Effects of glutamate, quisqualate, and N-methyl-D-aspartate in neonatal brain

The intracerebral injection of the excitotoxins, glutamate (GLU), or its analogues, quisqualic acid (QA) and N-methyl-D-aspartate (NMDA), produces neuropathologic changes which resemble those induced by hypoxic-ischemic injury. We employed proton magnetic resonance spectroscopy to investigate the acute biochemical changes which follow injection of these excitotoxins in the neonatal rat brain. Aspartate and GLU increased in animals injected with GLU or NMDA. Alanine, glycine, and taurine increased with all three excitotoxins. There was no decrease in phosphocreatine (PCr) or glucose and only a modest increase in lactate after excitotoxin injection, but there was substantial change in these metabolites after hypoxia. GABA rose only after hypoxic-ischemic injury. Although NMDA and QA produced morphological changes which resembled those following hypoxic-ischemic injury, the effect of these excitotoxins on levels of PCr, glucose, and excitatory and inhibitory amino acids was considerably different.