A number of factors influence the pattern of neuronal death following acutebrain injury including contact with glial cells and response to an inflamma-tory environment. Injury-induced generation of progenitor cells and theirmaturation to neurons can occur in an inflammatory environment. In thecurrent study we examined the cellular expression of tumor necrosis factorreceptors (TNFR) in neurons in contact with either microglia or astrocytes inthe framework of neuronal death or survival. Selective damage to dentategranuleneuronswasproducedbyanacuteinjectionoftrimethyltin(2 mg/kg,ip)to young CD-1 male mice. Dentate granule cell death occurring within 6 h ofinjection was characterized by a cytoplasmic staining for TNFR p55, stainingfor active caspase 3, and cell contact with lectin+ activated microglia cells.By 72 h the majority of granule neurons died and the distribution of TNFRp55 in active caspase 3+ neurons appeared to have translocated to themembrane, while the neuron maintained contact with an activated microgliacell. During this same period neuronal survival was characterized by positivestaining for TNFR p75 and contact with astrocyte processes. BrdU+ cellswere rapidly induced following injury and primarily co-localized withneuronal markers. Neuronal maturation was associated with a temporalexpression of TNFR p55 and p75 and relationship with microglia andastrocytes. These results suggest the importance of the interaction betweenthe cellular expression and localization of TNF receptors and glia contact indetermining neuronal fate in response to brain injury.