DNA microarray analysis of cortical gene expression during early recirculation after focal brain ischemia in rat

Focal brain ischemia is followed by changes in gene expression as reflected by altered mRNA levels. DNA microarray analysis can be used to survey thousands of genes for differential expression triggered by ischemic metabolic stress. In this study, Sprague-Dawley rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) using an intravascular poly-L-lysine-coated filament, and brains were removed after 3 h of recirculation for mRNA isolation. A differential measurement of mRNAs from post-ischemic and sham control animals was performed using the Mouse UniGene I microarray. Established values for differential expression were used (greater than or equal to1.7 or less than or equal to-1.7 fold), and hits (n=2-3 arrays) divided into known 'ischemia-hypoxia response' genes and 'newly connected' annotated genes. n=28 ischemia-hypoxia response genes were up-regulated and n=6 were down-regulated. Regulated genes comprised immediate early genes, heat-shock proteins, anti-oxidative enzymes, trophic factors, and genes involved in RNA metabolism, inflammation and cell signaling. Based on the ability of the microarray to replicate known changes in gene expression, n=35 newly connected genes were found up-regulated and n=41 down-regulated. DNA microarray analysis allows one to develop novel working hypotheses for responses to brain ischemia based on the regulation of annotated genes. (C) 2002 Elsevier Science B.V. All rights reserved.