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, on 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 all animals were characterized by well-circumscribed infarctions underlying the subdural hematoma. Lesion volume in control animals was 88.3 +/- 9.3 mm3 (mean +/- standard error of the mean), while animals receiving dextromethorphan had significantly smaller lesions, which was independent of dosing schedule (59.9 +/- 9.2 mm3)(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.
Duhaime
A C
AC
Division of Neurosurgery, Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine 19104, USA.
Gennarelli
L M
LM
Boardman
C
C
D000818:Animals; D003915:Dextromethorphan / Q000494:pharmacology*; D004195:Disease Models, Animal; D006406:Hematoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051381:Rats; D013355:Subdural Space / Q000187:drug effects*; D013997:Time Factors
D003915:Dextromethorphan