{"id":1058,"date":"2026-04-13T20:00:38","date_gmt":"2026-04-13T20:00:38","guid":{"rendered":"http:\/\/brianamaemorgan.com\/?p=1058"},"modified":"2026-04-13T20:00:38","modified_gmt":"2026-04-13T20:00:38","slug":"inhibition-of-matrix-metalloproteinase-did-not-attenuate-hg-induced-neurite-outgrowth-damage","status":"publish","type":"post","link":"https:\/\/brianamaemorgan.com\/?p=1058","title":{"rendered":"\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage"},"content":{"rendered":"

\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage. significantly decreased, indicating WM damage, and matrix metalloproteinase (MMP)-9 activity was significantly increased in the ischemic brain of mice with diabetes mellitus. Subanalysis of similar lesions in mice with and without Canertinib dihydrochloride<\/a> diabetes mellitus demonstrated mice with diabetes mellitus had significantly increased WM damage than in mice without diabetes mellitus (P<0.05). To investigate the mechanism underlying diabetes mellitus-induced WM damage, oxygen glucose deprivation-stressed premature oligodendrocyte and primary cortical neuron cultures were used. High glucose increased MMP-2, MMP-9, cleaved caspase-3 levels, and apoptosis, as well as decreased cell survival and dendrite outgrowth in cultured primary cortical neuron. High glucose increased MMP-9, cleaved caspase-3 level, and apoptosis, and decreased cell proliferation and cell survival in cultured oligodendrocytes. Inhibition of MMP by GM6001 treatment significantly decreased high glucose-induced cell death and apoptosis in cultured primary cortical neuron and oligodendrocytes but did not alter dendrite outgrowth in primary cortical neuron. == Conclusions == Mice with diabetes mellitus have increased brain hemorrhage and show more severely injured WM than mice without diabetes mellitus after stroke. MMP-9 upregulated in mice with diabetes mellitus may exacerbate WM damage after stroke in mice with diabetes mellitus. Keywords:diabetes, mice, stroke, white matter Diabetes mellitus (DM) is a major health problem leading to a higher risk of ischemic stroke and worse outcome compared to that of the general population.1Diabetic subjects are more prone to more and earlier white matter (WM) high-intensity lesions.2We seek to elucidate the changes and mechanisms underlying the adverse effects of diabetes on the impaired WM after stroke. Matrix metalloproteinases (MMP) degrade extracellular matrix proteins and are implicated in bloodbrain barrier (BBB) breakdown and neuronal injury early after stroke.3Disruption of the BBB leads to WM lesions.4,5MMP promote BBB disruption, glial cell activation, and WM lesions after chronic cerebral hypoperfusion.4Ischemic degradation of myelin basic protein is significantly reduced in the WM in MMP-9 knockout mice.6Increased circulating MMP-9 is associated with a high prevalence of large WM Canertinib dihydrochloride hyperintensities in brain ischemia patients.7MMP-9 protein level and activity are augmented in isolated cerebrovessels of the Goto-Kakizaki rats with diabetes.8Whether DM exacerbates WM damage after stroke and whether MMP contribute to this WM damage in mice with DM have not been investigated. == Materials and Methods == == Animal Middle Cerebral Artery Occlusion Model and Experimental Groups == Adult male BKS.Cg-m+\/+Leprdb\/J(db\/db) mice with DM and control db+mice without DM (age, 23 months) were purchased from Jackson Laboratory (Wilmington, MA). Right temporal (60 minutes) middle cerebral artery occlusion (MCAO) was induced using the filament model as previously described.9Mice with MCAO were euthanized 24 hours after MCAO for immunostaining (n=11 per group) and for zymography, Western blot, and real-time polymerase chain reaction (PCR) assays (n=4 per group). == Blood Glucose Measurement == Blood glucose was measured before and 24 hours after MCAO by using test strips for glucose (Polymer Technology System, Indianapolis, IN). == Functional Test == A battery of behavioral tests (modified neurological severity score)10and foot-fault tests11were performed at 1 day after MCAO by an investigator who was blinded to the experimental groups. == Histological and Immunohistochemical Assessment == The brains were fixed in 4% paraformaldehyde. Seven coronal sections of tissue were processed and stained with hematoxylin and eosin for calculation of volume of cerebral infarction and presented as a percentage of the lesion compared with the contralateral hemisphere.12 For immunostaining, a series of 6-m-thick sections were cut from standard paraffin blocks (bregma, -1 mm to +1 mm). Antibody against NG2 (oligodendrocyte progenitor cell marker, 1:100; Chemicon, CA) Canertinib dihydrochloride and amyloid precursor protein (dilution 1:50; Cell Signaling Technology) were used. Bielschowsky silver immunostaining was used to demonstrate axons, and luxol fast blue staining was used to demonstrate myelin.13Control experiments consisted of staining brain coronal tissue sections as outlined, but nonimmune serum was substituted for the primary antibody. The immunostaining analysis was performed by an investigator blinded to the experimental groups. == Immunostaining Quantification == For quantitative measurements of Bielschowsky silver, amyloid precursor protein, luxol fast blue, and NG2, 5 slides from each Rabbit polyclonal to AGMAT<\/a> brain with each slide containing 4 fields from striatum of the ischemic boundary zone were digitized under a 20 objective (Olympus BX40; Olympus) using a 3-CCD color video camera (Sony DXC-970MD; Sony) interfaced with an micro computer.<\/p>\n","protected":false},"excerpt":{"rendered":"

\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage. significantly decreased, indicating WM damage, and matrix metalloproteinase (MMP)-9 activity was significantly increased in the ischemic brain of mice with diabetes mellitus. Subanalysis of similar lesions in mice with and without Canertinib dihydrochloride diabetes mellitus demonstrated mice with diabetes mellitus had significantly increased WM…<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[35],"tags":[],"class_list":["post-1058","post","type-post","status-publish","format-standard","hentry","category-mglu-group-ii-receptors"],"yoast_head":"\n\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage - novel gene encoding with different concentrations of MMP inhibitor<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/brianamaemorgan.com\/?p=1058\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage - novel gene encoding with different concentrations of MMP inhibitor\" \/>\n<meta property=\"og:description\" content=\"\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage. significantly decreased, indicating WM damage, and matrix metalloproteinase (MMP)-9 activity was significantly increased in the ischemic brain of mice with diabetes mellitus. Subanalysis of similar lesions in mice with and without Canertinib dihydrochloride diabetes mellitus demonstrated mice with diabetes mellitus had significantly increased WM...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/brianamaemorgan.com\/?p=1058\" \/>\n<meta property=\"og:site_name\" content=\"novel gene encoding with different concentrations of MMP inhibitor\" \/>\n<meta property=\"article:published_time\" content=\"2026-04-13T20:00:38+00:00\" \/>\n<meta name=\"author\" content=\"admin\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"admin\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/brianamaemorgan.com\\\/?p=1058#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/brianamaemorgan.com\\\/?p=1058\"},\"author\":{\"name\":\"admin\",\"@id\":\"https:\\\/\\\/brianamaemorgan.com\\\/#\\\/schema\\\/person\\\/bcc4e65314cce8c5f26e5395cfab8443\"},\"headline\":\"\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage\",\"datePublished\":\"2026-04-13T20:00:38+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/brianamaemorgan.com\\\/?p=1058\"},\"wordCount\":75,\"articleSection\":[\"mGlu Group II Receptors\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/brianamaemorgan.com\\\/?p=1058\",\"url\":\"https:\\\/\\\/brianamaemorgan.com\\\/?p=1058\",\"name\":\"\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage - novel gene encoding with different concentrations of MMP inhibitor\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/brianamaemorgan.com\\\/#website\"},\"datePublished\":\"2026-04-13T20:00:38+00:00\",\"author\":{\"@id\":\"https:\\\/\\\/brianamaemorgan.com\\\/#\\\/schema\\\/person\\\/bcc4e65314cce8c5f26e5395cfab8443\"},\"breadcrumb\":{\"@id\":\"https:\\\/\\\/brianamaemorgan.com\\\/?p=1058#breadcrumb\"},\"inLanguage\":\"en-US\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\\\/\\\/brianamaemorgan.com\\\/?p=1058\"]}]},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\\\/\\\/brianamaemorgan.com\\\/?p=1058#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"Home\",\"item\":\"https:\\\/\\\/brianamaemorgan.com\\\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\\\/\\\/brianamaemorgan.com\\\/#website\",\"url\":\"https:\\\/\\\/brianamaemorgan.com\\\/\",\"name\":\"novel gene encoding with different concentrations of MMP inhibitor\",\"description\":\"Just another WordPress site\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\\\/\\\/brianamaemorgan.com\\\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"en-US\"},{\"@type\":\"Person\",\"@id\":\"https:\\\/\\\/brianamaemorgan.com\\\/#\\\/schema\\\/person\\\/bcc4e65314cce8c5f26e5395cfab8443\",\"name\":\"admin\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"en-US\",\"@id\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/0a210e2a6df41be52715ea62f5a55a00b9e79becb4a0775c1a43d6245a8fd5b1?s=96&d=mm&r=g\",\"url\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/0a210e2a6df41be52715ea62f5a55a00b9e79becb4a0775c1a43d6245a8fd5b1?s=96&d=mm&r=g\",\"contentUrl\":\"https:\\\/\\\/secure.gravatar.com\\\/avatar\\\/0a210e2a6df41be52715ea62f5a55a00b9e79becb4a0775c1a43d6245a8fd5b1?s=96&d=mm&r=g\",\"caption\":\"admin\"},\"sameAs\":[\"http:\\\/\\\/brianamaemorgan.com\"],\"url\":\"https:\\\/\\\/brianamaemorgan.com\\\/?author=1\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage - novel gene encoding with different concentrations of MMP inhibitor","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/brianamaemorgan.com\/?p=1058","og_locale":"en_US","og_type":"article","og_title":"\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage - novel gene encoding with different concentrations of MMP inhibitor","og_description":"\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage. significantly decreased, indicating WM damage, and matrix metalloproteinase (MMP)-9 activity was significantly increased in the ischemic brain of mice with diabetes mellitus. Subanalysis of similar lesions in mice with and without Canertinib dihydrochloride diabetes mellitus demonstrated mice with diabetes mellitus had significantly increased WM...","og_url":"https:\/\/brianamaemorgan.com\/?p=1058","og_site_name":"novel gene encoding with different concentrations of MMP inhibitor","article_published_time":"2026-04-13T20:00:38+00:00","author":"admin","twitter_card":"summary_large_image","twitter_misc":{"Written by":"admin"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/brianamaemorgan.com\/?p=1058#article","isPartOf":{"@id":"https:\/\/brianamaemorgan.com\/?p=1058"},"author":{"name":"admin","@id":"https:\/\/brianamaemorgan.com\/#\/schema\/person\/bcc4e65314cce8c5f26e5395cfab8443"},"headline":"\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage","datePublished":"2026-04-13T20:00:38+00:00","mainEntityOfPage":{"@id":"https:\/\/brianamaemorgan.com\/?p=1058"},"wordCount":75,"articleSection":["mGlu Group II Receptors"],"inLanguage":"en-US"},{"@type":"WebPage","@id":"https:\/\/brianamaemorgan.com\/?p=1058","url":"https:\/\/brianamaemorgan.com\/?p=1058","name":"\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage - novel gene encoding with different concentrations of MMP inhibitor","isPartOf":{"@id":"https:\/\/brianamaemorgan.com\/#website"},"datePublished":"2026-04-13T20:00:38+00:00","author":{"@id":"https:\/\/brianamaemorgan.com\/#\/schema\/person\/bcc4e65314cce8c5f26e5395cfab8443"},"breadcrumb":{"@id":"https:\/\/brianamaemorgan.com\/?p=1058#breadcrumb"},"inLanguage":"en-US","potentialAction":[{"@type":"ReadAction","target":["https:\/\/brianamaemorgan.com\/?p=1058"]}]},{"@type":"BreadcrumbList","@id":"https:\/\/brianamaemorgan.com\/?p=1058#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/brianamaemorgan.com\/"},{"@type":"ListItem","position":2,"name":"\ufeffInhibition of matrix metalloproteinase did not attenuate HG-induced neurite outgrowth damage"}]},{"@type":"WebSite","@id":"https:\/\/brianamaemorgan.com\/#website","url":"https:\/\/brianamaemorgan.com\/","name":"novel gene encoding with different concentrations of MMP inhibitor","description":"Just another WordPress site","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/brianamaemorgan.com\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-US"},{"@type":"Person","@id":"https:\/\/brianamaemorgan.com\/#\/schema\/person\/bcc4e65314cce8c5f26e5395cfab8443","name":"admin","image":{"@type":"ImageObject","inLanguage":"en-US","@id":"https:\/\/secure.gravatar.com\/avatar\/0a210e2a6df41be52715ea62f5a55a00b9e79becb4a0775c1a43d6245a8fd5b1?s=96&d=mm&r=g","url":"https:\/\/secure.gravatar.com\/avatar\/0a210e2a6df41be52715ea62f5a55a00b9e79becb4a0775c1a43d6245a8fd5b1?s=96&d=mm&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/0a210e2a6df41be52715ea62f5a55a00b9e79becb4a0775c1a43d6245a8fd5b1?s=96&d=mm&r=g","caption":"admin"},"sameAs":["http:\/\/brianamaemorgan.com"],"url":"https:\/\/brianamaemorgan.com\/?author=1"}]}},"_links":{"self":[{"href":"https:\/\/brianamaemorgan.com\/index.php?rest_route=\/wp\/v2\/posts\/1058","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/brianamaemorgan.com\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/brianamaemorgan.com\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/brianamaemorgan.com\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/brianamaemorgan.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1058"}],"version-history":[{"count":1,"href":"https:\/\/brianamaemorgan.com\/index.php?rest_route=\/wp\/v2\/posts\/1058\/revisions"}],"predecessor-version":[{"id":1059,"href":"https:\/\/brianamaemorgan.com\/index.php?rest_route=\/wp\/v2\/posts\/1058\/revisions\/1059"}],"wp:attachment":[{"href":"https:\/\/brianamaemorgan.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1058"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/brianamaemorgan.com\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1058"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/brianamaemorgan.com\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1058"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}