Glutamate and the pathophysiology of hypoxic--ischemic brain damage.
Information obtained over the past 25 years indicates that the amino acid glutamate functions as a fast excitatory transmitter in the mammalian brain. Studies completed during the last 15 years have also demonstrated that glutamate is a powerful neurotoxin, capable of killing neurons in the central nervous system when its extracellular concentration is sufficiently high. Recent experiments in a variety of preparations have shown that either blockade of synaptic transmission or the specific antagonism of postsynaptic glutamate receptors greatly diminishes the sensitivity of central neurons to hypoxia and ischemia. These experiments suggest that glutamate plays a key role in ischemic brain damage, and that drugs which decrease the accumulation of glutamate or block its postsynaptic effects may be a rational therapy for stroke.
S M
SM
Rothman
J W
JW
Olney
D000818:Animals; D001418:Baclofen / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002415:Cats; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects; D013181:Cortical Spreading Depression; D004151:Dipeptides; D005971:Glutamates / Q000378:metabolism* / Q000633:toxicity; D018698:Glutamic Acid; D006624:Hippocampus / Q000503:physiopathology; D007027:Hypothalamic Diseases / Q000139:chemically induced; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D007473:Ion Channels / Q000502:physiology; D051379:Mice; D011817:Rabbits; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000032:analysis; D012162:Retinal Degeneration / Q000139:chemically induced; D009435:Synaptic Transmission
D002121:Calcium Channel Blockers; D004151:Dipeptides; D005971:Glutamates; D007473:Ion Channels; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; C028929:gamma-glutamylglycine; D018698:Glutamic Acid; D001418:Baclofen