Removal of extracellular sodium prevents anoxia-induced injury in freshly dissociated rat CA1 hippocampal neurons.

Anoxia is believed to cause nerve injury and death in part, by inducing sustained, elevated levels of intracellular Ca2+. The increased concentration of intracellular Ca2+ is capable, by itself, of inducing nerve injury and death, even without the added stress of anoxia. However, we have recently shown that an increased level of intracellular Ca2+ is not necessary for anoxia-induced CA1 nerve injury. Since we have observed that extracellular Na+ decreases during anoxia, we studied the role of extracellular Na+ in anoxia-induced nerve injury. Removal of extracellular Na+ and its replacement with the impermeant cation N-methyl-D-glucamine (NMDG+) completely protected freshly dissociated CA1 neurons during and after severe anoxia, for up to 90 min. Intracellular Ca2+ decreased during anoxia, recovering during reoxygenation. Propidium iodide was excluded from the neurons for as long as Na+ was absent. Addition of Na+ (by replacing NMDG+) following anoxia resulted in rapid bleb formation, swelling and intracellular Ca2+ rise. Removal of Na+ before the rupture of blebs caused either shrinkage or pinching off of blebs so that the neuron apparently returned to its previous undisturbed state.(ABSTRACT TRUNCATED AT 250 WORDS)