Abstract TP139: MicroRNAs Expression Patterns of Hemorrhagic Transformation After Mechanical Reperfusion for Acute Ischemic Stroke in Rat

Abstract

Background: Severe hemorrhagic transformation (HT) after mechanical thrombectomy and intravenous thrombolysis predicts poor clinical outcome in acute ischemic stroke. The specific roles of microRNAs in the pathogenesis of HT, however, are still unclear. Thus, the aim of this study is to investigate miRNA expression profiles in the rat ischemic brain with HT after mechanical reperfusion. Methods: A model of reperfusion-induced HT was established in rats with hyperglycemic challenge and 5h middle cerebral artery occlusion (MCAO) followed by 19h reperfusion. Infarct volume, brain water content, HT, neurological score, and blood-brain barrier damage were determined at 24h after cerebral ischemia. The miRNA expression profiling of rat brain samples in the MCAO group and those in the sham-operated group was performed using the miRCURYLNA Array. The differentially expressed miRNAs were further validated by qRT-PCR. Then, after predicting their target genes from top-ranked miRNAs, the KEGG and GO analyses were further used to predict the associated significant cell signaling pathways and functions. Results: Reperfusion with 5h of MCAO induced HT in all hyperglycemic rats, and most of them were the parenchymal hematoma. The results from the miRNA array revealed that 57 miRNAs were significantly altered 24h after reperfusion in the ischemic brain with HT. The expressions of these 57 miRNAs were further verified using qRT-PCR, and 33 top-ranked miRNAs were confirmed. Among them, 30 miRNAs were significantly downregulated and 3 were significantly upregulated in rats with HT. The top-listed downregulated miRNAs included miR-383-5p, miR-335, miR-376a-5p, miR-212-5p, miR-219a, miR-126a-5p. Three miRNAs were significantly upregulated, including miR-125b, miR-195, miR-214. The most enriched pathways are associated with the Hippo signaling pathway which regulates cell survival and death. Twenty significantly regulated miRNAs involve into the Hippo signaling pathway, including miR-383-5p. Conclusions: Alteration of the miRNAs in the ischemic brain with HT may serve as biomarkers for HT after mechanical reperfusion in acute ischemic stroke. The role of reperfusion-inducible miR-383-5p and Hippo signaling pathway in the HT requires further investigation.