miR-137 prevents inflammatory response, oxidative stress, neuronal injury and cognitive impairment via blockade of Src-mediated MAPK signaling pathway in ischemic stroke

Stroke is a leading cause of death and disability worldwide. The purpose of this study was to investigate the possible role of the microRNA (miRNA or miR) miR-137 in ischemic stroke. miRNAs are very stable in the blood and may serve as potential diagnostic and therapeutic markers. Wild-type, Src(-/-) and miR-137(-/-) mice were treated with p38 siRNA or Erk2 siRNA to identify their roles in the inflammatory response, oxidative stress, neuronal injury and cognitive impairment in brain tissues of mice following middle cerebral artery occlusion (MCAO) operation. We evaluated several factors including; inflammatory responses, oxidative stress, viability and apoptosis of astrocytes in order to identify the functions of miR-137 and Src in ischemic stroke. miR-137 alleviated the inflammatory response, oxidative stress, neuronal injury and cognitive impairment, and restricted apoptosis via targeting Src and inactivating the MAPK signaling pathway. Furthermore, up-regulation of miR-137 or inhibition of Src inhibited the secretion of inflammatory factors, suppressed oxidative stress, and reduced apoptosis of astrocytes. In conclusion, our work suggests that, in mice, miR-137 confers neuroprotective effects against ischemic stroke via attenuation of oxidative, apoptotic, and inflammatory pathways through inhibiting Src-dependent MAPK signaling pathway.