title: Acidosis reduces NMDA receptor activation, glutamate neurotoxicity, and oxygen-glucose deprivation neuronal injury in cortical cultures.
abstract: The acidosis which accompanies cerebral ischemia in vivo has been thought to contribute to subsequent neuronal injury. However, recent electrophysiological recordings from hippocampal neurons suggest that H+ can attenuate N-methyl-D-aspartate (NMDA) receptor-mediated cation influx, likely a key event in the pathogenesis of ischemic neuronal injury. Here we report that moderate extracellular acidosis (pH 6.5) markedly reduced the inward whole cell current induced by NMDA on cultured cortical neurons; at pH 6.1, kainate-induced current was additionally reduced. Furthermore, such acidosis reduced the cortical neuronal injury caused by toxic glutamate exposure, as well as the neuronal degeneration and accumulation of 45Ca2+ induced by combined oxygen and glucose deprivation. These findings raise the possibility that moderate acidosis may decrease cortical neuronal vulnerability to ischemic damage.
authors.affiliation: Department of Anesthesia, Stanford University Medical center, CA 94305.
authors.forename: R G
authors.initials: RG
authors.lastname: Giffard
authors.forename: H
authors.initials: H
authors.lastname: Monyer
authors.forename: C W
authors.initials: CW
authors.lastname: Christine
authors.forename: D W
authors.initials: DW
authors.lastname: Choi
mesh_terms: D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004622:Embryo, Mammalian; D005947:Glucose / Q000378:metabolism*; D005971:Glutamates / Q000633:toxicity*; D018698:Glutamic Acid; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
chemical_list: D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D018698:Glutamic Acid; D005947:Glucose