Delayed production of nitric oxide contributes to NMDA-mediated neuronal damage

Exposure of primary murine cortical neuron cultures to N-methyl-D-aspartate (NMDA) resulted in neuronal death as evidenced by release of lactate dehydrogenase (LDH) into the media. The addition of N-nitro-L-arginine (N-Arg) protected the neurons from death in a concentration-dependent manner when added after the NMDA, but not when the N-Arg was present with the NMDA. Protection by N-Arg was lost if L-arginine containing media was added to the cultures prior to the addition of the N-Arg. Treatment of the neurons with kainate prior to NMDA reduced subsequent NMDA-induced damage which was not prevented with N-Arg. These results suggest that delayed production of nitric oxide (NO) contributes to NMDA-induced neuronal damage in culture.