{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T07:20:57Z","timestamp":1784704857660,"version":"3.55.0"},"reference-count":84,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Neurological Disorders and Stroke","award":["7R01NS110370-06"],"award-info":[{"award-number":["7R01NS110370-06"]}]},{"name":"Division of Biomedical Sciences, School of Medicine at the University of California, Riverside","award":["7R01NS110370-06"],"award-info":[{"award-number":["7R01NS110370-06"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ischemic stroke followed by reperfusion (IR) leads to extensive cerebrovascular injury characterized by neuroinflammation and brain cell death. Inhibition of matrix metalloproteinase-3 (MMP-3) emerges as a promising therapeutic approach to mitigate IR-induced stroke injury. We employed middle cerebral artery occlusion with subsequent reperfusion (MCAO\/R) to model ischemic stroke in adult mice. Specifically, we investigated the impact of MMP-3 knockout (KO) on stroke pathophysiology using RNA sequencing (RNA-seq) of stroke brains harvested 48 h post-MCAO. MMP-3 KO significantly reduced brain infarct size following stroke. Notably, RNA-seq analysis showed that MMP-3 KO altered expression of 333 genes (252 downregulated) in male stroke brains and 3768 genes (889 downregulated) in female stroke brains. Functional pathway analysis revealed that inflammation, integrin cell surface signaling, endothelial- and epithelial-mesenchymal transition (EndMT\/EMT), and apoptosis gene signatures were decreased in MMP-3 KO stroke brains. Intriguingly, MMP-3 KO downregulated gene signatures more profoundly in females than in males, as indicated by greater negative enrichment scores. Our study underscores MMP-3 inhibition as a promising therapeutic strategy, impacting multiple cellular pathways following stroke.<\/jats:p>","DOI":"10.3390\/ijms25137383","type":"journal-article","created":{"date-parts":[[2024,7,8]],"date-time":"2024-07-08T12:21:03Z","timestamp":1720441263000},"page":"7383","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["MMP-3 Knockout Induces Global Transcriptional Changes and Reduces Cerebral Infarction in Both Male and Female Models of Ischemic Stroke"],"prefix":"10.3390","volume":"25","author":[{"given":"Milton H.","family":"Hamblin","sequence":"first","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA"},{"name":"Health Sciences Center, Tulane University, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin C.","family":"Boese","sequence":"additional","affiliation":[{"name":"School of Medicine, Emory University, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5297-8307","authenticated-orcid":false,"given":"Rabi","family":"Murad","sequence":"additional","affiliation":[{"name":"Bioinformatics, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pyo","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, CA 92521, USA"},{"name":"Department of Physiology, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e139","DOI":"10.1161\/CIR.0000000000000757","article-title":"Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association","volume":"141","author":"Virani","year":"2020","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/S0140-6736(13)61953-4","article-title":"Global and regional burden of stroke during 1990\u20132010: Findings from the Global Burden of Disease Study 2010","volume":"383","author":"Feigin","year":"2014","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.neuron.2010.07.002","article-title":"The Science of Stroke: Mechanisms in Search of Treatments","volume":"67","author":"Moskowitz","year":"2010","journal-title":"Neuron"},{"key":"ref_4","first-page":"e85","article-title":"Heart disease and stroke statistics\u20142006 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee","volume":"113","author":"Thom","year":"2006","journal-title":"Circulation"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3727\/096368910X532800","article-title":"Vascular protection and restorative therapy in ischemic stroke","volume":"20","author":"Yamashita","year":"2011","journal-title":"Cell Transplant."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1007\/s00062-015-0478-8","article-title":"Impact of the Implementation of Thrombectomy with Stent Retrievers on the Frequency of Hemicraniectomy in Patients with Acute Ischemic Stroke","volume":"27","author":"Sporns","year":"2017","journal-title":"Clin. 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