EFFECT OF ANESTHETICS ON NEUROPATHOLOGIC SEQUELAE OF STATUS EPILEPTICUS IN RATS

We compared the efficacy of four different classes of anesthetics to a rrest the progression of brain damage after chemoconvulsant-induced se izures in rats. In two series of experiments, ventilated, paralyzed Lo ng-Evans rats were subjected to 30 or 45 min of continuous seizures in duced by intravenous (IV) mercaptopropionic acid (MPA) or inhaled flur othyl, respectively. In the first series, seizures produced with MPA w ere treated with: 1) thiopental, 15 mg/kg IV bolus (controls); 2) thio pental, 27 mg/kg IV followed by 20.9 mg.kg-1.h-1 for 2 h; 3) isofluran e 4% inhaled concentration for 1 min followed by 1%-2% for 2 h; 4) ket amine 30 mg/kg IV followed by 9.12 mg.kg-1.h-1 for 2 h; 5) midazolam 2 5 mg/kg IV followed by 9.7 mg.kg-1.h-1 for 2 h. In a second series, se izures were produced by flurothyl and, based on suggestive results in the MPA series, control rats were compared with rats receiving midazol am 25 mg/kg IV followed by 9.7 mg.kg-1.h-1. In all instances, seizure activity, recorded by electroencephalograph, stopped with anesthetic t reatment. In MPA-treated rats extranigral damage was mild, with no dif ferences apparent between anesthetics. Control animals sustained sever e lesions in the substantia nigra pars reticulata (SNPR). No statistic ally significant differences between anesthetic groups were present, a lthough an effect was suggested for midazolam to decrease SNPR lesiona l area (P = 0.06). In flurothyl-treated rats, there were significant r eductions in SNPR neuropathologic grade (P = 0.025) and lesional area (P = 0.025) with midazolam. We conclude that midazolam attenuates post seizure SNPR damage in rats.