Diphenylhydantoin attenuates hypoxia-induced release of [3H]glutamate from rat hippocampal slices.

The ability of diphenylhydantoin (DPH) to prevent hypoxia-induced [3H]glutamate release was examined in perfused rat hippocampal slices. Hypoxia (25 min; 95% N2/5% CO2) caused a prolonged release of [3H]glutamate, which was reduced significantly if DPH (20 microM) was present from the beginning of the perfusion. Perfusion with oxygenated medium (reoxygenation) following hypoxia also caused a pronounced release of glutamate. A therapeutic concentration of DPH, added before, during, or after hypoxia, decreased this release of glutamate. These results suggest that DPH may protect against glutamate-mediated neurotoxicity associated with stroke.