Zhuang, J.-K. | bioRxiv Science

bioRxiv2025

MicroRNA-383-5p alleviates hemorrhagic transformation and improves outcomes after endovascular recanalization for acute ischemic stroke

BackgroundHemorrhage transformation (HT) after reperfusion therapy is linked with poor outcomes in acute ischemic stroke patients. This study aimed to determine the role of neuronal microRNA-383 in alleviating HT-associated injury using middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation reoxygenation (OGD/R) models. MethodsIn neurons following OGD/R, the family of miR-383 and NADPH oxidase (NOX) expression was evaluated. After miR-383-5p intervention and small interfering RNA, reactive oxygen species (ROS) and neuronal injury were assessed. Two hundred and five hyperglycemic rats were used to establish the HT model induced by mechanical reperfusion after 5-hour MCAO, followed by 3 and 6 hours of reperfusion, and treated with intravenous administration of miR-383-5p agomir before reperfusion. Brain water content, hemorrhage severity, infarct volume, blood-brain barrier (BBB) disruption, neuronal apoptosis, ROS production, miR-383-5p and NOX4 expression, and BBB-associated proteins were assessed. ResultsMiR-383-5p expression significantly decreased in OGD/R-treated neurons, while miR-383-3p expression did not differ. Elevating miR-383-5p levels reduced neuronal injury, ROS overproduction, and NOX4 overexpression as a target of miR-383-5p, shown in OGD/R-treated neurons. In the MCAO model, increased miR-383-5p suppressed NOX4 upregulation, alleviated brain edema, infarct volume, and hemorrhage severity, reduced neuronal apoptosis and ROS overproduction, and preserved BBB integrity after mechanical reperfusion for ischemia, thereby improving short-term neurological outcomes. ConclusionsMiR-383-5p alleviates oxidative stress injury and neuronal apoptosis, and preserves BBB integrity by regulating NOX4. Neuronal miR-383-5p could become a potential target for intervention to decrease HT and ameliorate outcomes in endovascular reperfusion treatment for acute ischemic stroke.

neuroscience↗

bioRxiv2024

MicroRNAs and mRNA Regulatory Network of Parenchymal Hematoma after Endovascular Mechanical Reperfusion for Acute Ischemic Stroke in Rat

Hemorrhagic transformation after endovascular thrombectomy predicts poor outcomes in acute ischemic stroke with large vessel occlusion. The roles of microRNAs in the pathogenesis of parenchymal hematoma (PH) are still unclear. This study aims to investigate the microRNA and mRNA regulatory network associated with PH after mechanical reperfusion in the animal stroke model and oxygen-glucose deprivation/reoxygenation (OGD/R) model. Twenty-five microRNAs were assessed in the reperfusion-induced hemorrhage model in rats with hyperglycemic conditions receiving 5-hour middle cerebral artery occlusion. Thirteen down-regulated microRNAs (miRNA-29a-5p, miRNA-29c-3p, miRNA-126a-5p, miRNA-132-3p, miRNA-136-3p, miRNA-142-3p, miRNA-153-5p, miRNA-218a-5p, miRNA-219a-2-3p, miRNA-369-5p, miRNA-376a-5p, miRNA-376b-5p, miRNA-383-5p) and one up-regulated microRNA (miRNA-195-3p) were found in rat peri-infarct with PH. Ten of these 14 PH-related microRNAs were significantly differentially expressed in at least two of five models of neuron, astrocyte, microglia, BMEC, and pericyte after OGD/R, consistent with the animal model results. Thirty-one predicted hub target genes were significantly differentially expressed in rat peri-infarct with PH. Forty-nine microRNA-mRNA regulatory axes of PH were revealed, which were related to the mechanisms of oxidative stress, apoptosis, immune, and inflammation. Simultaneously differentially expressed microRNAs and related genes in several cells of the neurovascular unit may serve as valuable targets for PH after endovascular thrombectomy in acute ischemic stroke.

neuroscience↗