Glutamate-Mediated Excitotoxicity

  • G. A. Kerchner
  • A. H. Kim
  • D. W. Choi
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 141)

Abstract

Excitotoxicity — the ability of glutamate receptor activation to trigger neuronal cell death — has been recognized for more than four decades (Lucas and New-house 1957; Olney 1969; Choi 1988b). Over the last 10–15 years, there has been an accumulation of evidence that suggests that glutamate toxicity contributes to brain or spinal cord tissue damage in a variety of disease settings, such as brain ischemia, seizures, traumatic brain injury, and hypoglycemia. The concept of excitotoxicity has undergone substantial evolution. The earlier notion that glutamate receptors must be overactivated to induce cell death has yielded to a newer view that physiological levels of activation may be lethal to neurons rendered vulnerable by energy depletion or other derangements. Recent evidence suggesting that oligodendrocytes may be as susceptible to excitotoxicity as many neurons has further broadened the original definition of this process. In addition, as distinctions between necrosis and programmed cell death have become better defined, increased scrutiny has been accorded to the modes of cell death induced by glutamate-receptor activation. Furthermore, with an explosion of new knowledge regarding the molecular composition and modulation of ionotropic glutamate receptors, an increased appreciation of how these factors may affect excitotoxicity is developing. Finally, the late downstream effectors of excitotoxic cell death are beginning to be recognized.

Keywords

Zinc Permeability Toxicity Retina Triphosphate 

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© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • G. A. Kerchner
  • A. H. Kim
  • D. W. Choi

There are no affiliations available

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