Origins of glutamate release in ischaemia.
Using microdialysis coupled to on-line detection of glutamate, and recording electrical activity and field potential at the same tissue site, We have shown that the increase in extracellular glutamate under global penumbral conditions in minor. However, in the border of the ischaemic core, recurrent spreading depression is presumably associated with transient vesicular release of glutamate (exocytosis). With ischaemic insults severe enough to provoke anoxic depolarization, such as in the ischaemic core, exocytosis only occurred for a few minutes because it requires ATP hydrolysis, and the magnitude of this release was minor in comparison with that of the total glutamate efflux. Subsequent experiments with a selective inhibitor of high-affinity glutamate transporters suggested that reversal of glutamate uptake may not be a major contributor to the sustained release of glutamate in this condition. These results, and other consideration, do not favour the view that presynaptic glutamate release and reversed glutamate uptake are suitable targets for neuroprotection in ischaemia. Acting postsynaptically to inhibit recurrent spreading depression (NMDA-receptor antagonists) or to modulate long-lasting enhancement of synaptic efficiency ('anoxia-induced long-term potentiation' appear to be more rational strategies.
Obrenovitch
T P
TP
Department of Neurology Surgery, Institute of Neurology, London, U.K.
D018528:ATP-Binding Cassette Transporters / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001925:Brain Damage, Chronic / Q000503:physiopathology*; D002545:Brain Ischemia / Q000503:physiopathology*; D013181:Cortical Spreading Depression / Q000502:physiology; D004195:Disease Models, Animal; D005089:Exocytosis / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D017551:Microdialysis; D009410:Nerve Degeneration / Q000502:physiology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D012815:Signal Processing, Computer-Assisted
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D000255:Adenosine Triphosphate