Dynamic Changes in miR-126 Expression in the Hippocampus and Penumbra Following Experimental Transient Global and Focal Cerebral Ischemia–Reperfusion

Abstract

miR-126 which is considered one of the most important miRNAs for maintaining vascular integrity, plays an important role in neuroprotection after cerebral ischemia-reperfusion (I-R). Moreover, vascular endothelial growth factor A (VEGFA), sprouty-related EVH1 domain-containing protein 1 (SPRED1), and Raf-1 are also involved in physiological processes of vascular endothelial cells (ECs). This study investigated how miR-126 changes with reperfusion time in different brain tissues after global cerebral ischemia and focal cerebral ischemia and examined the underlying mechanism miR-126 involving VEGFA, SPRED1, and Raf-1 after I-R. The results indicated decreases in the levels of miR-126-3p and miR-126-5p expression in mice and gerbils after I-R, consistent with the results after oxygen and glucose deprivation and reperfusion (OGD/R) in PC12 cells. Glial cells were activated as neuronal damage gradually increased after I-R. Inhibition of miR-126-3p exacerbated the OGD/R-induced cell death and reduced cell viability. After miR-126-3p inhibition, the levels of SPRED1 and VEGFA expression were increased, and p-Raf-1 expression was decreased after OGD/R. Moreover, based on the intervention of miR-126-3p inhibition, we found that the expression of p-Raf-1 was significantly increased after the intervention of siSPRED1, while it was not statisticallysignificant after intervention of siVEGFA. The reduction of miR-126 expression after global and focal cerebral ischemia exacerbated neuronal death, which was closely related to increasing the SPRED1 activation and inhibiting the Raf-1 expression.