{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:42:32Z","timestamp":1791585752227,"version":"4.3.4"},"reference-count":53,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T00:00:00Z","timestamp":1724976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. National Institutes of Health","award":["R01NS89707"],"award-info":[{"award-number":["R01NS89707"]}]},{"name":"U.S. National Institutes of Health","award":["HL146676"],"award-info":[{"award-number":["HL146676"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Matrix metalloproteinases (MMPs) such as MMP-9, 3, and 2 degrade the cellular matrix and are believed to play a crucial role in ischemic stroke. We examined how the duration of ischemia (up to 4 h) and treatment with recombinant tissue plasminogen activator altered the comparative expression of these MMPs in experimental ischemic stroke with reperfusion. Both prolonged ischemia and r-tPA treatment markedly increased MMP-9 expression in the ischemic hemisphere (all p &lt; 0.0001). The duration of ischemia and r-tPA treatment also significantly increased MMP-2 expression (p &lt; 0.01\u20130.001) in the ischemic hemisphere (p &lt; 0.01) but to a lesser degree than MMP-9. In contrast, MMP-3 expression significantly decreased in the ischemic hemisphere (p &lt; 0.001) with increasing duration of ischemia and r-tPA treatment (p &lt; 0.05\u20130001). MMP-9 expression was prominent in the vascular compartment and leukocytes. MMP-2 expression was evident in the vascular compartment and MMP-3 in NeuN+ neurons. Prolonging the duration of ischemia (up to 4 h) before reperfusion increased brain hemorrhage, infarction, swelling, and neurologic disability in both saline-treated (control) and r-tPA-treated mice. MMP-9 and MMP-2 expression were significantly positively correlated with, and MMP-3 was significantly negatively correlated with, infarct volume, swelling, and brain hemorrhage. We conclude that in experimental ischemic stroke with reperfusion, the duration of ischemia and r-tPA treatment significantly altered MMP-9, 3, and 2 expression, ischemic brain injury, and neurological disability. Each MMP showed unique patterns of expression that are strongly correlated with the severity of brain infarction, swelling, and hemorrhage. In summary, in experimental ischemic stroke in male mice with reperfusion, the duration of ischemia, and r-tPA treatment significantly altered the immunofluorescent expression of MMP-9, 3, and 2, ischemic brain injury, and neurological disability. In this model, each MMP showed unique patterns of expression that were strongly correlated with the severity of brain infarction, swelling, and hemorrhage.<\/jats:p>","DOI":"10.3390\/ijms25179442","type":"journal-article","created":{"date-parts":[[2024,8,30]],"date-time":"2024-08-30T09:39:32Z","timestamp":1725010772000},"page":"9442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Differences in Acute Expression of Matrix Metalloproteinases-9, 3, and 2 Related to the Duration of Brain Ischemia and Tissue Plasminogen Activator Treatment in Experimental Stroke"],"prefix":"10.3390","volume":"25","author":[{"given":"Dong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofiyan","family":"Saleem","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7633-2210","authenticated-orcid":false,"given":"Ryan D.","family":"Sullivan","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tieqiang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guy L.","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Arizona College of Medicine, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1227\/NEU.0000000000001264","article-title":"Neuroprotective Effects of Valproic Acid on Blood-Brain Barrier Disruption and Apoptosis-Related Early Brain Injury in Rats Subjected to Subarachnoid Hemorrhage Are Modulated by Heat Shock Protein 70\/Matrix Metalloproteinases and Heat Shock Protein 70\/AKT Pathways","volume":"79","author":"Ying","year":"2016","journal-title":"Neurosurgery"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/sj.jcbfm.9600375","article-title":"Matrix Metalloproteinase-Mediated Disruption of Tight Junction Proteins in Cerebral Vessels is Reversed by Synthetic Matrix Metalloproteinase Inhibitor in Focal Ischemia in Rat","volume":"27","author":"Yang","year":"2007","journal-title":"J. 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