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Science 4 June 1993:
Vol. 260. no. 5113, pp. 1516 - 1518
DOI: 10.1126/science.8389056
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Articles

Science, Vol 260, Issue 5113, 1516-1518
Copyright © 1993 by American Association for the Advancement of Science

articles

Neuroprotective effects of glutamate antagonists and extracellular acidity

DA Kaku, RG Giffard, and DW Choi

Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305.

Glutamate antagonists protect neurons from hypoxic injury both in vivo and in vitro, but in vitro studies have not been done under the acidic conditions typical of hypoxia-ischemia in vivo. Consistent with glutamate receptor antagonism, extracellular acidity reduced neuronal death in murine cortical cultures that were deprived of oxygen and glucose. Under these acid conditions, N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate-kainate antagonists further reduced neuronal death, such that some neurons tolerated prolonged oxygen and glucose deprivation almost as well as did astrocytes. Neuroprotection induced by this combination exceeded that induced by glutamate antagonists alone, suggesting that extracellular acidity has beneficial effects beyond the attenuation of ionotropic glutamate receptor activation.


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