High-density DNA microarray analysis of gene expression following transient focal cerebral ischemia in mouse

Cerebral ischemia induces active neuronal death, a process requiring energy and activation of cell death genes. The identification of genes involved in neuronal death process and postischemic injury repair is important in the development of mechanism-based therapies. To this end, we profiled gene expression in mouse brains, which were subjected to 2-h middle cerebral artery occlusion (MCAO) followed by 6-h reperfusion using high-density DNA microarrays. The DNA microarray contained cDNAs representing about 4000 sequence-verified, “brain-relevant” genes. The present study showed that the expression of about 10% of the genes on the array changed more than fivefolds, with about 5% up and 5% down. The identities of the genes revealed that cerebral ischemia induced the expression of death genes and decreased survival genes. The up-regulated detrimental genes include inflammatory genes, apoptosis genes and DNA damage responsive genes which acted as indicators for DNA damage. The down-regulated survival genes were genes encoding for antioxidants and factors critical for general transcription and translation machinery. Semiquantitative RT-PCR was used to verify the expression of selected genes, including caspases-8, cyclin D1 and profilin. The present study has led us to identify several potential target genes for further investigation.