J Korean Neurosurg Soc.  2011 Sep;50(3):173-178. 10.3340/jkns.2011.50.3.173.

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

• Chung JY
• Yi JW
• Kim SM
• Lim YJ
• Chung JH
• Jo DJ

• KMID: 1963604
• DOI: http://doi.org/10.3340/jkns.2011.50.3.173

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.

Keyword

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

MeSH Terms

Animals
Apoptosis
Brain
Brain Ischemia*
Energy Metabolism
Gene Expression*
Hippocampus*
Ischemia
Ischemic Attack, Transient
Middle Cerebral Artery
Oligonucleotide Array Sequence Analysis
Oxidative Phosphorylation
Rats*
Signal Transduction
Stroke