DNA array reveals altered gene expression in response to focal cerebral ischemia.

ABSTRACT

The gene expression profile in the cortex was analyzed in a rat model of focal cerebral ischemia by use of cDNA array. It was attempted to monitor changes of gene expression and to profile them into functional classification between ipsilateral and contralateral cortex at 6h after middle cerebral artery (MCA) occlusion. Seventy-one genes out of 1174 genes were significantly modulated by ischemia. Metabolism-, cell communication- and signal transduction-related genes were down-regulated, whereas genes involved in stress response were markedly increased. Besides numerous established ischemia-induced gene products such as macrophage inflammatory protein-1 alpha (MIP-1 alpha), orphan nuclear receptor Nurr 77, secretogranin II (SCG-II), and tumor necrosis factor-alpha (TNF-alpha), several genes were identified which have not previously been shown to be modulated following focal ischemia; these genes include interferon-induced protein (IFN-IP), neurodegeneration-associated protein-1 (NDGAP-1), and neuronal pentraxin receptor (NPR). The RT-PCR analyses of these genes at various time points revealed that mRNA level of IFN-IP was up-regulated, while NDGAP-1 and NPR were transcriptionally down-regulated. The results suggest of the involvement of these genes in neuronal cell damage caused by ischemia and the potential use as targets for the development of preventives/therapeutics of brain stroke.