Dextromethorphan attenuates post-ischemic hypoperfusion following incomplete global ischemia in the anesthetized rat

The effects of dextromethorphan (DM) were tested in an in vivo model of incomplete global cerebral ischemia. Anesthetized rats were divided into 4 groups: Group 1 (saline); Group 2 (DM pre-treatment, 20 mg/kg i.v. bolus followed by 10 mg/kg/h DM infusion); Group 3 (DM post-treatment, 2 mg/kg i.v. bolus followed by 10 mg/kg/h DM infusion at the onset of post-ischemic hypoperfusion); and Group 4 (sham-operated, drug-treated). Groups 1-3 underwent 15 min of 4-vessel occlusion followed by 3 h of reperfusion. Administration of DM in sham-operated animals (Group 4) had no effect on cerebral blood flow or electroencephalographic (EEG) activity. In contrast, when compared to the Group 1 saline controls, significant attenuation of post-ischemic hypoperfusion and EEG dysfunction was demonstrated in ischemic rats treated with DM (both pre- and post-treatment), suggesting an ability of DM to improve cerebral blood flow (CBF) and brain function in cerebral ischemia.