Dextromethorphan protects against cerebral infarction in a rat model of hypoxia-ischemia

We assessed the cerebral protective effects of the noncompetitive N-methyl-D-aspartate antagonist dextromethorphan (DM; 10-35 mg/kg i.p.) in 8-day-old rats that were subjected to brain hypoxia-ischemia by tying one carotid artery and placing them in 8% O2-92% N2 for 2 h. Light microscopic examination of brains perfused one week after the insult revealed that all control animals developed a frank infarction with cavitation and brain shrinkage in the middle cerebral artery territory. There was a highly significant decrease in the incidence of frank infarction in DM-pre-treated pups vs saline-treated littermates, although there was no clear relationship between drug dose and the degree of brain protection. DM and its active metabolite dextrorphan may prove to be clinically useful in protecting against hypoxia-ischemia.