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 microM) 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 glutamine antagonist kynurenate. In contrast, little protection could be obtained with gamma-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.
Monyer
H
H
Department of Neurology, Stanford Univeristy Medical Center, CA 94305.
Goldberg
M P
MP
Choi
D W
DW
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D000596:Amino Acids; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D015763:2-Amino-5-phosphonovalerate; D007770:L-Lactate Dehydrogenase; D014633:Valine; D005947:Glucose; C031231:2-amino-7-phosphonoheptanoic acid