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Previous Article | Next Article
The Journal of Neuroscience, March 1, 1999, 19(5):1657-1662
Ischemic Tolerance in Murine Cortical Cell Culture: Critical Role for NMDA Receptors
Margaret C. Grabb and Dennis W. Choi Center for the Study of Nervous System Injury and Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110
Murine cortical cultures containing both neurons and glia (days in vitro 13-15) were exposed to periods of oxygen-glucose deprivation (5-30 min) too brief to induce neuronal death. Cultures "preconditioned" by sublethal oxygen-glucose deprivation exhibited 30-50% less neuronal death than controls when exposed to a 45-55 min period of oxygen-glucose deprivation 24 hr later. This preconditioning-induced neuroprotection was specific in that neuronal death induced by exposure to excitotoxins or to staurosporine was not attenuated. Neuroprotection was lost if the time between the preconditioning and severe insult were decreased to 7 hr or increased to 72 hr and was blocked if the NMDA antagonist 100 µM 3-((D)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid was applied during the preconditioning insult. This was true even if the duration of preconditioning was increased as far as possible (while still remaining sublethal). A similar preconditioning effect was also produced by sublethal exposure to high K+, glutamate, or NMDA but not to kainate or trans-1-aminocyclopentane-1,3-dicarboxylic acid.
Key words: glutamate; cerebral preconditioning; NMDA; kainate; metabotropic; ischemia
Copyright © 1999 Society for Neuroscience 0270-6474/99/1951657-06$05.00/0
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