Differential effects of anoxia and glutamate on cultured neocortical neurons.

That glutamate increases in the extracellular space of the brain during hypoxia or ischemia and that this amino acid, in high enough concentrations, kills neurons has led investigators to use glutamate and study the mechanisms underlying neuronal excitotoxicity as a model for acute cell death that occurs with low oxygen. However, there is some evidence that increased glutamate, on the one hand, and anoxia, on the other, may not be similar events. In this study we undertook experiments to determine whether glutamate, at various concentrations (20-500 microM), and anoxia induce similar changes in intracellular Ca2+ and in cell morphology as assessed by cell volume and eccentricity (degree of some ellipsoid shape). We found that glutamate was much more rapid in inducing a rise in Cai2+ and that the rise itself occurred at a faster rate than during anoxia. Anoxia produced more marked changes in cell volume and eccentricity. These results, which show major differences between glutamate and anoxia, indicate that while glutamate may play an important role in anoxic brain injury, glutamate excitotoxicity should not be used to mimic the effects of anoxia on nerve and brain function.