Abstract
The present study aimed to explore the potential mechanism of the effect of hyperbaric oxygenation (HBO) preconditioning on cerebral ischemia and reperfusion injury (CIRI). GSE23160 dataset was used to identify differentially expressed genes (DEGs) from striatum between the middle cerebral artery occlusion (MCAO)/reperfusion and sham rats. The gene clusters with continuous increase and decrease were identified by soft clustering analysis in Mfuzz, and functional enrichment analysis of these genes was performed using clusterProfiler package. The intersection set of the genes with significantly altered expression at post-reperfusion 2, 8, and 24 h were screened in comparison to 0 h (sham group), and the expression of these genes was detected in the MCAO/reperfusion model and HBO preconditioning groups by real-time PCR (RT-PCR) and western blotting. A total of 41 upregulated DEGs, and 7 downregulated DEGs were detected, among which the expression of Gpr84 and Ggta1 was significantly upregulated at each reperfusion phase as compared to the sham group, while the expression of Kcnk3 was significantly downregulated except in the postreperfusion 8 h in the striatum group. RT-PCR and western blotting analyses showed that the expression of Ggta1, Gpr84, and Kcnk3 genes between the MCAO/reperfusion and sham rats were consistent with the bioinformatics analysis. In addition, the HBO preconditioning reduced the expression of Ggta1 and Gpr84 and increased the expression of Kcnk3 in MCAO/reperfusion rats. Kcnk3, Ggta1, and Gpr84 may play a major role in HBO-mediated protection of the brain against CIRI.
Highlights
Stroke is one of the three major diseases that threaten human health, and the second-leading cause of death globally (Gorelick 2019)
In keeping with the real-time PCR (RT-PCR) analysis, the data of western blotting revealed that the protein level of G-protein-coupled receptor 84 (Gpr84) in middle cerebral artery occlusion (MCAO)/reperfusion rats was significantly upregulated in comparison to that in sham controls (P < 0.01; Fig. 6B); hyperbaric oxygenation (HBO) preconditioning could significantly suppress the expression of Gpr84 protein in MCAO/reperfusion rats (P < 0.01)
A set of 41 overlapped upregulated differentially expressed genes (DEGs) and 7 overlapped downregulated DEGs was found in the cortex and striatum groups, among which the upregulated expression of Gpr84 and Ggta1 was significantly different at each reperfusion time points in both groups, while that of downregulated Kcnk3 was distinct
Summary
Stroke is one of the three major diseases that threaten human health, and the second-leading cause of death globally (Gorelick 2019). Cerebral ischemia and reperfusion (I/R) injury (CIRI) following stroke aggravates brain damage when blood supply is restored (Venkat et al 2017). Since CIRI is one of the major causes of lethality, the prevention and alleviation of CIRI constitute the key processes for stroke research. Experimental Brain Research electroacupuncture (Huang et al 2019) and hyperbaric oxygenation (HBO) preconditioning (Hentia et al 2018) are currently applied to alleviate CIRI.
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