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window.loswp.previewableAttachments = [{"id":48596768,"identifier":"Attachment_48596768","shouldShowBulkDownload":false}]; window.loswp.shouldDetectTimezone = true; window.loswp.shouldShowBulkDownload = true; window.loswp.showSignupCaptcha = false window.loswp.willEdgeCache = false; window.loswp.work = {"work":{"id":28271669,"created_at":"2016-09-05T14:57:12.494-07:00","from_world_paper_id":157208483,"updated_at":"2025-01-31T15:12:02.848-08:00","_data":{"ai_title_tag":"Distinct MMP Activity in Brain Development vs. HI","grobid_abstract":"Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases involved in brain development and the etiology of adult cerebral injuries. In this study, we determined the MMP-2 and 9 responses following hypoxic ischemia (HI) injury in the developing brain. First, we characterized the developmental changes of MMP activity in the rat brain from embryonic day 18 (E18) to postnatal day 120 (P120). MMP-2 activity was high from E18 to P3 and decreased with age (P\u003c0.001), while MMP-9 activity was not detectable. MMP-2 immunoreactivity was closely associated with differentiating cortical plate and subplate neurons. Next, we characterized the proteolytic changes after unilateral HI brain injury in 3-(P3) and 21-(P21) day-old rats. Zymography revealed that in the P21 rat brain, MMP-9 activity (150 and 92 kDa forms) was increased at 6 h and remained elevated 24 h post-injury in the ipsilateral injured hemisphere (P\u003c0.001), whereas there was a gradual increase in MMP-2 (65 kDa) activity, reaching a peak at 5 days (P\u003c0.001). Similarly, quantitative real time polymerase chain reaction (qRT-PCR) indicated significant elevations in MMP-9 and MMP-2 mRNA expression in the injured cortex (P\u003c0.05) and hippocampus (P\u003c0.05) at 1 and 5 days post-injury, respectively in the P21 rat brain. In the P3 rat brain, zymography results revealed that both pro (92 kDa) and cleaved (87 kDa) MMP-9 activities were upregulated in the ipsilateral injured hemisphere from 6 h to 1 day after injury (P\u003c0.001). In contrast, cleaved MMP-2 (60 kDa) was only moderately upregulated at 6 h (P\u003c0.01), while pro MMP-2 (65 kDa) levels were unaffected. MMP-9 mRNA expression was also increased at 6 h (P\u003c0.05) following injury at P3, whereas MMP-2 expression remained unchanged compared with the uninjured contralateral hemisphere. Immunohistochemistry indicated that MMP-9 protein expression was localized predominantly to neurons and perivascular astrocytes in the affected regions at early time points, whereas MMP-2 was present on reactive astrocytes surrounding the infarct at later time points. Together, these results indicate that MMP-2 may be primarily associated with the development and differentiation of cortical plate neurons and wound recovery processes. Conversely, MMP-9 appeared to be associated with more acute processes during the period of lesion development.","publication_date":"2009,,","publication_name":"Neuroscience","grobid_abstract_attachment_id":"48596768"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Proteolytic activity during cortical development is distinct from that involved in hypoxic ischemic injury","broadcastable":false,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [52995281]; window.loswp.locale = "en"; window.loswp.countryCode = "SG"; window.loswp.cwvAbTestBucket = ""; window.loswp.designVariant = "ds_vanilla"; window.loswp.fullPageMobileSutdModalVariant = "full_page_mobile_sutd_modal"; 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":48596768,"attachmentType":"pdf"}"><img alt="First page of “Proteolytic activity during cortical development is distinct from that involved in hypoxic ischemic injury”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/48596768/mini_magick20190203-26928-1fe2bm5.png?1549195125" /><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">Proteolytic activity during cortical development is distinct from that involved in hypoxic ischemic injury</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="52995281" href="https://independent.academia.edu/ArjanScheepens"><img alt="Profile image of Arjan Scheepens" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Arjan Scheepens</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">2009, Neuroscience</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">13 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 = 28271669; 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if (!viewCountBody) { throw new Error('Failed to find work views element'); } viewCountBody.textContent = `${commaizedViewCount} views`; } catch (error) { // Remove the whole views element if there was some issue parsing. document.getElementById('work-metadata-view-count')?.parentNode?.remove(); throw new Error(`Failed to parse view count: ${viewCount}`, error); } }; // If the DOM is still loading, wait for it to be ready before updating the view count. if (document.readyState === "loading") { document.addEventListener('DOMContentLoaded', () => { updateViewCount(viewCount); }); // Otherwise, just update it immediately. } else { updateViewCount(viewCount); } })();</script></div><p class="ds-work-card--work-abstract ds-work-card--detail ds2-5-body-md">Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases involved in brain development and the etiology of adult cerebral injuries. In this study, we determined the MMP-2 and 9 responses following hypoxic ischemia (HI) injury in the developing brain. First, we characterized the developmental changes of MMP activity in the rat brain from embryonic day 18 (E18) to postnatal day 120 (P120). MMP-2 activity was high from E18 to P3 and decreased with age (P<0.001), while MMP-9 activity was not detectable. MMP-2 immunoreactivity was closely associated with differentiating cortical plate and subplate neurons. Next, we characterized the proteolytic changes after unilateral HI brain injury in 3-(P3) and 21-(P21) day-old rats. Zymography revealed that in the P21 rat brain, MMP-9 activity (150 and 92 kDa forms) was increased at 6 h and remained elevated 24 h post-injury in the ipsilateral injured hemisphere (P<0.001), whereas there was a gradual increase in MMP-2 (65 kDa) activity, reaching a peak at 5 days (P<0.001). Similarly, quantitative real time polymerase chain reaction (qRT-PCR) indicated significant elevations in MMP-9 and MMP-2 mRNA expression in the injured cortex (P<0.05) and hippocampus (P<0.05) at 1 and 5 days post-injury, respectively in the P21 rat brain. In the P3 rat brain, zymography results revealed that both pro (92 kDa) and cleaved (87 kDa) MMP-9 activities were upregulated in the ipsilateral injured hemisphere from 6 h to 1 day after injury (P<0.001). In contrast, cleaved MMP-2 (60 kDa) was only moderately upregulated at 6 h (P<0.01), while pro MMP-2 (65 kDa) levels were unaffected. MMP-9 mRNA expression was also increased at 6 h (P<0.05) following injury at P3, whereas MMP-2 expression remained unchanged compared with the uninjured contralateral hemisphere. Immunohistochemistry indicated that MMP-9 protein expression was localized predominantly to neurons and perivascular astrocytes in the affected regions at early time points, whereas MMP-2 was present on reactive astrocytes surrounding the infarct at later time points. Together, these results indicate that MMP-2 may be primarily associated with the development and differentiation of cortical plate neurons and wound recovery processes. Conversely, MMP-9 appeared to be associated with more acute processes during the period of lesion development.</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":48596768,"attachmentType":"pdf","workUrl":"https://www.academia.edu/28271669/Proteolytic_activity_during_cortical_development_is_distinct_from_that_involved_in_hypoxic_ischemic_injury"}">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":48596768,"attachmentType":"pdf","workUrl":"https://www.academia.edu/28271669/Proteolytic_activity_during_cortical_development_is_distinct_from_that_involved_in_hypoxic_ischemic_injury"}"><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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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="1" 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="2" 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="3" data-entity-id="12522595" 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/12522595/Study_on_changes_of_MMP_3_expression_after_brain_contusion_in_rats">Study on changes of MMP-3 expression after brain contusion in rats</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="31409068" href="https://independent.academia.edu/BaoliZhu">Baoli Zhu</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Legal Medicine, 2009</p><p class="ds-related-work--abstract ds2-5-body-sm">Forensic pathology Matrix metalloproteinase-3 (MMP-3) Brain contusion Estimating the age of traumatic brain contusion a b s t r a c t To investigate the mechanism and to explore the applicability of MMP-3 (matrix metalloproteinase-3) to determine the age of brain contusion, expression of MMP-3 was studied by immunochemistry and Western blot techniques on model of brain contusion in rats. Brain contusion was performed by falling weight in adult male Sprague-Dawley rats after anesthetized with diethyl ether, then maintained with 2% pentobarbital sodium (30 mg/kg). Samples were collected at 6 and 12 h, 1, 3, 5, 7, 10 and 14 days after the contusion. Histopathological examination and immunostaining of MMP-3 were conducted using paraffin sections. Protein of MMP-3 bands was visualized by ECL kit in Western blot. Result showed that: No staining in control and sham operation group. The staining of MMP-3 positive appeared 6 h after contusion, and it becomes stronger 24 h after contusion, the staining reached the maximum at 5 days post-contusion, then it decrease, positive staining could still be observed at 14 days after contusion. No MMP-3 expression was detected in control and sham group by Western blot analysis. Brain contusion caused the appearance of a band of 45 ku molecular weight, which corresponds to an active form of MMP-3. Conclusions were drew that there is no expression of MMP-3 in normal brain, that the expression of MMP-3 appears 6 h after TBI, and that there is a relationship between the expression of MMP-3 and the time course after TBI, and MMP-3 would be used as an indicator for estimating the age of traumatic brain contusion in forensic pathology.</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":"Study on changes of MMP-3 expression after brain contusion in rats","attachmentId":46117692,"attachmentType":"pdf","work_url":"https://www.academia.edu/12522595/Study_on_changes_of_MMP_3_expression_after_brain_contusion_in_rats","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/12522595/Study_on_changes_of_MMP_3_expression_after_brain_contusion_in_rats"><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="58326022" 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/58326022/Quantitative_analyses_of_matrix_metalloproteinase_activity_after_traumatic_brain_injury_in_adult_rats">Quantitative analyses of matrix metalloproteinase activity after traumatic brain injury in adult rats</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="65110766" href="https://independent.academia.edu/TakuroHayashi">Takuro Hayashi</a></div><p class="ds-related-work--metadata ds2-5-body-xs">2009</p><p class="ds-related-work--abstract ds2-5-body-sm">Recent laboratory evidence implicates matrix metalloproteinases (MMPs) as playing a pivotal role in ischemic and traumatic brain injuries (TBI). Here, quantitative real-time PCR analyses revealed that brains from TBI rats displayed significantly elevated MMP-9 expression at 24 h post-TBI, which remained upregulated at least until 48 h after injury. Immunohistochemical analyses similarly revealed significantly increased MMP-9 immunoreactivity at 24 and 48 h post-TBI. These results demonstrate that alterations in MMPs (i.e., MMP-9) commenced immediately after TBI, suggesting that treatment strategies designed to maintain MMP integrity should be initiated in the acute phase of 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":"Quantitative analyses of matrix metalloproteinase activity after traumatic brain injury in adult rats","attachmentId":72792962,"attachmentType":"pdf","work_url":"https://www.academia.edu/58326022/Quantitative_analyses_of_matrix_metalloproteinase_activity_after_traumatic_brain_injury_in_adult_rats","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/58326022/Quantitative_analyses_of_matrix_metalloproteinase_activity_after_traumatic_brain_injury_in_adult_rats"><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="31758026" 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/31758026/Delayed_administration_of_a_matrix_metalloproteinase_inhibitor_limits_progressive_brain_injury_after_hypoxia_ischemia_in_the_neonatal_rat">Delayed administration of a matrix metalloproteinase inhibitor limits progressive brain injury after hypoxia-ischemia in the neonatal 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="61158610" href="https://independent.academia.edu/ChristopherLeonardo1">Christopher Leonardo</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="61139448" href="https://uams.academia.edu/PaulGottschall">Paul Gottschall</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Neuroinflammation, 2008</p><p class="ds-related-work--abstract ds2-5-body-sm">Background: Hypoxia-ischemia (H-I) can produce widespread neurodegeneration and deep cerebral white matter injury in the neonate. Resident microglia and invading leukocytes promote lesion progression by releasing reactive oxygen species, proteases and other pro-inflammatory mediators. After injury, expression of the gelatin-degrading matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are thought to result in the proteolysis of extracellular matrix (ECM), activation of cytokines/chemokines, and the loss of vascular integrity. Thus, therapies targeting ECM degradation and progressive neuroinflammation may be beneficial in reducing H-I -induced neuropathy. Minocycline has MMP-inhibitory properties and is both anti-inflammatory and neuroprotective. AG3340 (prinomastat) is an MMP inhibitor with high selectivity for the gelatinases. The purpose of this study was to determine whether these compounds could limit H-Iinduced injury when administered at a delayed time point.</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":"Delayed administration of a matrix metalloproteinase inhibitor limits progressive brain injury after hypoxia-ischemia in the neonatal rat","attachmentId":52064366,"attachmentType":"pdf","work_url":"https://www.academia.edu/31758026/Delayed_administration_of_a_matrix_metalloproteinase_inhibitor_limits_progressive_brain_injury_after_hypoxia_ischemia_in_the_neonatal_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/31758026/Delayed_administration_of_a_matrix_metalloproteinase_inhibitor_limits_progressive_brain_injury_after_hypoxia_ischemia_in_the_neonatal_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="6" 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="7" data-entity-id="13451931" 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/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-wsj-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><p class="ds-related-work--abstract ds2-5-body-sm">Background and Purpose-Abnormal expression of some matrix metalloproteinases (MMP) has shown to play a deleterious role in brain injury in experimental models of cerebral ischemia. We aimed to investigate MMP-2 (gelatinase A) and MMP-9 (gelatinase B) in brain parenchyma in both ischemic and hemorrhagic strokes. Methods-Postmortem fresh brain tissue from 6 ischemic and 8 hemorrhagic stroke patients was obtained within the first 6 hours after death. Finally, 78 brain tissue samples from different areas (infarct, peri-infarct, perihematoma and contralateral hemisphere) were studied. To quantify gelatinase content we performed gelatin zymograms that were confirmed by Western Blot Analysis, immunohistochemistry to localize MMP source, and in situ zymography to detect gelatinase activity. Results-Among ischemic cases, gelatin zymography showed increased MMP-9 content in infarct core although peri-infarct tissue presented also higher levels than contralateral hemisphere (PϽ0.0001 and Pϭ0.042, respectively). Within infarct core, MMP-9 was mainly located around blood vessels, associated to neutrophil infiltration and activated microglial cells. In peri-infarct areas the major source of MMP-9 were microglial cells. Tissue around intracranial hemorrhage also displayed higher MMP-9 levels than contralateral hemisphere (Pϭ0.008) in close relationship with glial cells. MMP-2 was constitutively expressed and remained invariable in different brain areas. Conclusions-Our results demonstrate in situ higher levels of MMP-9 in human brain tissue after ischemic and hemorrhagic stroke, suggesting a contribution of MMP-9 to ischemic brain injury and perihematoma edema. (Stroke. 2006;37:1399-1406.)</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-wsj-grid-card-view-pdf" href="https://www.academia.edu/13451931/Increased_Brain_Expression_of_Matrix_Metalloproteinase_9_After_Ischemic_and_Hemorrhagic_Human_Stroke"><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="18531806" 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/18531806/Matrix_metalloproteinases_inhibition_provides_neuroprotection_against_hypoxia_ischemia_in_the_developing_brain">Matrix metalloproteinases inhibition provides neuroprotection against hypoxia-ischemia in the developing brain</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="38563370" href="https://llu.academia.edu/RichardHartman">Richard E Hartman</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Neurochemistry, 2009</p><p class="ds-related-work--abstract ds2-5-body-sm">Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases which are capable of degrading many types of extracellular matrix proteins and involved in the process of tissue remodeling in various pathologic conditions, including inflammatory diseases, tumor cell invasion, and angiogenesis. Previous studies suggest that MMPs, in particular MMP-2 and MMP-9, are deleterious in the brain after stroke . In acute stage after ischemic stroke, the effect of MMP activity is correlated to degradation of neurovascular matrix and opening of blood-brain barrier (BBB), which promotes vasogenic edema and results in neurological deficits. However, recent studies suggest that MMPs were also indicated to be involved in the repairing phase in the delayed stage after cerebral ischemia, including neuroblasts migration and neuronal plasticity ). metalloproteinase; PBS, phosphate-buffered saline; TIMP, tissue inhibitor of metalloproteinase; TJP, tight junction protein, ZO-1, zonula occludens-1.</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 inhibition provides neuroprotection against hypoxia-ischemia in the developing brain","attachmentId":40114460,"attachmentType":"pdf","work_url":"https://www.academia.edu/18531806/Matrix_metalloproteinases_inhibition_provides_neuroprotection_against_hypoxia_ischemia_in_the_developing_brain","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/18531806/Matrix_metalloproteinases_inhibition_provides_neuroprotection_against_hypoxia_ischemia_in_the_developing_brain"><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="14219265" 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/14219265/Brain_contusions_induce_a_strong_local_overexpression_of_MMP_9_Results_of_a_pilot_study">Brain contusions induce a strong local overexpression of MMP-9. Results of a pilot 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="232032863" href="https://independent.academia.edu/JoanMontaner1">Joan Montaner</a><span>, </span><a class="js-wsj-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="33202946" href="https://independent.academia.edu/JSahuquillo">Juan Sahuquillo</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Acta neurochirurgica. Supplement, 2008</p><p class="ds-related-work--abstract ds2-5-body-sm">Brain contusions are inflammatory evolutive lesions that induce intracranial pressure increase and edema, contributing to neurological outcome. Matrix metalloproteinases (MMPs) 2 and 9 can degrade the majority of the extracellular matrix components, and are implicated in blood-brain barrier disruption and edema formation. The aim of this study was to investigate MMP-2 and MMP-9 profiles in human brain contusions using zymography. A prospective study was conducted in 20 traumatic brain injury patients where contusion brain tissue was resected. Brain tissues from lobectomies were used as controls. Brain homogenates were analysed by gelatin zymography and in situ zimography was performed to confirm results, on one control and one brain contusion tissue sample. MMP-2 and MMP-9 levels were higher in brain contusions when compared to controls. MMP-9 was high during the first 24 hours and at 48 to 96 hours, whereas MMP-2 was slightly high at 24 to 96 hours. In situ zymography confirmed gel...</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":"Brain contusions induce a strong local overexpression of MMP-9. Results of a pilot study","attachmentId":44451831,"attachmentType":"pdf","work_url":"https://www.academia.edu/14219265/Brain_contusions_induce_a_strong_local_overexpression_of_MMP_9_Results_of_a_pilot_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/14219265/Brain_contusions_induce_a_strong_local_overexpression_of_MMP_9_Results_of_a_pilot_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></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":48596768,"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":48596768,"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_48596768" 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="26745078" 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/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-related-work-grid-card-author ds2-5-body-sm ds2-5-body-link" data-author-id="46811561" 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