Circular RNA Expression Profiles Are Significantly Altered after Cerebral Ischemia‒Reperfusion Injury in Different Parts of the Rat Brain

Purpose: The objective of this study was to investigate the connection between circular RNA (circRNA) and ischemia-reperfusion (I/R) injury set on by middle cerebral artery occlusion (MCAO) in different parts of the rat brain. Methods Using the MCAO technique, the adult male Sprague-Dawley rat model was created. At 24 hours after reperfusion, circRNA sequencing and real-time PCR were used to assess the circRNA expression profile in the ischemic region of the right cortex, striatum, and hippocampus. A bioinformatics investigation of the changed circRNAs following I/R injury was carried out, including the discovery of miRNA binding sites, analysis of transcription factor binding, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Ontology (GO) analysis. Results 85, 113 and 51 circRNAs in the cortex, striatum and hippocampus, respectively, substantially altered (|log2 (fold change)| > 1 and P < 0.05) after I/R, compared with the sham group. Significantly changed circRNAs found by sequencing analysis were confirmed by real-time PCR. Target genes of dysregulated circRNAs were connected to cellular components, biological processes, and molecular functions after I/R, according to GO and KEGG pathway studies. Finally, we successfully predicted a circMapk9-miR-29a-5p-gene network connected with NLRP3-mediated neuroinflammation in I/R. Conclusion The findings of this work provide the first investigation into the association between circRNAs and I/R injury brought on by MCAO in different parts of the rat brain, as well as a novel molecular target for the therapeutic management of I/R injury following endovascular thrombectomy (EVT).