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Stroke, Vol 23, 1817-1821, Copyright © 1992 by American Heart Association

ARTICLES

Extracellular alkalinity exacerbates injury of cultured cortical neurons

RG Giffard, JH Weiss and DW Choi
Department of Anesthesia, Stanford University School of Medicine, Calif. 94305-5117.

BACKGROUND AND PURPOSE: We have previously shown that extracellular acidity protects cultured fetal murine neocortical neurons from glutamate toxicity and combined oxygen-glucose deprivation injury, an action at least in part mediated by reduction in N-methyl-D-aspartate receptor activation. We now investigate the effect of extracellular alkalinity on both glutamate neurotoxicity and injury due to combined oxygen-glucose deprivation. METHODS: The effects of extracellular alkalinity during injury induced by exposure of murine neocortical cultures to glutamate (0.5 mM for 5 minutes) or oxygen-glucose deprivation are characterized morphologically and quantitated by efflux of lactate dehydrogenase from both neurons and glia to the bathing medium. Calcium accumulation is measured with calcium-45. RESULTS: Moderate extracellular alkalinity is well tolerated by cortical cells but significantly potentiates both glutamate neuronal toxicity and oxygen-glucose deprivation neuronal injury. In contrast, glial viability in the face of combined oxygen-glucose deprivation is little affected by extracellular alkalinity. Increased accumulation of calcium- 45 during oxygen-glucose deprivation in alkalotic medium and blockade of this increase by MK-801 is demonstrated. CONCLUSIONS: These observations suggest that alkaline pH can exacerbate excitotoxic neuronal injury, most likely because of increased N-methyl-D-aspartate receptor activation. Metabolic alkalosis of any etiology may sensitize neurons to ischemic injury and potentiate reperfusion injury.

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