Excitotoxicity, Cerebral Ischemia, and Neuroprotection by Competitive NMDA Receptor Antagonists
The concept of excitotoxicity, meaning the damage or death of neurons resulting from hyperactivation of excitatory cellular mechanisms, arose from the extensive histologic studies of Olney and his colleagues during the early 1970s. These investigators found that excitatory amino acids such as glutamate, when administered to immature rodents, induced degenerative changes in neurons in the retina and in the hypothalamus (Olney, 1971; Olney et al., 1971). Subsequent studies showed that there was a good correlation between the neurotoxic and neuroexcitatory potencies of a range of related amino acids, suggesting that there was a direct causal relationship between cellular activation and cell death (see Rothman and Olney, 1987).
KeywordsNMDA Receptor Cerebral Ischemia Middle Cerebral Artery Occlusion Excitatory Amino Acid NMDA Receptor Antagonist
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