Overexpression of miR-149-5p Attenuates Cerebral Ischemia/Reperfusion (I/R) Injury by Targeting Notch2.

Ischemic stroke is one of the leading causes of death and disability worldwide. Although miR-149-5p downregulation is observed in rats after ischemia/reperfusion (I/R) injury, its function and role in ischemic stroke remain unclear. This study aimed to investigate the roles of miR-149-5p in I/R injury. The results showed that miR-149-5p was significantly downregulated in brain tissues of rats subjected to middle cerebral artery occlusion (MCAO) and primary cortical neurons subject to oxygen and glucose deprivation (OGD). MiR-149-5p overexpression effectively reduced MCAO/R-induced infarct volume, neurological score, and brain water content as well as OGD/R-induced cortical neurons apoptosis and OGD/R-induced expression of TNF-α, IL-4, IL-6, IL-1β, and COX-2. Moreover, Notch2 was identified as a target of miR-149-5p and Notch2 overexpression significantly attenuated the inhibitory effects of miR-149-5p mimics on inflammation and apoptosis. Taken together, our study revealed that miR-149-5p overexpression protects the rat brain against I/R injury by regulating Notch2-mediated inflammation and apoptosis pathway.