Protection against ischaemic neuronal damage by drugs acting on excitatory neurotransmission
Meldrum, B.
Cerebrovascular and Brain Metabolism Reviews 2(1): 27-57
1990
ISSN/ISBN: 1040-8827 PMID: 2169834 Document Number: 364895
An excitotoxic action of glutamate and aspartate contributes to the pathological outcome after transient global cerebral ischaemia, focal ischaemia, neonatal hypoxia/ischaemia, and secondary ischaemia following brain trauma. This provides a therapeutic approach utilising drugs acting on (i) glutamate release, (ii) postsynaptic glutamate receptors, and (iii) the secondary events following receptor activation (including the arachidonic acid cascade). Both NMDA and non-NMDA receptors are involved in the excitotoxic effects of glutamate and aspartate. The availability of competitive and noncompetitive antagonists acting at the NMDA receptor has permitted the demonstration of cerebroprotective effects of these compounds in animal models of global, focal, neonatal, and secondary cerebral ischaemia. Protection is seen with antagonist administration prior to and after the onset of ischaemia. The postischaemic therapeutic time window is not fully defined for the different models but is in the range of 0-20 min for incomplete global ischaemia and 1-3 h for focal ischaemia. The clinical usefulness of this approach remains to be established.