PRMT8 Attenuates Cerebral Ischemia/Reperfusion Injury via Modulating Microglia Activation and Polarization to Suppress Neuroinflammation by Upregulating Lin28a br

Activation and polarization of microglia are involved in neuroinflammation and regulate ischemic stroke-associated brain injury. Protein arginine methyltransferase 8 functions as a regulatory component of hypoxic stress-induced neuroinflammation. The protective effect of protein arginine methyltransferase 8 (PRMT8) against ischemic stroke-associated brain injury through regulation of microglia activation and polarization was investigated. First, PRMT8 was downregulated in middlecerebral artery occlusion (MCAO)-induced mice and oxygen-glucosedeprivation/reoxygenation (OGD/R)-induced SH-SY5Y. Injection withAAV-PRMT8 reduced infarct volumes in MCAO-induced mice. More-over, injection with AAV-PRMT8 promoted neuronal survival andameliorated histopathological changes in the brains of MCAO-inducedmice. The neuronal apoptosis and neuroinflammation in MCAO-inducedmice were suppressed by AAV-PRMT8 injection. Second, PRMT8overexpression increased cell viability and suppressed the cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. Third ,injection with AAV-PRMT8 reduced almost 50% of CD86 + M1 microglia and enhanced about 20% of CD206 + M2 microglia. Furthermore, PRMT8 overexpression attenuated OGD/R-induced M1 phenotype polarization of BV2. Lastly, PRMT8 upregulatedLin28a and loss of Lin28a attenuated PRMT8 overexpression-induced increase in cell viability and decrease in cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. In conclusion, PRMT8 promoted M2 phenotype polarization of microglia and suppressed neuronal apoptosis to ameliorate cerebral ischemia/reperfusion injury through upregulation of Lin28a