Blocking of PI3-kinase beta protects against cerebral ischemia/reperfusion injury by reducing platelet activation and downstream microvascular thrombosis in rats

• Published in: Scientific reports Vol. 13; no. 1; p. 2030
• Main Authors: Cheng, Qiong, Wang, Min, Jin, Rong, Li, Guohong
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 04.02.2023; Nature Publishing Group UK; Nature Portfolio
• Subjects: 1-Phosphatidylinositol 3-kinase; Animals; Blood flow; Blood platelets; Brain Ischemia - drug therapy; Cardiovascular system; Cerebral blood flow; Infarction, Middle Cerebral Artery - pathology; Ischemia; Ischemic Stroke; Microvasculature; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Platelet Activation; Platelets; Rats; Reperfusion; Reperfusion Injury - drug therapy; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Stroke; Thromboembolism; Thrombosis; Thrombosis - drug therapy; Thrombosis - prevention & control
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-29235-2

Phosphoinositide 3-kinase beta (PI3Kβ) plays an important role in platelet activation and thrombosis, but its role in stroke pathology remains unknown. In this study, we investigated whether inhibition of PI3Kβ 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 PI3Kβ 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 PI3Kβ 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.