Mild acidosis protects hippocampal neurons from injury induced by oxygen and glucose deprivation.
Hippocampal neurons are extremely sensitive to ischemic injury; two plausible mechanisms have been implicated in mediating such damage. The first involves overexposure of neurons to excitatory N-methyl-D-aspartate (NMDA) receptor agonists, which mobilize damaging concentrations of intracellular calcium; the second involves the generation of damaging tissue acidosis. A recent report shows that exposure to pH 6.6 can block NMDA-induced calcium currents in hippocampal neurons. This suggests that moderate acidity might protect against NMDA-mediated neurotoxicity and ischemic injury in vivo. We have observed such projection in vitro using primary hippocampal cultures. At an extracellular pH of 7.4, 6 h of glucose-free anoxia caused delayed and profound damage to neurons which was partially attenuated by the NMDA receptor antagonist, 2-amino-5-phosphonovaleric acid (APV). Dropping the pH to 6.5 provided virtually complete protection against this insult. Thus, acidosis need not be viewed exclusively as a damaging component of ischemic insults.
Tombaugh
G C
GC
Department of Biological Sciences, Stanford University, CA 94305.
Sapolsky
R M
RM
D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D005947:Glucose