Tóm tắt

In the Introduction to the first edition of this book, the history behind the concept of excitotoxicity was described, from John Olney’s initial descriptions of the phenomenon (Olney 1969, 1971; Olney et al. 1974) through subsequent studies identifying the mechanisms by which excessive glutamate release presynaptically and by reversal of astrocytic glutamate uptake results in postsynaptic neuronal death. A synaptic mechanism was identified in 1983 (Rothman 1983), followed by identification of calcium entry via the n -methyl-d-aspartate (NMDA) subtype of glutamate receptor (MacDermott et al. 1986) and excessive calcium entry through the NMDA receptoroperated cation channel as the mechanism by which neurons died (Choi 1987; Choi et al. 1987). Early electron-microscopic studies of neuronal death from experimental cerebral ischemia (McGee-Russell et al. 1970), hypoglycemia (Auer et al. 1985a, b; Kalimo et al. 1985) and status epilepticus (Griffiths et al. 1983; Ingvar et al. 1988) showed electron-dense, shrunken neurons with pyknotic nuclei containing irregular chromatin clumps and dilated mitochondria, which the authors called “dark-cell degeneration.” These were morphologically identical to the neurons that Olney found following exposure to glutamate or its analogues. We now call these neurons “necrotic,” to differentiate them from “apoptotic” neurons (Fujikawa 2000, 2002), both of which die from different programmed mechanisms