Summary
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 is 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 considerations, do not favour the view that presynaptic glutamate release and reversed glutamate uptake are suitable targets for neuroprotection in ischaemia. Acting post-synaptically 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.
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© 1996 Springer-Verlag
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Obrenovitch, T.P. (1996). Origins of Glutamate Release in Ischaemia. In: Baethmann, A., Kempski, O.S., Plesnila, N., Staub, F. (eds) Mechanisms of Secondary Brain Damage in Cerebral Ischemia and Trauma. Acta Neurochirurgica, vol 66. Springer, Vienna. https://doi.org/10.1007/978-3-7091-9465-2_9
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