THE EFFECT OF MAGNESIUM ON OXIDATIVE NEURONAL INJURY IN-VITRO

The effect of magnesium on the oxidative neuronal injury induced by he moglobin was assessed in murine cortical cell cultures. Exposure to 5 mu M hemoglobin in physiologic (1 mM) magnesium for 26 h resulted in t he death of about one-half the neurons and a sixfold increase in malon dialdehyde production; glia were not injured. Increasing medium magnes ium to 3 mM reduced neuronal death by about one-half and malondialdehy de production by about two-thirds; neuronal death and lipid peroxidati on were approximately doubled in 0.3 mM magnesium, Comparable results were observed in spinal cord cultures. The NMDA antagonist MK-801 weak ly attenuated hemoglobin neurotoxicity in low-magnesium medium, but te nded to potentiate injury in physiologic magnesium. Incubation in low- magnesium medium alone for 24 h reduced cellular glutathione by simila r to 50% in mixed neuronal and glial cultures but by only 10% in pure glial cultures. The iron-dependent oxidation of phosphatidylethanolami ne liposomes was attenuated in a concentration-dependent fashion by 2. 5-10 mM magnesium; a similar effect was provided by 0.01-0.1 mM cobalt . However, oxidation was weakly enhanced by 0.5-1 mM magnesium. These results suggest that the vulnerability of neurons to iron-dependent ox idative injury is an inverse function of the extracellular magnesium c oncentration. At high concentrations, magnesium inhibits lipid peroxid ation directly, perhaps by competing with iron for phospholipid bindin g sites. At low concentrations, enhancement of cell death may be due t o the combined effect of increased NMDA receptor activity, glutathione depletion, and direct potentiation of lipid peroxidation.