[Influence of excitatory amino acids on the outcome of cerebral ischemia].
It would appear from an analysis of the molecular mechanisms which determine the post-ischaemic destruction of brain tissue that they primarily involve the action of excitatory aminoacids, together with the inhibition of protein synthesis and the disorderly production of free radicals. The activities of endogenous excitatory aminoacids (glutamate, aspartate) immediately after ischaemia are similar to those of exogenous excitotoxins (kainic acid, N-methyl-D-aspartate). Brain tissue destruction consecutive to ischaemia or hypoglycaemia is mainly found in cerebral structures which contain a large number of glutamate receptors (hippocampus, locus coeruleus, corpus striatum). These lesions are associated with a significant increase in extracellular concentrations of excitatory aminoacids which are responsible for the massive penetration and accumulation of calcium in the cells (nucleus, Golgi complex, mitochondria), and this encourages the synthesis of non-functional proteins and/or proteolysis (direct cytotoxic action). In animals, these post-ischaemic necrotic lesions are prevented by administration of pharmacological antagonists of these neuromediators at receptor level (e.g. 2-amino-7-phosphonoheptanoic acid). These experimental results suggest that excitatory aminoacids play a determinant role in the genesis of post-ischaemic cell death and that the glutamatergic antagonists currently under development may have a therapeutic activity.
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival; D002712:Chlorides / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017459:Receptors, Amino Acid; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D005971:Glutamates; D017459:Receptors, Amino Acid; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; C031959:aspartic acid receptor; D001224:Aspartic Acid; D012964:Sodium; D002118:Calcium
Influence des amino-acides excitateurs sur le devenir de l'ischémie cérébrale.