Tumor Necrosis Factor-c* Expression in Ischemic Neurons

Background and Purpose Tumor necrosis factor-a (TNF-a) 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-a messenger RNA (mRNA) and peptide are expressed in the brain after experimental focal stroke and before leukocyte accumulation. Methods TNF-a mRNA and protein expression were monitored in the ischeraic and nonischemic cerebral cortex of rats after focal ischemia produced by permanent middle cerebral artery occlusion. The effect of TNF-a administered by microinjection into the brain cortex on leukocyte adherence to brain capillaries was also studied. Results Induction of TNF-a mRNA, normalized to a standard reference rat macrophage TNF-a mRNA, was detected as early as 1 hour after middle cerebral artery occlusion. TNF-a 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-a mRNA levels in ischemic cortex were still significantly elevated (38±5%; P<.05). Also, TNF-a mRNA expression was greater in the