title: Phenytoin protects against ischemia-produced neuronal cell death.
abstract: Brief bilateral carotid occlusion in the gerbil produces forebrain ischemia that results in almost complete neuronal destruction in the CA1 sector of the hippocampus. Treatment with phenytoin (200 mg/kg) blocked the ischemia-induced neuronal death. The average density of CA1 pyramidal neurons (cells/mm CA1) was 253.6 +/- 4.4 in the sham surgery group, 12.3 +/- 3.4 in the ischemia group, and 119.5 +/- 16.6 in the group treated with phenytoin before ischemia. Thus, phenytoin reduced ischemia-produced neuronal loss in hippocampal CA1 by 44.4% (P less than 0.001). The plasma levels of phenytoin that produced this effect ranged from 28.1 to 45.0 mg per liter, with a mean phenytoin level of 34.7 +/- 1.7 mg/l (n = 10). The results suggest that phenytoin may be a clinically useful cerebroprotective agent.
authors.affiliation: Department of Neurology, Medical College of Virginia, Richmond 23298.
authors.forename: W C
authors.initials: WC
authors.lastname: Taft
authors.forename: G L
authors.initials: GL
authors.lastname: Clifton
authors.forename: R E
authors.initials: RE
authors.lastname: Blair
authors.forename: R J
authors.initials: RJ
authors.lastname: DeLorenzo
mesh_terms: D000818:Animals; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010672:Phenytoin / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D010672:Phenytoin