are strongly affected by an inflam-matory reaction characterized by activation of immune cells and release of soluble mediators, including cytokines and chemokines. The pro-inflammatory cytokine interleukin (IL)-1b has been implicated in ischemic brain injury, however , to date, the mechanisms involved in the maturation of this cytokine in the ischemic brain have not been completely elucidated. We have previously suggested that matrix metalloproteinases (MMPs) may be implicated in cytokine production under pathological conditions. Here, we demonstrate that significant elevation of IL-1b occurs in the cortex as early as 1 h after the beginning of reperfu-sion in rats subjected to 2-h middle cerebral artery occlusion (MCAo). At this early stage, we observe increased expression of IL-1b in pericallosal astroglial cells and in cor-tical neurons and this latter signal colocalizes with elevated gelatinolytic activity. By gel zymography, we demonstrate that the increased gelatinolytic signal at 1-h reperfusion is mainly ascribed to MMP2. Thus, MMP2 seems to contribute to early brain elevation of IL-b after transient ischemia and this mechanism may promote damage since pharmacological inhibition of gelatinases by the selective MMP2/MMP9 inhibitor V provides neuroprotection in rats subjected to transient MCAo.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Early reperfusion injury is associated to MMP2 and IL-1β elevation in cortical neurons of rats subjected to middle cerebral artery occlusion","attachmentId":47024544,"attachmentType":"pdf","work_url":"https://www.academia.edu/26745078/Early_reperfusion_injury_is_associated_to_MMP2_and_IL_1%CE%B2_elevation_in_cortical_neurons_of_rats_subjected_to_middle_cerebral_artery_occlusion","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/26745078/Early_reperfusion_injury_is_associated_to_MMP2_and_IL_1%CE%B2_elevation_in_cortical_neurons_of_rats_subjected_to_middle_cerebral_artery_occlusion"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="6" data-entity-id="45373368" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/45373368/Reduced_brain_edema_and_matrix_metalloproteinase_MMP_expression_by_pre_reperfusion_infusion_into_ischemic_territory_in_rat">Reduced brain edema and matrix metalloproteinase (MMP) expression by pre-reperfusion infusion into ischemic territory in rat</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="42228650" href="https://independent.academia.edu/YuchuanDing">Yuchuan Ding</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neuroscience Letters, 2004</p><p class="ds-related-work--abstract ds2-5-body-sm">The aim in this study was to investigate whether our experimental model for stroke therapy, flushing the ischemic territory with saline prior to reperfusion, could ameliorate disruption of microvascular integrity by reducing matrix metalloproteinase (MMP) expression during reperfusion.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Reduced brain edema and matrix metalloproteinase (MMP) expression by pre-reperfusion infusion into ischemic territory in rat","attachmentId":65901932,"attachmentType":"pdf","work_url":"https://www.academia.edu/45373368/Reduced_brain_edema_and_matrix_metalloproteinase_MMP_expression_by_pre_reperfusion_infusion_into_ischemic_territory_in_rat","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/45373368/Reduced_brain_edema_and_matrix_metalloproteinase_MMP_expression_by_pre_reperfusion_infusion_into_ischemic_territory_in_rat"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="7" data-entity-id="14985235" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/14985235/Matrix_Metalloproteinase_9_Gene_Knock_out_Protects_the_Immature_Brain_after_Cerebral_Hypoxia_Ischemia">Matrix Metalloproteinase-9 Gene Knock-out Protects the Immature Brain after Cerebral Hypoxia-Ischemia</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33981879" href="https://gu-se.academia.edu/CarinaMallard">Carina Mallard</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="34156939" href="https://independent.academia.edu/PernillaSvedin">Pernilla Svedin</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Neuroscience, 2007</p><p class="ds-related-work--abstract ds2-5-body-sm">Inhibition of matrix metalloproteinase-9 (MMP-9) protects the adult brain after cerebral ischemia. However, the role of MMP-9 in the immature brain after hypoxia-ischemia (HI) is unknown. We exposed MMP-9 (Ϫ/Ϫ) [MMP-9 knock-out (KO)] and wild-type (WT) mice to HI on postnatal day 9. HI was induced by unilateral ligation of the left carotid artery followed by hypoxia (10% O 2 ; 36°C). Gelatin zymography showed that MMP-9 activity was transiently increased at 24 h after HI in the ipsilateral hemisphere and MMP-9-positive cells were colocalized with activated microglia. Seven days after 50 min of HI, cerebral tissue volume loss was reduced in MMP-9 KO (21.8 Ϯ 1.7 mm 3 ; n ϭ 22) compared with WT (32.3 Ϯ 2.1 mm 3 ; n ϭ 22; p Ͻ 0.001) pups, and loss of white-matter components was reduced in MMP-9 KO compared with WT pups (neurofilament: WT, 50.9 Ϯ 5.4%; KO, 18.4 Ϯ 3.1%; p Ͻ 0.0001; myelin basic protein: WT, 57.5 Ϯ 5.8%; KO, 23.2 Ϯ 3.5%; p ϭ 0.0001). The neuropathological changes were associated with a delayed and diminished leakage of the blood-brain barrier (BBB) and a decrease in inflammation in MMP-9-deficient animals. In contrast, the neuroprotective effects after HI in MMP-9-deficient animals were not linked to either caspase-dependent (caspase-3 and cytochrome c) or caspase-independent (apoptosis-inducing factor) processes. This study demonstrates that excessive activation of MMP-9 is deleterious to the immature brain, which is associated with the degree of BBB leakage and inflammation. In contrast, apoptosis does not appear to be a major contributing factor.</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix Metalloproteinase-9 Gene Knock-out Protects the Immature Brain after Cerebral Hypoxia-Ischemia","attachmentId":43674386,"attachmentType":"pdf","work_url":"https://www.academia.edu/14985235/Matrix_Metalloproteinase_9_Gene_Knock_out_Protects_the_Immature_Brain_after_Cerebral_Hypoxia_Ischemia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/14985235/Matrix_Metalloproteinase_9_Gene_Knock_out_Protects_the_Immature_Brain_after_Cerebral_Hypoxia_Ischemia"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="8" data-entity-id="17975574" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/17975574/Matrix_Metalloproteinase_Expression_Increases_After_Cerebral_Focal_Ischemia_in_Rats_Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size_Editorial_Comment_Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size">Matrix Metalloproteinase Expression Increases After Cerebral Focal Ischemia in Rats : Inhibition of Matrix Metalloproteinase-9 Reduces Infarct Size Editorial Comment: Inhibition of Matrix Metalloproteinase-9 Reduces Infarct Size</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="37900667" href="https://downstate.academia.edu/FrankBarone">Frank Barone</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Stroke, 1998</p><p class="ds-related-work--abstract ds2-5-body-sm">Background and Purpose-Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade the extracellular matrix and are implicated in numerous pathological conditions including atherosclerosis, inflammation, and tumor growth and metastasis. In the brain, the endothelial cell wall, strengthened by tight junctions, defines the blood-brain barrier (BBB). The extracellular matrix molecules constitute the basement membrane underlying the vasculature and play a critical role in maintaining the integrity of the BBB. After focal stroke, there is a breakdown of the BBB with an associated increase in vascular permeability, inflammatory cell influx, and neuronal cell death. The present study was designed to investigate the effects of MMP expression after stroke. Methods-Focal stroke was produced by permanent middle cerebral artery occlusion (MCAO) in the rat, and MMP protein expression was measured by Western blot and zymogram analysis over a time course ranging from 6 hours to 30 days (nϭ32). Immunohistochemistry at 1 and 5 days (nϭ8 and 6, respectively) was also utilized to characterize the expression of several MMPs and related proteins after stroke, including their cellular source. To test the hypothesis that early increased MMP-9 expression is involved in ischemic brain injury, a neutralizing monoclonal antibody directed against MMP-9 was administered intravenously (nϭ7 per group) 1 hour before MCAO, and infarct size was measured 24 hours later. Results-MMP expression increased progressively over time after stroke. After 12 hours, significant (PϽ0.05) MMP-9 activity was observed that reached maximum levels by 24 hours (PϽ0.001), then persisted for 5 days at this level and returned to basal (zero) levels by 15 days. On the basis of morphological criteria, MMP-9 appeared to stain with endothelial cells and neutrophils identified both within and at the periphery of the infarct within 24 hours of focal ischemia. After 5 days, MMP-9 appeared to stain with macrophages present within the infarcted brain. MMP-2 activity was significantly (PϽ0.001) increased by 24 hours and was maximum after 5 days following MCAO. MMP-2 appeared to stain with macrophages present within the infarcted region. Unlike MMP-9 and MMP-2, tissue inhibitor of metalloproteinase-1 was identified at comparable levels in both control and ischemic tissue after MCAO. MMP-1 and MMP-3 could not be detected in the brain after focal stroke. When an MMP-9 -neutralizing monoclonal antibody was administered systemically, animals exhibited significantly reduced infarct size (ie, a 30% reduction compared with non-immune antibody controls; PϽ0.05). Conclusions-These results demonstrate that early increased MMP-9 expression in endothelial cells and infiltrating neutrophils is a significant response to cerebral focal ischemia and that selective inhibition of MMP-9 activity can significantly reduce brain injury after stroke. (Stroke. 1998;29:1020-1030.)</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix Metalloproteinase Expression Increases After Cerebral Focal Ischemia in Rats : Inhibition of Matrix Metalloproteinase-9 Reduces Infarct Size Editorial Comment: Inhibition of Matrix Metalloproteinase-9 Reduces Infarct Size","attachmentId":39809049,"attachmentType":"pdf","work_url":"https://www.academia.edu/17975574/Matrix_Metalloproteinase_Expression_Increases_After_Cerebral_Focal_Ischemia_in_Rats_Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size_Editorial_Comment_Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/17975574/Matrix_Metalloproteinase_Expression_Increases_After_Cerebral_Focal_Ischemia_in_Rats_Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size_Editorial_Comment_Inhibition_of_Matrix_Metalloproteinase_9_Reduces_Infarct_Size"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-wsj-grid-card" data-collection-position="9" data-entity-id="12993789" data-sort-order="default"><a class="ds-related-work--title js-wsj-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/12993789/Early_upregulation_of_matrix_metalloproteinases_following_reperfusion_triggers_neuroinflammatory_mediators_in_brain_ischemia_in_rat">Early upregulation of matrix metalloproteinases following reperfusion triggers neuroinflammatory mediators in brain ischemia in rat</a><div class="ds-related-work--metadata"><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32207660" href="https://uniromatre.academia.edu/GiorgioBernardi">Giorgio Bernardi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2007</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Early upregulation of matrix metalloproteinases following reperfusion triggers neuroinflammatory mediators in brain ischemia in rat","attachmentId":45793331,"attachmentType":"pdf","work_url":"https://www.academia.edu/12993789/Early_upregulation_of_matrix_metalloproteinases_following_reperfusion_triggers_neuroinflammatory_mediators_in_brain_ischemia_in_rat","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-wsj-grid-card-view-pdf" href="https://www.academia.edu/12993789/Early_upregulation_of_matrix_metalloproteinases_following_reperfusion_triggers_neuroinflammatory_mediators_in_brain_ischemia_in_rat"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div></div></div><div class="ds-sticky-ctas--wrapper js-loswp-sticky-ctas hidden"><div class="ds-sticky-ctas--grid-container"><div class="ds-sticky-ctas--container"><button class="ds2-5-button js-swp-download-button" data-signup-modal="{"location":"continue-reading-button--sticky-ctas","attachmentId":104409592,"attachmentType":"pdf","workUrl":null}">See full PDF</button><button class="ds2-5-button ds2-5-button--secondary js-swp-download-button" data-signup-modal="{"location":"download-pdf-button--sticky-ctas","attachmentId":104409592,"attachmentType":"pdf","workUrl":null}"><span class="material-symbols-outlined" style="font-size: 20px" translate="no">download</span>Download PDF</button></div></div></div><div class="ds-below-fold--grid-container"><div class="ds-work--container js-loswp-embedded-document"><div class="attachment_preview" data-attachment="Attachment_104409592" style="display: none"><div class="js-scribd-document-container"><div class="scribd--document-loading js-scribd-document-loader" style="display: block;"><img alt="Loading..." src="//a.academia-assets.com/images/loaders/paper-load.gif" /><p>Loading Preview</p></div></div><div style="text-align: center;"><div class="scribd--no-preview-alert js-preview-unavailable"><p>Sorry, preview is currently unavailable. You can download the paper by clicking the button above.</p></div></div></div></div><div class="ds-sidebar--container js-work-sidebar"><div class="ds-related-content--container"><h2 class="ds-related-content--heading">Related papers</h2><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="0" data-entity-id="47839462" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/47839462/Matrix_Metalloproteinases_Are_Associated_With_Increased_Blood_Brain_Barrier_Opening_in_Vascular_Cognitive_Impairment">Matrix Metalloproteinases Are Associated With Increased Blood-Brain Barrier Opening in Vascular Cognitive Impairment</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="70559764" href="https://independent.academia.edu/MarkGrossetete">Mark Grossetete</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Stroke, 2011</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix Metalloproteinases Are Associated With Increased Blood-Brain Barrier Opening in Vascular Cognitive Impairment","attachmentId":66756051,"attachmentType":"pdf","work_url":"https://www.academia.edu/47839462/Matrix_Metalloproteinases_Are_Associated_With_Increased_Blood_Brain_Barrier_Opening_in_Vascular_Cognitive_Impairment","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" href="https://www.academia.edu/47839462/Matrix_Metalloproteinases_Are_Associated_With_Increased_Blood_Brain_Barrier_Opening_in_Vascular_Cognitive_Impairment"><span class="ds2-5-text-link__content">View PDF</span><span class="material-symbols-outlined" style="font-size: 18px" translate="no">chevron_right</span></a></div></div><div class="ds-related-work--container js-related-work-sidebar-card" data-collection-position="1" data-entity-id="13451931" data-sort-order="default"><a class="ds-related-work--title js-related-work-grid-card-title ds2-5-body-md ds2-5-body-link" href="https://www.academia.edu/13451931/Increased_Brain_Expression_of_Matrix_Metalloproteinase_9_After_Ischemic_and_Hemorrhagic_Human_Stroke">Increased Brain Expression of Matrix Metalloproteinase-9 After Ischemic and Hemorrhagic Human Stroke</a><div class="ds-related-work--metadata"><a class="js-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="32677912" href="https://independent.academia.edu/CarlosMolina55">Carlos Molina</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Stroke, 2006</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Increased Brain Expression of Matrix Metalloproteinase-9 After Ischemic and Hemorrhagic Human Stroke","attachmentId":45332127,"attachmentType":"pdf","work_url":"https://www.academia.edu/13451931/Increased_Brain_Expression_of_Matrix_Metalloproteinase_9_After_Ischemic_and_Hemorrhagic_Human_Stroke","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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href="https://independent.academia.edu/JoanMontaner1">Joan Montaner</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Cerebral Blood Flow &amp; Metabolism, 2008</p><div class="ds-related-work--ctas"><button class="ds2-5-text-link ds2-5-text-link--inline js-swp-download-button" data-signup-modal="{"location":"wsj-grid-card-download-pdf-modal","work_title":"Matrix Metalloproteinase-13 is Activated and is found in the Nucleus of Neural Cells after Cerebral Ischemia","attachmentId":98275953,"attachmentType":"pdf","work_url":"https://www.academia.edu/96355178/Matrix_Metalloproteinase_13_is_Activated_and_is_found_in_the_Nucleus_of_Neural_Cells_after_Cerebral_Ischemia","alternativeTracking":true}"><span class="material-symbols-outlined" style="font-size: 18px" translate="no">download</span><span class="ds2-5-text-link__content">Download free PDF</span></button><a class="ds2-5-text-link ds2-5-text-link--inline js-related-work-grid-card-view-pdf" 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