Exosomal miR-370-3p increases the permeability of blood-brain barrier in ischemia/reperfusion stroke of brain by targeting MPK1

Abstract

Ischemia/reperfusion (I/R) damage induced by stroke poses a serious hazard to human life, while mechanism of blood-brain barrier (BBB) dysfunction is still unknown. To imitate stroke induced ischemia conditions in vivo, the rat model of cerebral I/R damage was created by middle cerebral artery occlusion (MCAO). In vitro, the rat microvascular endothelial cell line bEND.3 was subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Evans blue was used to evaluate the permeability of the blood-brain barrier (BBB). To evaluate gene expression at the mRNA and protein levels, researchers used real-time PCR and western blotting. Infarct volume and BBB permeability were considerably higher in cerebral (I/R) animals than in the Sham group. Exosomal miR-370-3p expression was shown to be higher in the brains of I/R injured rats and OGD/R treatment bEND.3. The BBB permeability was considerably increased when miR-370-3p was downregulated in OGD/R pretreated bEND.3. miR-370-3p regulates MAPK1 expression by targeting it. In bEND.3, OGD/R therapy increased BBB permeability substantially. OGD/R was inhibited by miR-370-3p mimic transfection, while miR-370-3p mimic was abolished by co-transfection with MAPK1 overexpression lentivirus. In cerebral I/R damage, exosomal miR-370-3p targets MAPK1 and aggregates BBB permeability.