Phenytoin protects against hypoxia-induced death of cultured hippocampal neurons.

The neuroprotective actions of the anticonvulsant phenytoin (diphenylhydantoin, PHT) were evaluated using 3 week old primary hippocampal cultures derived from 19 day embryonic rat. When added to the culture medium prior to a hypoxic insult, PHT increased neuronal viability two-fold. Doubling extracellular Mg2+ concentration was similarly neuroprotective. In contrast, PHT was unable to protect against hypoxia-induced death in one week old cultures, nor was PHT protective against N-methyl-D-aspartate (NMDA)-induced neurotoxicity in cultures of either age. These findings suggest that non-NMDA receptor mechanisms are important in hypoxia-induced neuronal death, and may have important implications for the treatment of stroke.