Inhibition of tumor necrosis factor and amelioration of brain infarction in mice.
Tumor necrosis factor alpha (TNF-alpha) is expressed in the ischemic brain; however, its precise role is not fully understood. We studied the effect of the dimeric form of the type I soluble TNF receptor linked to polyethylene glycol (TNFbp) on focal cerebral ischemia in mice using a permanent middle cerebral arterial occlusion (MCAO) model. TNFbp was applied topically, intravenously, or intraperitoneally. TNFbp binds and inhibits TNF-alpha. The volume of cortical ischemic lesions was measured by means of 2,3,5-triphenyltetrazolium chloride 24 h after MCAO. TNFbp produced a significant reduction in the cortical infarct volume of vehicle-treated animals (p < 0.001). The reduction in the volume of brain damage was 26% in animals that received 3 mg/kg of TNFbp topically. Further analysis of TNF-alpha inhibition following acute brain ischemia is indicated.
Nawashiro
H
H
Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4128, USA.
Martin
D
D
Hallenbeck
J M
JM
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002545:Brain Ischemia / Q000150:complications; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000502:physiology
D018696:Neuroprotective Agents; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C069521:recombinant human tumor necrosis factor-binding protein-1