Tumor necrosis factor-α expression in ischemic neurons

Abstract

Background and PurposeTumor necrosis factor-a (TNF-α) is a cytokine with diverse proinflammatory actions, including endothelial leukocyte adhesion molecule expression. Since leukocytes infiltrate into ischemic brain lesions, the present study was conducted to examine whether TNF-α messenger RNA (mRNA) and peptide are expressed in the brain after experimental focal stroke and before leukocyte accumulation. MethodsTNF-α mRNA and protein expression were monitored in the ischemic and nonischemic cerebral cortex of rats after focal ischemia produced by permanent middle cerebral artery occlusion. The effect of TNF-α administered by micro-injection into the brain cortex on leukocyte adherence to brain capillaries was also studied. ResultsInduction of TNF-α mRNA, normalized to a standard reference rat macrophage TNF-α mRNA, was detected as early as 1 hour after middle cerebral artery occlusion. TNF-α mRNA was elevated by 3 hours (29±6% versus 2±1% in sham-operated rats) only in the ischemic cortex, with peak expression at 12 hours (104±8%;P<01). Five days after middle cerebral artery occlusion, TNF-α mRNA levels in ischemic cortex were still significantly elevated (38±5%; P