NEUROPROTECTIVE EFFECTS OF TNF BINDING-PROTEIN IN FOCAL CEREBRAL-ISCHEMIA

The effect of tumor necrosis factor binding protein (TFNbp) was studie d in mice subjected to a permanent middle cerebral artery occlusion (M CAO). TNFbp is a dimeric form of the type I soluble TNF receptor linke d to polyethylene glycol (TNFbp), and binds and inhibits TNF-alpha. TN Fbp produced a significant reduction in the cortical infarct volume (2 2.6 +/- 3.5 mm(3) immediately after MCAO; 25.2 +/- 2.4 mm(3) 1 h after MCAO) compared with vehicle-treated animals (30.3 +/- 3.7 mm(3) immed iately post MCAO; 31 +/- 3.7 mm(3) 1 h after MCAO (mean +/- S.D.) when administered intracranially up to 60 min post-occlusion. The neuropro tective effect of TNFbp was sustained in mice for 2 weeks after MCAO. DNA fragmentation at the margin of the cortical infarcts was dramatica lly reduced in mice treated with TNFbp whereas all control animals sho wed consistent and obvious DNA fragmentation 2 weeks after MCAO. TNFbp could have therapeutic value for the treatment of ischemic stroke if the problem of delivery to brain can be overcome. (C) 1997 Elsevier Sc ience B.V.