[Glutamate neurotransmission and calcium metabolism in cerebral ischaemia and under normal conditions].
This article is dedicated to the mechanisms of ischaemic brain damage. The processes of glutamate-calcium cascade connected with formation of focal brain necrosis within the period of therapeutic window (the first 3-6 h after the induction of cerebral ischaemia) are discussed. The basis mechanisms of energy-dependent ionic pumps failure, development of glutamate excitotoxicity, disorders of calcium metabolism are analyzed. The results of own investigations are presented. The significant increases in the concentrations of excitatory aminoacidergic neurotransmitters (glutamate and aspartate) in the cerebrospinal fluid were demonstrated in patients with acute ischaemic strokes from the first hours of illness with no dependency on vascular origin of strokes. The extent and duration of these increases were of prognostic value for determining the severity and outcome of the stroke. It was showed that along with "excitotoxicity", the pathogenesis of ischaemic stroke also involves a deficiency of protective inhibitory GABAergic mechanisms and developing imbalance between the excitatory and inhibitory neurotransmitters systems. The significant increase of the level of the specific autoantibodies to phencyclidine-binding protein of glutamate NMDA-receptors was found out in blood serum of patients beginning from the first 3 h after stroke onset and it directly correlated with the severity of ischaemic stroke. The great attention is paid to the role of astroglia in energy metabolism and glutamate neurotransmission, to the mechanisms of regulation of concentrations of neurotransmitter amino acids in the synaptic cleft, as well as to the mechanisms of spreading depression waves and zinc neurotoxicity.
Gusev
E I
EI
Russian State Medical University, Moscow.
Skvortsova
V I
VI
D001224:Aspartic Acid / Q000134:cerebrospinal fluid / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D002545:Brain Ischemia / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D018698:Glutamic Acid / Q000134:cerebrospinal fluid* / Q000502:physiology; D006801:Humans; D017136:Ion Transport; D009474:Neurons / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology; D020521:Stroke / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology; D009435:Synaptic Transmission
D016194:Receptors, N-Methyl-D-Aspartate; D001224:Aspartic Acid; D018698:Glutamic Acid; D002118:Calcium