Inhibition of TNF-alpha can attenuate or exacerbate excitotoxic injury in neonatal rat brain.
Tumor necrosis factor (TNF)-alpha, a multifunctional pro-inflammatory cytokine, 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 activity would reduce excitotoxic brain injury in neonatal rats. To test this hypothesis, we evaluated the efficacy of a TNF binding protein (bp) in attenuating NMDA-induced injury in 7 day old rats. Intrastriatal co-injection of TNFbp (3.75 microg) with NMDA (10 nmol) reduced striatal injury by 26%; in contrast, intra-hippocampal co-injection of TNFbp (3.75 microg) with NMDA (10 nmol) increased hippocampal damage by 68%. These findings indicate that TNF-alpha may have both beneficial and deleterious effects in the injured neonatal brain.
Galasso
J M
JM
Neuroscience Program, University of Michigan Medical Center, Ann Arbor 48109-0646, USA.
Wang
P
P
Martin
D
D
Silverstein
F S
FS
D000818:Animals; D000831:Animals, Newborn; D001284:Atrophy / Q000139:chemically induced; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D002352:Carrier Proteins / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004357:Drug Synergism; D018690:Excitatory Amino Acid Agonists; D006624:Hippocampus / Q000187:drug effects / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D007249:Inflammation; D016202:N-Methylaspartate; D009498:Neurotoxins; D051381:Rats; D017207:Rats, Sprague-Dawley; 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* / Q000378:metabolism*
D002352:Carrier Proteins; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; 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; D016202:N-Methylaspartate