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Rosiglitazone(RSG), a widely used antidiabetic drug that activates peroxisome proliferator\u2010activated receptor\u2010\u03b3 (PPAR\u2010\u03b3), has been shown to protect against cerebral ischemia through promoting poststroke microglial polarization toward the beneficial anti\u2010inflammatory phenotype. However, whether RSG can alleviate HT after delayed tPA treatment remains unknown. In this study, we sort to examine the role of RSG on tPA\u2010induced HT after stroke.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We used the murine suture middle cerebral artery occlusion (MCAO) models of stroke followed by delayed administration of tPA (10\u00a0mg\/kg, 2\u00a0hours after suture occlusion) to investigate the therapeutic potential of RSG against tPA\u2010induced HT. When RSG(6\u00a0mg\/kg) was intraperitoneally administered 1\u00a0hour before MCAO in tPA\u2010treated MCAO mice, HT in the ischemic territory was significantly attenuated 1\u00a0day after stroke. In the tPA\u2010treated MCAO mice, we found RSG significantly mitigated BBB disruption and hemorrhage development compared to tPA\u2010alone\u2010treated stroke mice. Using flow cytometry and immunostaining, we confirmed that the expression of CD206 was significantly upregulated while the expression of iNOS was down\u2010regulated in microglia of the RSG\u2010treated mice. We further found that the expression of Arg\u20101 was also upregulated in those tPA and RSG\u2010treated stroke mice and the protection against tPA\u2010induced HT and BBB disruption in these mice were abolished in the presence of PPAR\u2010\u03b3 antagonist GW9662 (4\u00a0mg\/kg, 1\u00a0hour before dMCAO through intraperitoneal injection).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>RSG treatment protects against BBB damage and ameliorates HT in delayed tPA\u2010treated stroke mice by activating PPAR\u2010\u03b3 and favoring microglial polarization toward anti\u2010inflammatory phenotype.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13260","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T13:42:05Z","timestamp":1574430125000},"page":"1343-1352","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":52,"title":["Rosiglitazone ameliorates tissue plasminogen 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