Possible mechanisms limiting N-methyl-D-aspartate receptor overactivation and the therapeutic efficacy of N-methyl-D-aspartate antagonists.
Cytotoxic overactivation of neuronal N-methyl-D-aspartate receptors is postulated to contribute to the pathogenesis of neuronal loss in hypoxia-ischemia. However, several events associated with hypoxia-ischemia may limit N-methyl-D-aspartate receptor-mediated injury. Perhaps the most important of these events is the development of extracellular acidosis. These limiting events may help explain why N-methyl-D-aspartate receptors contribute to injury more in focal ischemia or hypoxia in vitro than in global ischemia.
Choi
D W
DW
Department of Neurology, Stanford University Medical Center, Calif. 94305.
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000378:metabolism*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D015032:Zinc; D000241:Adenosine; D002118:Calcium