Changes in Gene Expression in the Rat Hippocampus after Focal Cerebral Ischemia

Abstract

Objective : The rat middle cerebral artery thread-occlusion model has been widely used to investigate the pathophysiological mechanisms of stroke and to develop therapeutic treatment. This study was conducted to analyze energy metabolism, apoptotic signal pathways, and genetic changes in the hippocampus of the ischemic rat brain. Methods : Focal transient cerebral ischemia was induced by obstructing the middle cerebral artery for two hours. After 24 hours, the induction of ischemia was confirmed by the measurement of infarct size using 2,3,5-triphenyltetrazolium chloride staining. A cDNA microarray assay was performed after isolating the hippocampus, and was used to examine changes in genetic expression patterns. Results : According to the cDNA microarray analysis, a total of 1,882 and 2,237 genes showed more than a 2-fold increase and more than a 2-fold decrease, respectively. When the genes were classified according to signal pathways, genes related with oxidative phosphorylation were found most frequently. There are several apoptotic genes that are known to be expressed during ischemic brain damage, including Akt2 and Tnfrsf1a. In this study, the expression of these genes was observed to increase by more than 2-fold. As energy metabolism related genes grew, ischemic brain damage was affected, and the expression of important genes related to apoptosis was increased/decreased. Conclusion : Our analysis revealed a significant change in the expression of energy metabolism related genes (Atp6v0d1, Atp5g2, etc.) in the hippocampus of the ischemic rat brain. Based on this data, we feel these genes have the potential to be target genes used for the development of therapeutic agents for ischemic stroke.

Identifying the Involvement of Pro-Inflammatory Signal in Hippocampal Gene Expression Changes after Experimental Ischemia: Transcriptome-Wide Analysis

“…In our study, expression of TNF receptors upregulated in the hippocampus after both LPS and MCAO included Tnfrsf1a, Tnfrsf12a, and Tnfrsf26. The increase in Tnfrsf1a expression in the hippocampus of rats 24 h after ischemia was reported previously [11], and our data support this result. GO BP terms "inflammatory response", "response to lipopolysaccharide", and "regulation of cell proliferation" were mainly enriched with LPS-responding genes, including Tnfrsf1a and Tnfrsf26, and the numbers of these LPS-responding genes were 10 (Ccl2, Cd14, Hck, Tnfrsf1a, Anxa1, Casp4, Spp1, S1pr3, Thbs1, Tnfrsf26) from 17, 11 (Ccl2, Cd14, Fos, Tnfrsf1a, Csf2rb, Lbp, Ptges, Serpine1, Socs3, Trib1, Tnfrsf26) from 15, and 9 (Fgr, Hck, S100a11, Tnfrsf1a, Anxa1, B4galt1, Irf1, Serpine1, Tnfrsf26) from 11, accordingly.…”

Pathological Comparisons of the Hippocampal Changes in the Transient and Permanent Middle Cerebral Artery Occlusion Rat Models

“…Several studies confirmed apoptotic cell death in hippocampus after 24 h of ischemia in different rat strain (15, 41, 42). Our results are parallel to previous published reports, found apoptotic cell death in hippocampus after 24 h of ischemia (41, 43). Moreover, these authors found no changes in Caspase and Bcl-2 expression in hippocampus using I/R model.…”

Linking epigenetic signature and metabolic phenotype in IDH mutant and IDH wildtype diffuse glioma

“…Another study found that ATP5G2 was upregulated in an ischaemic rat brain model. The authors described upregulated ATP5G2 gene expression 24 h after artery occlusion [44], suggesting that ATP5G2 gene expression is an early hypoxia/ischaemia response gene. The role of the expression of genes like ATP5G2 in gliomas needs further investigation.…”

“…Another study found that ATP5G2 was upregulated in an ischaemic rat brain model. The authors described upregulated ATP5G2 gene expression 24 h after artery occlusion [44],…”