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)
Friedman
J E
JE
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520.
Haddad
G G
GG
D000818:Animals; D002118:Calcium / Q000378:metabolism; D048429:Cell Size / Q000502:physiology; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000473:pathology* / Q000503:physiopathology; D066298:In Vitro Techniques; D009474:Neurons / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000502:physiology*
D012964:Sodium; D002118:Calcium