INHIBITION OF TUMOR-NECROSIS-FACTOR AND AMELIORATION OF BRAIN INFARCTION IN MICE

Tumor necrosis factor alpha (TNF-alpha) is expressed in the ischemic b rain; however, its precise role is not fully understood. We studied th e effect of the dimeric form of the type I soluble TNF receptor linked to polyethylene glycol (TNFbp) on focal cerebral ischemia in mice usi ng a permanent middle cerebral arterial occlusion (MCAO) model. TNFbp was applied topically, intravenously, or intraperitoneally. TNFbp bind s and inhibits TNF-alpha. The volume of cortical ischemic lesions was measured by means of 2,3,5-triphenyltetrazolium chloride 24 h after MC AO. TNFbp produced a significant reduction in the cortical infarct vol ume of vehicle-treated animals (p < 0.001). The reduction in the volum e of brain damage was 26% in animals that received 3 mg/kg of TNFbp to pically. Further analysis of TNF-alpha inhibition following acute brai n ischemia is indicated.