Introduction and Historical Notes
Excitotoxicity refers to neuronal death caused by activation of excitatory amino acid receptors. Several lines of evidence have linked excitotoxic cell death to the pathogenesis of both acute and chronic neurologic diseases. The initial observation that glutamate was neurotoxic was that of Lucas and Newhouse, who found that administration of glutamate to mice resulted in retinal degeneration (Lucas and Newhouse, 1957). Subsequent studies of Olney and colleagues linked neurotoxicity to the activation of excitatory amino acid receptors, and the term “excitotoxin” was coined (Olney, 1969). Further advances were those of Rothman linking release of excitatory amino acids to anoxic cell death in hippocampal cultures (Rothman, 1984), and of Choi linking calcium influx to delayed cell death caused by excitatory amino acids (Choi, 1987). More work has linked activation of excitatory amino acid receptors to free radical generation and nitric oxide, both of which may lead to oxidative stress (Dawson et al., 1991: Lafon-Cazal et al., 1993).
KeywordsElectron Paramagnetic Resonance Excitatory Amino Acid Kainic Acid Quinolinic Acid Cereb Blood Flow
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