Focal cerebral ischaemia in the cat: treatment with the glutamate antagonist MK-801 after induction of ischaemia

Park, C.K.; Nehls, D.G.; Graham, D.I.; Teasdale, G.M.; McCulloch, J.

Journal of Cerebral Blood Flow and Metabolism Official Journal of the International Society of Cerebral Blood Flow and Metabolism 8(5): 757-762


ISSN/ISBN: 0271-678X
PMID: 2901425
DOI: 10.1038/jcbfm.1988.124
Accession: 071789533

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The effects of the glutamate N-methyl-D-aspartate receptor antagonist MK-801 in reducing ischaemic brain damage have been examined in anaesthetised cats, with drug treatment being initiated 2 h after the induction of cerebral ischaemia. Focal cerebral ischaemia was produced by permanent occlusion of one middle cerebral artery, and the animals were killed 6 h later. The amount of early irreversible ischaemic damage was assessed at 16 predetermined stereotactic planes. Treatment with MK-801 (5 mg/kg, i.v.) 2 h after middle cerebral artery occlusion reduced significantly the volume of ischaemic damage (from 1,625 +/- 384 mm3 of the cerebral hemisphere in vehicle-treated cats to 792 +/- 385 mm3 in MK-801-treated cats). The demonstration of reduced ischaemic brain damage with MK-801, when the agent is administered after the induction of ischaemia, extends the therapeutic potential of such agents in the treatment of focal cerebral ischaemia in humans.