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)
Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520.
J E
JE
Friedman
G G
GG
Haddad
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