Inhibition of TNF-alpha can attenuate or exacerbate excitotoxic injury in neonatal rat brain

Tumor necrosis factor (TNF)-alpha, a multifunctional pro-inflammatory cytok ine, has been implicated in the pathogenesis of acute ischemic brain injury . Recent data also suggest that TNF-alpha is a clinically relevant mediator of neonatal brain injury. We hypothesized that inhibition of TNF-alpha act ivity would reduce excitotoxic brain injury in neonatal rats. To test this hypothesis, we evaluated the efficacy of a TNF binding protein (bp) in atte nuating NMDA-induced injury in 7 day old rats. Intrastriatal co-injection o f TNFbp (3.75 mu g) with NMDA (10 nmol) reduced striatal injury by 26%; in contrast, intra-hippocampal co-injection of TNFbp (3.75 mu g) with NMDA (10 nmol) increased hippocampal damage by 68%. These findings indicate that TN F-alpha may have both beneficial and deleterious effects in the injured neo natal brain. NeuroReport 11:231-235 (C) 2000 Lippincott Williams & Wilkins.