MiR-203a-3p/153-3p improves cognitive impairments induced by ischemia/reperfusion via blockade of SRC-mediated MAPK signaling pathway in ischemic stroke

Stroke is a leading cause of death and disability worldwide and the cerebral ischemia/reperfusion (I/R) induced injury is a common phenomenon of stroke. The pathogenesis and effective treatment of I/R-induced brain tissue damage is limited. In this study, the rat model of middle cerebral artery occlusion (MCAO) and the cell model of oxygen and glucose deprivation/reperfusion (OGD/R) were applied to investigate the possible role of the microRNA in ischemic stroke. MCAO/R and OGD/R caused the downregulation of miR-203a-3p and miR-153-3p, the upregulation of SRC. SRC was identified to be a common target for miR-203a-3p and miR-153-3p. Both miR-203a-3p and miR-153-3p inhibited SRC expression at the mRNA and protein levels. miR-203a-3p and miR-153-3p improved the cognitive deficits through targeting SRC. Moreover, miR-203a-3p and miR-153-3p relieved the apoptosis, decreases NLRP3 inflammasome activity, decreases oxidative stress and inflammation in hippocampal neuron through targeting SRC. Moreover, the MAPK signaling pathway was confirmed to be the downstream for miR-203a-3p and miR-153-3p in vivo and in vitro. Thus, miR-203a-3p and miR-153-3p confers neuroprotective effects against ischemic stroke via attenuation of apoptosis, oxidative stress and inflammatory pathways through inhibiting SRC-dependent MAPK signaling pathway in vivo and in vitro, suggesting new therapeutic targets for the prevention and treatment of stroke.