Neurotoxicity of N-methyl-D-aspartate is markedly enhanced in developing rat central nervous system

The neurotoxic lesion produced by direct injection of 25 nmol of N-methyl-D-aspartate (NMDA) into the corpus striatum of 7-day-old rats was compared to the effects of injecting 75 nmol into the striatum or hippocampus of adults. The area of histopathology in the immature striatum was 21 X larger than the striatal lesion in adults. Damage from NMDA injected into the immature striatum also extended into the dorsal hippocampus and produced an area of destruction which was 16 X larger than observed after direct injection into the adult hippocampus. Several studies have implicated excessive N-methyl-D-aspartate receptor activation in the pathogenesis of hypoxic-ischemic and hypoglycemic injury and our results suggest that this neurotoxic mechanism is extremely active in the immature brain.