Abstract
Murine cortical cell cultures deprived of glucose for 6-8 h developed extensive neuronal degeneration, apparent both morphologically and by efflux of lactate dehydrogenase to the bathing medium. This neuronal damage could be substantially reduced by addition of d-2-amino-5-phosphonovalerate (d-APV), in a concentration-dependent (IC50 about 2 μM) and stereospecific (d-APV more potent than l-APV) fashion. A similar neuron-protective effect could also be obtained with several other NMDA antagonists, 2-amino-7-phosphonoheptanoate, phencyclidine, MK-801, ketamine, and (+)-SKF 10,047, as well as with the broad spectrum glutamate antagonist kynurenate. In contrast, little protection could be obtained with γ-d-glutamylaminomethyl sulfonate and l-glutamate diethyl ester, compounds which have been reported to act primarily at non-NMDA receptors. These observations support the hypothesis that glucose deprivation-induced cortical neuronal injury is largely mediated by NMDA receptors, and suggest that cell culture methodology can be useful in the quantitative characterization of that injury.
Original language | English (US) |
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Pages (from-to) | 347-354 |
Number of pages | 8 |
Journal | Brain Research |
Volume | 483 |
Issue number | 2 |
DOIs | |
State | Published - Apr 3 1989 |
Keywords
- Asparatate
- Cell culture
- Cortex
- Excitatory amino acid
- Glutamate
- N-Methyl-d-aspartate receptor
- Neurotoxicity
ASJC Scopus subject areas
- General Neuroscience
- Molecular Biology
- Clinical Neurology
- Developmental Biology