Role of excitotoxins in developmental neuropathology.
Many years ago, it was found that glutamate has both neuroexcitatory and neurotoxic (excitotoxic) properties and that the central nervous system is more sensitive to glutamate excitotoxicity during development than in adulthood. In recent years accumulating evidence has implicated glutamate in the pathophysiology of several neurodegenerative disorders. Although the primary emphasis of this research has been on adult-onset neurological disorders, studies focusing on the developing CNS have corroborated the extreme sensitivity of the immature CNS to the excitotoxic actions of glutamate and related excitotoxins, especially those that interact selectively with the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Recent findings pertaining to the potential role of excitotoxic mechanisms in developmental neuropathology will be reviewed with special emphasis on hypoxic-ischemic and related forms of neuropathology which appear to be mediated through NMDA receptors.
Olney
J W
JW
Department of Psychiatry and Pathology, Washington University Medical School, St. Louis, Missouri 63110.
D000592:Amino Acid Metabolism, Inborn Errors / Q000378:metabolism; D001224:Aspartic Acid / Q000502:physiology*; D001927:Brain Diseases / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology*; D003001:Cloning, Molecular; D003545:Cysteine / Q000633:toxicity; D005971:Glutamates / Q000502:physiology*; D005998:Glycine / Q000378:metabolism; D006801:Humans; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000172:deficiency; D017470:Receptors, Glutamate / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D005971:Glutamates; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D050862:Oxidoreductases Acting on Sulfur Group Donors; D003545:Cysteine; D005998:Glycine