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(PDF) Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice
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"https://www.academia.edu/login?post_login_redirect_url=https%3A%2F%2Fwww.academia.edu%2F33718248%2FDifferential_alterations_in_the_expression_and_activity_of_matrix_metalloproteinases_2_and_9_after_transient_cerebral_ischemia_in_mice%3Fshow_translation%3Dtrue"; window.loswp.previewableAttachments = [{"id":53714994,"identifier":"Attachment_53714994","shouldShowBulkDownload":false}]; window.loswp.shouldDetectTimezone = true; window.loswp.shouldShowBulkDownload = true; window.loswp.showSignupCaptcha = false window.loswp.willEdgeCache = false; window.loswp.work = {"work":{"id":33718248,"created_at":"2017-06-30T09:24:58.234-07:00","from_world_paper_id":162991163,"updated_at":"2024-11-14T07:24:09.826-08:00","_data":{"grobid_abstract":"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.","publication_date":"2004,,","publication_name":"Neurobiology of Disease","grobid_abstract_attachment_id":"53714994"},"document_type":"paper","pre_hit_view_count_baseline":null,"quality":"high","language":"en","title":"Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice","broadcastable":true,"draft":null,"has_indexable_attachment":true,"indexable":true}}["work"]; window.loswp.workCoauthors = [66014727]; 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":53714994,"attachmentType":"pdf"}"><img alt="First page of “Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice”" class="ds-work-cover--cover-thumbnail" src="https://0.academia-photos.com/attachment_thumbnails/53714994/mini_magick20190119-829-16y3yw1.png?1547954049" /><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">Differential alterations in the expression and activity of matrix metalloproteinases 2 and 9 after transient cerebral ischemia in mice</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="66014727" href="https://independent.academia.edu/SarahGeorge40"><img alt="Profile image of Sarah George" class="ds-work-card--author-avatar" src="//a.academia-assets.com/images/s65_no_pic.png" />Sarah George</a></div><div class="ds-work-card--detail"><p class="ds-work-card--detail ds2-5-body-sm">2004, Neurobiology of Disease</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">10 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 = 33718248; 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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">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. 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In this study, we investigated the time course of gelatinolytic activation in a rat model of permanent ischemia. We observed an activation of MMPs as early as 30 mins after the ischemic insult, mainly in the nuclei of brain cells. Besides, we explored MMP-13 expression in brain samples of the animal model and stroke deceased patients. We observed an upregulation of active MMP-13 in rat brains ( P&lt; 0.05) after 90 mins of cerebral ischemia. Human infarct/periinfarct samples also showed higher levels of active MMP-13 ( P&lt; 0.05) compared with contralateral ones. Interestingly, we found that MMP-13 colocalized with 46-diamidino-2-phenyl indole signal by immunohistochemistry in both humans and rats, suggesting an intranuclear localization for MMP-13. Immunohistochemistry also revealed that MMP-13 was mainly produced by neurons, in both species, but also by oligodendrocytes in rats, and b...</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-wsj-grid-card-view-pdf" href="https://www.academia.edu/96355178/Matrix_Metalloproteinase_13_is_Activated_and_is_found_in_the_Nucleus_of_Neural_Cells_after_Cerebral_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="1" data-entity-id="22209202" 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/22209202/In_Vivo_Evidence_that_the_Increase_in_Matrix_Metalloproteinase_Activity_Occurs_Early_after_Cerebral_Ischemia">In Vivo Evidence that the Increase in Matrix Metalloproteinase Activity Occurs Early after Cerebral 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="32731095" href="https://inserm.academia.edu/BertrandTavitian">Bertrand Tavitian</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Molecular Imaging, 2012</p><p class="ds-related-work--abstract ds2-5-body-sm">There is controversy over whether matrix metalloproteinases (MMPs) are activated during the early therapeutic window following ischemic stroke. Ex vivo, an increase was reported as early as 4 hours, whereas in vivo, no increase was found until 24 hours postischemia. We used fluorescence diffuse optical tomography to image MMP activity following experimental cerebral ischemia;</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":"In Vivo Evidence that the Increase in Matrix Metalloproteinase Activity Occurs Early after Cerebral Ischemia","attachmentId":42863191,"attachmentType":"pdf","work_url":"https://www.academia.edu/22209202/In_Vivo_Evidence_that_the_Increase_in_Matrix_Metalloproteinase_Activity_Occurs_Early_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-wsj-grid-card-view-pdf" href="https://www.academia.edu/22209202/In_Vivo_Evidence_that_the_Increase_in_Matrix_Metalloproteinase_Activity_Occurs_Early_after_Cerebral_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="2" 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 class="ds-related-work--container js-wsj-grid-card" data-collection-position="3" data-entity-id="13674470" 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/13674470/Matrix_metalloproteinase_2_gene_knockout_has_no_effect_on_acute_brain_injury_after_focal_ischemia">Matrix metalloproteinase 2 gene knockout has no effect on acute brain injury after focal 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="32820256" href="https://riken.academia.edu/ShigeyoshiItohara">Shigeyoshi Itohara</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neuroreport, 2001</p><p class="ds-related-work--abstract ds2-5-body-sm">Matrix metalloproteinases (MMPs) may contribute to tissue damage after cerebral ischemia. In this study, wildtype and MMP-2 knockout mice were subjected to permanent and transient (2 h) occlusions of the middle cerebral artery. Gelatin zymography showed that MMP-9 levels were increased in all brains after ischemia. MMP-2 levels did not show a significant increase in wildtype mice, and were not detectable in knockout mice. Laser doppler flowmetry demonstrated equivalent ischemic reductions in perfusion in wildtype and knockout mice. In both permanent and transient occlusion paradigms, there were no statistically significant differences between wildtype and knockout mice in terms of 24 h ischemic lesion volumes. These data suggest that MMP-2 does not contribute to acute tissue damage in this model of focal ischemia.</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 gene knockout has no effect on acute brain injury after focal ischemia","attachmentId":49906701,"attachmentType":"pdf","work_url":"https://www.academia.edu/13674470/Matrix_metalloproteinase_2_gene_knockout_has_no_effect_on_acute_brain_injury_after_focal_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/13674470/Matrix_metalloproteinase_2_gene_knockout_has_no_effect_on_acute_brain_injury_after_focal_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="4" 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="5" data-entity-id="96355312" 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/96355312/Matrix_metalloproteinase_13_participates_in_neuroprotection_and_neurorepair_after_cerebral_ischemia_in_mice">Matrix metalloproteinase-13 participates in neuroprotection and neurorepair after 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="232032863" href="https://independent.academia.edu/JoanMontaner1">Joan Montaner</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Neurobiology of Disease, 2016</p><p class="ds-related-work--abstract ds2-5-body-sm">New neuroreparative and neuroprotective therapies are being sought to treat stroke patients. One approach is the remodeling of extracellular matrix, which participates in both brain injury and neurovascular repair when matrix metalloproteinases (MMPs) are thought to be key players. Our aim was to investigate the role of MMP-13 (collagenase-3) in the acute (24 hours and 3 days) and delayed (2 weeks) phases of stroke. Permanent and transient cerebral ischemia models involving the cortex were induced in MMP-13 knockout (KO) and wild-type (WT) mice. In the transient model, MMP-13 deficiency reduced the amount of TTC-stained infarct tissue, reduced hemorrhagic events and improved functional outcomes (p<0.01). At two weeks, normal neuroblast (DCX+) migration from the subventricular zone toward the peri-infarct area was observed. However, MMP-13 deficiency significantly reduced the number of newborn neuroblasts (DCX+/BrdU+) in the cortical peri-infarct area (p<0.01). This result occurred in parallel with aberrant cortical vascular remodeling: post-stroke peri-infarct vessel density increased in the WT mice (p<0.01) but this increase was blocked in the MMP-13 KO mice. Prior to these vascular alterations, the levels of pro-angiogenic factors, including G-CSF, VEGF-A and angiopoietin-2, were lower in the ischemic cortex of MMP-13 KO mice than in WT mice (p<0.05). In vitro, gene-silencing of MMP-13 in endothelial progenitor cells (EPCs) confirmed the reduced ability of these cells to build tubulogenic networks in Matrigel TM substrate. Together, our results indicate that MMP-13 is a central protease in infarct development and cortical remodeling during post-stroke neurorepair, which is critical for optimal angiogenic and neurogenic responses.</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 participates in neuroprotection and neurorepair after cerebral ischemia in mice","attachmentId":98276002,"attachmentType":"pdf","work_url":"https://www.academia.edu/96355312/Matrix_metalloproteinase_13_participates_in_neuroprotection_and_neurorepair_after_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/96355312/Matrix_metalloproteinase_13_participates_in_neuroprotection_and_neurorepair_after_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="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="15742944" 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/15742944/Involvement_of_Matrix_Metalloproteinase_Mediated_Proteolysis_of_Neural_Cell_Adhesion_Molecule_in_the_Development_of_Cerebral_Ischemic_Neuronal_Damage">Involvement of Matrix Metalloproteinase-Mediated Proteolysis of Neural Cell Adhesion Molecule in the Development of Cerebral Ischemic Neuronal Damage</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="34931339" href="https://independent.academia.edu/ToshitakaNabeshima">Toshitaka Nabeshima</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Journal of Pharmacology and Experimental Therapeutics, 2011</p><p class="ds-related-work--abstract ds2-5-body-sm">Neural cell adhesion molecule (NCAM) is a membrane protein abundantly expressed in the central nervous system. Recently, it has been reported that dysfunction of NCAM is linked to human brain disorders. Furthermore, NCAM is one of the proteolysis targets of matrix metalloproteinase (MMP), whose activation is implicated in neuronal damage. The aim of this study was to elucidate the involvement of MMP-mediated proteolysis of NCAM in the development of ischemic neuronal damage. Male ddY and MMP-9 knockout (KO) C57BL/6J mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). In MCAO model mice, development of infarction and behavioral abnormality were clearly observed on days 1 and 3 after MCAO. Protein levels of MMP-2 and MMP-9 were significantly increased on days 1 and 3 after MCAO. In addition, full-length NCAM (180 kDa) was significantly decreased, but its metabolite levels increased on day 1 by ischemic stress per se. NCAM small interfering RNA significantly increased the neuronal damage induced by MCAO. MMP inhibition or MMP-9 gene KO attenuated the infarction, behavioral abnormalities, and decrease of NCAM (180 kDa) observed after MCAO in mice. The present findings clearly suggest that MMP-2/MMP-9-mediated NCAM proteolysis is implicated in the exacerbation of ischemic neuronal damage.</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":"Involvement of Matrix Metalloproteinase-Mediated Proteolysis of Neural Cell Adhesion Molecule in the Development of Cerebral Ischemic Neuronal Damage","attachmentId":42914005,"attachmentType":"pdf","work_url":"https://www.academia.edu/15742944/Involvement_of_Matrix_Metalloproteinase_Mediated_Proteolysis_of_Neural_Cell_Adhesion_Molecule_in_the_Development_of_Cerebral_Ischemic_Neuronal_Damage","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/15742944/Involvement_of_Matrix_Metalloproteinase_Mediated_Proteolysis_of_Neural_Cell_Adhesion_Molecule_in_the_Development_of_Cerebral_Ischemic_Neuronal_Damage"><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="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="9" data-entity-id="28027757" 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/28027757/Matrix_metalloproteinases_and_diseases_of_the_central_nervous_system_with_a_special_emphasis_on_ischemic_brain">Matrix metalloproteinases and diseases of the central nervous system with a special emphasis on ischemic 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="52543900" href="https://independent.academia.edu/PaolaSoccal">Paola Soccal</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Frontiers in Bioscience, 2006</p><p class="ds-related-work--abstract ds2-5-body-sm">The role of matrix metalloproteinases in glioma invasion. Front Biosci 8, e261-269 (2003)</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 and diseases of the central nervous system with a special emphasis on ischemic brain","attachmentId":48334183,"attachmentType":"pdf","work_url":"https://www.academia.edu/28027757/Matrix_metalloproteinases_and_diseases_of_the_central_nervous_system_with_a_special_emphasis_on_ischemic_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/28027757/Matrix_metalloproteinases_and_diseases_of_the_central_nervous_system_with_a_special_emphasis_on_ischemic_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></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":53714994,"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":53714994,"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_53714994" 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="116955806" 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/116955806/Up_regulation_of_brain_cytokines_and_metalloproteinases_1_and_2_contributes_to_neurological_deficit_and_brain_damage_in_transient_ischemic_stroke">Up-regulation of brain cytokines and metalloproteinases 1 and 2 contributes to neurological deficit and brain damage in transient ischemic 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="35700792" href="https://independent.academia.edu/EdnaConstanzaGomezVictoria">Edna Constanza Gomez Victoria</a></div><p class="ds-related-work--metadata ds2-5-body-xs">Microvascular Research, 2020</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":"Up-regulation of brain cytokines and metalloproteinases 1 and 2 contributes to neurological deficit and brain damage in transient ischemic stroke","attachmentId":112942137,"attachmentType":"pdf","work_url":"https://www.academia.edu/116955806/Up_regulation_of_brain_cytokines_and_metalloproteinases_1_and_2_contributes_to_neurological_deficit_and_brain_damage_in_transient_ischemic_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" href="https://www.academia.edu/116955806/Up_regulation_of_brain_cytokines_and_metalloproteinases_1_and_2_contributes_to_neurological_deficit_and_brain_damage_in_transient_ischemic_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-related-work-sidebar-card" data-collection-position="1" data-entity-id="5282502" 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/5282502/Matrix_Metalloproteinase_Expression_After_Human_Cardioembolic_Stroke_Temporal_Profile_and_Relation_to_Neurological_Impairment">Matrix Metalloproteinase Expression After Human Cardioembolic Stroke Temporal Profile and Relation to Neurological Impairment</a><div class="ds-related-work--metadata"><a 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href="https://www.academia.edu/5282502/Matrix_Metalloproteinase_Expression_After_Human_Cardioembolic_Stroke_Temporal_Profile_and_Relation_to_Neurological_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="2" 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 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