Abstract TP270: MicroRNA-383-5p Alleviates Hemorrhagic Transformation and Improves Outcomes after Mechanical Reperfusion for Acute Ischemic Stroke

Background: Hemorrhage transformation (HT) following endovascular reperfusion treatment is associated with poor clinical outcomes in acute ischemic stroke patients. MicroRNAs modulate several aspects of cerebral ischemia-reperfusion injury, including blood-brain barrier (BBB) integrity, inflammation, oxidative stress, and apoptosis, significantly impacting cerebral recovery and function. This study investigated the role of microRNA-383 in HT in the oxygen-glucose deprivation reoxygenation (OGD/R) model of neurons and the transient middle cerebral artery occlusion (MCAO) model. Methods: The isoforms of 5p and 3p of miR-383, the family of nicotinamide adenine dinucleotide phosphate oxidase (NOX), peroxiredoxin (PRDX), toll-like receptor, and caspase expression in the OGD/R mice neuron model were assessed. The neuronal injury, neuronal apoptosis, the expression of reactive oxygen species (ROS), and the regulation of miR-383-5p target genes were evaluated after the miR-383-5p and small interfering RNA intervention. A mechanical reperfusion-induced HT model was established in hyperglycemic rats using 5-hour MCAO followed by 3 hours and 6 hours of reperfusion. MiR-383-5p agomir was administered intravenously before reperfusion. Infarct volume, brain water content, HT, neurological score, BBB damage, neuronal apoptosis, ROS, the expression of miR-383-5p and its target genes, and BBB-associated proteins were evaluated. Results: MiR-383-5p expression significantly decreased in OGD/R-treated neurons, while miR-383-3p expression did not differ. The expression of NOX2, NOX3, NOX4, PRDX1, PRDX3, PRDX4, PRDX5, and PRDX6 increased in neurons after OGD/R. Elevating miR-383-5p levels reduced neuronal injury, neuronal apoptosis, ROS expression, and suppressed the expression of its direct target genes, NOX4 and PRDX3, in the OGD/R model. Intravenous administration of miR-383-5p agomir increased the expression of miR-383-5p, suppressed the upregulation of NOX4 and PRDX3, and reduced infarct volume, brain edema, reperfusion-induced HT, BBB breakdown, neuronal apoptosis, and ROS after ischemia, improving neurological outcomes in the MCAO model. Conclusions: MiR-383-5p alleviates neuronal injury, oxidative stress, and apoptosis in neurons subjected to ischemia-reperfusion injury by regulating NOX4 and PRDX3. Neuronal miR-383-5p may be a protective target for reducing hemorrhagic transformation and improving outcomes following mechanical reperfusion in acute ischemic stroke.