Glucose deprivation neuronal injury in cortical culture

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.