PT  - JOURNAL ARTICLE
AU  - M P Goldberg
AU  - J H Weiss
AU  - P C Pham
AU  - D W Choi
TI  - N-methyl-D-aspartate receptors mediate hypoxic neuronal injury in cortical culture.
DP  - 1987 Nov 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 784--791
VI  - 243
IP  - 2
4099  - http://jpet.aspetjournals.org/content/243/2/784.short
4100  - http://jpet.aspetjournals.org/content/243/2/784.full
SO  - J Pharmacol Exp Ther1987 Nov 01; 243
AB  - The ability of several glutamate receptor antagonists to reduce hypoxic cortical neuronal injury was quantitatively examined in cell cultures derived from fetal mice. Cultures exposed to hypoxia for 8 hr showed by the following day widespread neuronal injury, which was substantially attenuated by addition of the specific N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (APV). The protective effect of APV was concentration dependent (ED50 about 2 microM) and stereospecific (D-APV approximately 100 times more potent that L-APV). Neuron-protective effects were also observed with several other NMDA antagonists: 2-amino-7-phosphonoheptanoate, phencyclidine and (+)-SKF 10,047 [(+)-N-allylnormetazocine]--as well as with the nonspecific glutamate antagonists D-glutamylglycine and kynurenate. In addition, a similar antagonist profile was observed with a chemical model of hypoxic neuronal injury, produced by brief exposure to high concentrations of cyanide. In contrast, 1 mM concentrations of glutamate diethylester and gamma-aminomethyl sulfonate, compounds reported in some studies to preferentially antagonize non-NMDA glutamate receptors, failed to protect neurons against either hypoxia or cyanide. These results are consistent with the hypothesis that NMDA receptors are preferentially involved in the pathogenesis of hypoxic cortical neuronal injury and suggest that cortical cell culture may be a useful system in which to quantitatively characterize the pharmacology of that injury.