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

Chung, Jun Young; Yi, Jae Woo; Kim, Sung Min; Lim, Young Jin; Chung, Joo Ho; Jo, Dae Jean

doi:2011.50.3.173

Original Article

Journal of Korean Neurosurgical Society 2011;50(3): 173-178.
doi: https://doi.org/10.3340/jkns.2011.50.3.173

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

Jun Young Chung, Jae Woo Yi, Sung Min Kim, Young Jin Lim, Joo Ho Chung, Dae Jean Jo

¹Department of Anesthesiology, College of Medicine, Kyung Hee University, Seoul, Korea.
²Department of Neurosurgery, College of Medicine, Kyung Hee University, Seoul, Korea. apuzzo@hanmail.net
³Department of Pharmacology, College of Medicine, Kyung Hee University, Seoul, Korea.

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.

Key Words: Apoptosis; Energy metabolism; Focal cerebral ischemia; Gene expression; Hippocampus; Oxidative phosphorylation