Although neurotrophic factoros and cytokines were known to protect CNS neurons aginst hypoxic/ischemic insults, the mechanisms in their neuroprotective roles are unknown. We have investigated a role of ORP150, initially characterized based on its expression in astrocytes subjected to oxygen deprivation, in hypoxic neuronal cell death. Immunohistchemical and in situ hybridization studies showed the early and marked increase of ORP150 in neurons and astrocytes in ischemic regions of a rat MCA occlusion model, whereas exposure of cultured cortical neurons to hypoxia induced no increase in ORP150 protein level. However, incubation of the cultured neurons with TNFα, which was upregulated in MCA-occluded cerebral hemisphere and showed neuroprotectability in cultured neurons against hypoxic insult, induced 10-fold increase of the antigen, while incubation of either IGF-1, basic FGF or EGF was without effect. These data indicate that ORP150 may participate in neuroprotective role of TNFα in ischemic/hypoxic brain.