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Focal Cerebral Ischaemia in the Cat: Treatment with the Glutamate Antagonist MK-801 after Induction of Ischaemia

1988; SAGE Publishing; Volume: 8; Issue: 5 Linguagem: Inglês

10.1038/jcbfm.1988.124

1559-7016

C. K. Park, Daniel G. Nehls, David I. Graham, Graham M. Teasdale, James McCulloch,

Neuroscience and Neural Engineering

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 mm 3 of the cerebral hemisphere in vehicle-treated cats to 792 ± 385 mm 3 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.