Analysis of microRNA expression in cerebral ischemia/reperfusion after mild therapeutic hypothermia treatment in rats

Shangfeng Zhao; Xiangrong Liu; Jun Kang; Si Sun; Yong Li; Jialiang Zhang; Qi Li; Xunming Ji

doi:10.21037/atm-21-143

Analysis of microRNA expression in cerebral ischemia/reperfusion after mild therapeutic hypothermia treatment in rats

Ann Transl Med. 2021 Jan;9(2):168. doi: 10.21037/atm-21-143.

Authors

Shangfeng Zhao¹, Xiangrong Liu², Jun Kang¹, Si Sun¹, Yong Li¹, Jialiang Zhang¹, Qi Li², Xunming Ji³

Affiliations

¹ Department of Neurosurgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China.
² China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
³ Department of Neurosurgery, Xuanwu Hospital of Capital Medical University, Beijing, China.

Abstract

Background: This study aimed to explore the molecular mechanism of mild hypothermia in in the treatment of cerebral ischemia, microRNA (miRNA) microarrays and bioinformatics analysis were employed to examine the miRNA expression profiles of rats with mild therapeutic hypothermia after middle cerebral artery occlusion (MCAO).

Methods: MCAO was induced in Male Sprague-Dawley rats. Mild hypothermia treatment began from the onset of ischemia and maintained for 3 hours. miRNA expressions following focal cerebral ischemia and mild hypothermia treatment were profiled using microarray technology. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the functions of the target genes in mild therapeutic hypothermia after MCAO. 60 min before MCAO, mimics and inhibitor of miR-291b were injected into the right lateral ventricle respectively, then the infarct volume and neuronal apoptosis were analyzed.

Results: Six upregulated miRNAs and 6 downregulated miRNAs were detected 4 hours after mild therapeutic hypothermia, and after 24 hours, 41 and 10 miRNAs were upregulated and downregulated, respectively. The target genes of the differentially expressed genes were mainly related with multicellular organism development and the mucin type O-glycan biosynthesis pathway was the most enriched KEGG pathway. Among the differentially expressed miRNAs, miR-291b was selected to assess the effects of mild therapeutic hypothermia in MCAO rats. At 24 hours after mild therapeutic hypothermia, miR-291b overexpression was proved to exhibit neuroprotective effects.

Conclusions: The results showed that miRNAs might play a pivotal role in mild therapeutic hypothermia in cerebral ischemia/reperfusion injury. Further understanding of the mechanism and function of miRNAs would help to illuminate the mechanism of mild therapeutic hypothermia in cerebral ischemia/reperfusion injury.

Keywords: Cerebral ischemia/reperfusion; Gene Ontology (GO); KEGG pathway; miR-291b; microRNA expression (miRNA expression); microRNA microarray (miRNA microarray); mild therapeutic hypothermia.