Neuroprotection by dextromethorphan in acute experimental subdural hematoma in the rat

Experimental acute subdural hematoma in the rat has been shown to produce a zone of apparent infarction under the clot, and excitatory amino acid toxicity appears to play a role in the damage observed, We report the effect of dextromethorphan, a commonly used antitussive and a noncompetitive NMDA-type glutamate receptor antagonist, an the volume of histologic damage seen at 72 h after acute subdural hematoma in the rat, Sixty-five Long-Evans rats underwent placement of acute subdural hematoma using the ''cranial window'' model, Fourteen animals received oral dextromethorphan, 10 mg/kg/dose, twice daily for 3 days, and an additional 20 animals also received a single 20 mg/kg intraperitoneal dose 15 min after clot placement in addition to the oral regimen, Control animals received equal volumes of sterile water. Brain lesions in ail animals were characterized by well-circumscribed infarctions underlying the subdural hematoma, Lesion volume in control animals was 88.3 +/- 9.3 mm(3) (mean +/- standard error of the mean), while animals receiving dextromethorphan had significantly smaller lesions, which was independent of dosing schedule (59.9 +/- 9.2 mm(3))(p = 0.0403), Animal weight was also found to be a significant covariate (p = 0.038), Because of its safety in humans and efficacy as a neuroprotectant in a variety of models, dextromethorphan may be a promising agent for clinical use, particularly in children.