Dextromethorphan protects against cerebral injury following transient focal ischemia in rabbits.

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Abstract
We investigated dextromethrophan, both a dextrorotatory opioid dervative and a clinically tested N-methyl-D-aspartate (NMDA) receptor antagonist, in a rabbit model of transient focal cerebral ischemia. Fourteen rabbits were randomly assigned to treat ment with a 20 mg/kg i.v. loading dose followed by a 10 mg/kg/hr infusion of 0.4% dextromethorphan in normal saline or with an equivalent volume of normal saline alone. One hour after treatment, the rabbits underwent a 1-hour occlusion of the left internal carotid and anterior cerebral arteries followed by 4 hours of reperfusion. The seven dextromethrophan-treated rabbits showed a significant decrease in the area of neocortical severe ischemic neuronal damage (10.5%) compared with the seven normal saline-treated contorls (49.6%, p < 0.001). The dextromethrophan-treated rabbits also demonstrated significantly smaller areas of cortical edema (10.2%) on magnetic resonance imaging than the controls (38.6%, p < 0.01). Analysis of soma tosensory evoked potentials revealed recovery of controls (38.65, p < 0.01). Analysis of somatosensory evoked potentials reperfusoin in the dextromethrophan-treated rabbits but not in the contorls (p < 0.01). In our rabbit model of transient focal cerebral ischemia, dextromethrophan appears to protect the brain against ischemic neuronal damage and edema, as well as to promote neurophysiologic recovery. THis clinically available drug should be further investigated as having potential therapeutic value in the treatment of stroke.