Tumor necrosis factor-alpha. A mediator of focal ischemic brain injury

Stroke; a Journal of Cerebral Circulation
F C BaroneG Z Feuerstein

Abstract

Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine that rapidly upregulates in the brain after injury. The present study was designed to explore the pathophysiological significance of brain TNF-alpha in the ischemic brain by systematically evaluating the effects of lateral cerebroventricular administration of exogenous TNF-alpha and agents that block the effects of TNF-alpha on focal stroke and by examining the potential direct toxic effects of TNF-alpha on cultured neurons to better understand how TNF-alpha might mediate stroke injury. TNF-alpha (2.5 or 25 pmol) was administered intracerebroventricularly to spontaneously hypertensive rats 24 hours before permanent or transient (80 minutes and 160 minutes) middle cerebral artery occlusion (MCAO). Animals were examined 24 hours later for neurological deficits and ischemic hemisphere necrosis and swelling. In some of these studies, neutralizing anti-TNF-alpha monoclonal antibody (mAb) (60 pmol) was injected intracerebroventricularly 30 minutes before exogenous TNF-alpha (25 pmol). In addition, the effects of blocking endogenous TNF-alpha on permanent focal ischemic injury were determined with the use of either mAb (60 pmol) or soluble TNF receptor I (sTNF-RI) (0.3 ...Continue Reading

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