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In this study, we investigated whether inhibition of PI3K\u03b2 protects against cerebral ischemia\/reperfusion (I\/R) injury by preventing circulating platelet activation and downstream microvascular thrombosis. We used a rat intraluminal filament model of transient middle cerebral artery occlusion (tMCAO) because the rapid restoration of cerebral blood flow to the ischemic area in both tMCAO and endovascular thrombectomy provides clinical relevance for this model. The results showed that TGX221, a selective PI3K\u03b2 inhibitor, treatment immediately before the onset of reperfusion dose-dependently reduced infarct volume and improved neurological function. The protective effects were associated with blocking platelet activation and thrombotic response, thereby reducing downstream microvascular thrombosis, and maintaining reperfusion efficiency. These results suggest that PI3K\u03b2 might be a promising target for treating downstream microvascular thrombosis induced by cerebral I\/R injury and offer a novel adjunctive treatment to improve reperfusion therapy for acute ischemic stroke.<\/jats:p>","DOI":"10.1038\/s41598-023-29235-2","type":"journal-article","created":{"date-parts":[[2023,2,4]],"date-time":"2023-02-04T06:02:44Z","timestamp":1675490564000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Blocking of PI3-kinase beta protects against cerebral ischemia\/reperfusion injury by reducing platelet activation and downstream microvascular thrombosis in rats"],"prefix":"10.1038","volume":"13","author":[{"given":"Qiong","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohong","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,4]]},"reference":[{"issue":"4","key":"29235_CR1","first-page":"e29","volume":"131","author":"D Mozaffarian","year":"2015","unstructured":"Mozaffarian, D. et al. 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