MicroRNA-383-5p regulation of NADPH oxidase 4 alleviates hemorrhagic transformation and improves acute outcomes after endovascular recanalization in acute ischemic stroke

BackgroundHemorrhagic transformation (HT) following reperfusion therapy is associated with poor outcomes in patients with acute ischemic stroke. Here, we determined the role of microRNA-383-5p (miR-383-5p) in alleviating HT-associated injury using models of middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R).MethodsTwo hundred and five hyperglycemic rats were used to establish a model of HT induced by mechanical recanalization after 5 hours of MCAO, followed by 3 and 6 hours of recanalization; then, miR-383-5p agomir was administered intravenously before recanalization.

Analysis involved brain water content; hemorrhage severity; infarct volume; blood-brain barrier (BBB) disruption; neuronal apoptosis, reactive oxygen species (ROS) production; along with the expression levels of miR-383-5p, NADPH oxidase 4 (NOX4), interleukin 1 beta (IL-1β), and BBB-associated proteins. The expression of miR-383-5p and NOX4 was also evaluated in neurons after OGD/R, whereas neuronal injury and ROS production were assessed following intervention with miR-383-5p and small interfering RNA.ResultsIn the MCAO model, intravenous administration of miR-383-5p agomir increased miR-383-5p and suppressed NOX4 upregulation in peri-infarct tissue and in brain microvascular endothelial cells, neurons, and astrocytes, as demonstrated by immunohistochemical fluorescent staining.