Activation of microglial cells and production of inflammatory factorscontribute to neuronal damage in various forms of brain injury. Previousstudies associated regulation of microglial activation with proliferativeand apoptotic processes. This study examined the temporal and spatialresponse of microglia within the framework of hippocampal neuronaldeath or survival. In young male CD-1 mice, selective damage of dentategyrus (DG) granule neurons was produced by an acute injection oftrimethyltin (TMT; 2 mg/kg, ip). Pyramidal CA neurons were notdamaged. QT-PCR of RNA from DG or CA cells, as collected by lasercapture microdissection, showed early elevations of TNF-alpha and theTNF-alpha receptors p55 and p75. The temporal pattern of increasedTNF-alpha and TNF-alpha receptor mRNA levels coincide withmorphological responses of activated microglia in the DG and reactivemicroglia in the CA layer. Proliferation, as determined by immuno-staining for BrdU and Ki-67, was predominantly localized to neuronalcells rather than in microglia. TUNEL and active caspase 3 immunoh-istochemistry for apoptotic cell death was evident in DG neurons. Datafrom this study suggest hippocampal microglia regulation via differen-tiation from a resting to phagocytic phenotype, rather than via cellproliferation and apoptotic cell death