Ischemic neuronal damage after acute subdural hematoma in the rat: effects of pretreatment with a glutamate antagonist.
The ability of a competitive N-methyl-D-aspartate (NMDA) receptor antagonist (D-CPP-ene) to reduce irreversible brain damage has been examined in a rodent model of acute subdural hematoma. Acute subdural hematoma was produced by the slow injection of 400 microliters homologous blood into the subdural space overlying the parietal cortex in halothane-anesthetized rats. Brain damage was assessed histologically in sections at multiple coronal planes in animals sacrificed 4 hours after induction of the subdural hematoma. Pretreatment with D-CPP-ene (15 mg/kg) significantly reduced the volume of ischemic brain damage produced by the subdural hematoma from 62 +/- 8 cu mm (mean +/- standard error of the mean) in vehicle-treated control rats to 29 +/- 7 cu mm in drug-treated animals. These data demonstrate the anti-ischemic efficacy of NMDA antagonists in an animal model of intracranial hemorrhage in which intracranial pressure is elevated, and suggest that excitotoxic mechanisms (which are susceptible to antagonism by D-CPP-ene) may play a role in the ischemic brain damage which is observed in patients who die after acute subdural hematoma.
Chen
M H
MH
Institute of Neurological Sciences, University of Glasgow, Scotland.
Bullock
R
R
Graham
D I
DI
Miller
J D
JD
McCulloch
J
J
D000818:Animals; D002545:Brain Ischemia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006408:Hematoma, Subdural / Q000150:complications* / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009943:Organophosphorus Compounds / Q000097:blood / Q000494:pharmacology*; D010879:Piperazines / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009943:Organophosphorus Compounds; D010879:Piperazines; C065286:SDZ EAA 494