Differential expression profiles of circular RNAs in the rat hippocampus after deep hypothermic circulatory arrest

Abstract

Neurological dysfunction commonly occurs after cardiac surgery with deep hypothermic circulatory arrest (DHCA). The mechanisms underlying DHCA-associated brain injury remain poorly understood. This study determined the changes in expression profiles of circular RNAs (circRNAs) in the hippocampus in rats that underwent DHCA, with an attempt to explore the potential role of circRNAs in the brain injury associated with DHCA. Adult male Sprague Dawley rats were subjected to cardiopulmonary bypass with DHCA. Brain injury was evaluated by neurological severity scores and histological as well as transmission electron microscope examinations. The expression profiles of circRNAs in the hippocampal tissues were screened by microarray. Quantitative real-time PCR (RT-qPCR) was used to validate the reliability of the microarray results. Bioinformatic algorithms were applied to construct a competing endogenous RNA (ceRNA) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore the potential biological roles of the circRNAs. Out of 14 145 circRNAs screened, 56 were differentially expressed in the hippocampus between the DHCA and sham-operated rats, including 30 upregulated and 26 downregulated circRNAs. The expression changes of six selected circRNAs (upregulated: rno_cir-cRNA_011190, rno_circRNA_012988, rno_circRNA_000544; downregulated: rno_circRNA_010393, rno_circRNA_012043, rno_circRNA_015149) were further confirmed by RT-qPCR. Bioinformatics analysis showed the enrichment of these confirmed circRNAs and their potential target mRNAs in several KEGG pathways including histidine metabolism, adipocytokine signaling, and cAMP signaling. By revealing the change expression profiles of circRNAs in the brain after DHCA, this study indicates possible involvements of these dysregulated circRNAs in brain injury and suggests a potential of targeting circRNAs for prevention and treatment of neurological dysfunction associated with DHCA.

Transcriptomic Profiling of circRNAs in rat Hippocampus after Deep Hypothermic Circulatory Arrest

“…At present, a large number of studies have shown that circRNAs regulated ischemia-induced brain injury 15 , 26 . Our results confirmed that the expression profiles of circRNAs in rat hippocampus changed after the DHCA procedure, which was consistent with other studies 27 . However, the number of total circRNAs and dysregulated circRNAs in our results was far more than in the previous study 27 .…”

“…Our results confirmed that the expression profiles of circRNAs in rat hippocampus changed after the DHCA procedure, which was consistent with other studies 27 . However, the number of total circRNAs and dysregulated circRNAs in our results was far more than in the previous study 27 . Many reasons attribute to this difference, such as the differences in sequencing methods and experimental environments.…”

Cannabinoid Receptor Agonist WIN55, 212-2 Attenuates Injury in the Hippocampus of Rats after Deep Hypothermic Circulatory Arrest

“…A study in fetal lambs demonstrated that WIN 55, 212-2 reduces hypoxia/ischemia-induced apoptotic cell death in the brain through the maintenance of mitochondrial integrity and functionality [ 41 ]. In our previous study, we observed ultrastructure changes in mitochondria in the hippocampus of rats following DHCA, showing swelling, cavitation of the mitochondrial matrix, and loss of the mitochondrial cristae [ 26 ]. Whether WIN 55, 212-2 preserves mitochondrial integrity and functionality to improve neuronal survival in the hippocampus is, therefore, of interest for further studies.…”

“…The CPB and DHCA procedures were performed as described in our previous study [ 26 ] with slight modifications. Briefly, after fasting for 12 h, the animals were anesthetized with 2% isoflurane.…”

Construction and analysis of circular RNA-associated competing endogenous RNA network in the hippocampus of aged mice for the occurrence of postoperative cognitive dysfunction

“…MiR-190a, miRNA-181b-5p and miRNA-146a alleviated POCD by inhibiting hippocampal neuroinflammation ( Chen et al, 2019 ; Liu et al, 2019 ; Lu et al, 2019 ). Previous brain studies indicated that circRNAs played a unique role in the regulation of perioperative brain function through ceRNA networks ( Li et al, 2021 ). This study aimed to establish a perioperative circRNA-related ceRNA network in the hippocampus based on RNA sequencing (RNA-seq).…”