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Journal of Neuroscience, Vol 4, 1884-1891, Copyright © 1984 by Society for Neuroscience
Synaptic release of excitatory amino acid neurotransmitter mediates anoxic neuronal death
S Rothman
The pathophysiology of hypoxic neuronal death, which is difficult to study
in vivo, was further defined in vitro by placing dispersed cultures of rat
hippocampal neurons into an anoxic atmosphere. Previous experiments had
demonstrated that the addition of high concentrations of magnesium, which
blocks transmitter release, protected anoxic neurons. These more recent
experiments have shown that gamma-D- glutamylglycine (DGG), a postsynaptic
blocker of excitatory amino acids, was highly effective in preventing
anoxic neuronal death. DGG also completely protected the cultured neurons
from the toxicity of exogenous glutamate (GLU) and aspartate (ASP). In
parallel physiology experiments, DGG blocked the depolarization produced by
GLU and ASP, and dramatically reduced EPSPs in synaptically coupled pairs
of neurons. These results provide convincing evidence that the synaptic
release of excitatory transmitter, most likely GLU or ASP, mediates the
death of anoxic neurons. This result has far-reaching implications
regarding the interpretation of the existing literature on cerebral
hypoxia. Furthermore, it suggests new strategies that may be effective in
preventing the devastating insults produced by cerebral hypoxia and
ischemia in man.
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