Beyond NMDA and AMPA glutamate receptors: emerging mechanisms for ionic imbalance and cell death in stroke

The glutamate receptor was one of the most intensely investigated targets for neuroprotection. However, numerous clinical trials of glutamate receptor antagonists for the treatment of stroke were unsuccessful. These failures have led to pessimism in the field. But recent advances could provide hope...

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Bibliographic Details
Published in:Trends in pharmacological sciences (Regular ed.) 2008-05, Vol.29 (5), p.268-275
Main Authors: Besancon, Elaine, Guo, Shuzhen, Lok, Josephine, Tymianski, Michael, Lo, Eng H
Format: Article
Language:English
Subjects:
Acid-Base Imbalance - metabolism
Acid-Base Imbalance - pathology
Advanced Basic Science
Calcium - physiology
Cell Death
Humans
Ion Channels - physiology
Receptors, AMPA - antagonists & inhibitors
Receptors, AMPA - physiology
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate - physiology
Signal Transduction
Sodium-Calcium Exchanger - physiology
Stroke - metabolism
Stroke - pathology
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Summary:The glutamate receptor was one of the most intensely investigated targets for neuroprotection. However, numerous clinical trials of glutamate receptor antagonists for the treatment of stroke were unsuccessful. These failures have led to pessimism in the field. But recent advances could provide hope for the future. This minireview looks beyond the traditional mechanism of glutamate-receptor-driven excitotoxicity to identify other mechanisms of ionic imbalance. These advances include findings implicating sodium–calcium exchangers, hemichannels, volume-regulated anion channels, acid-sensing channels, transient receptor potential channels, nonselective cation channels and signaling cascades that mediate crosstalk between redundant pathways of cell death. Further in vivo validation of these pathways could ultimately lead us to new therapeutic targets for stroke, trauma and neurodegeneration.
ISSN:0165-6147
1873-3735
DOI:10.1016/j.tips.2008.02.003