NEUROPROTECTIVE EFFECT OF KETAMINE ADMINISTERED AFTER STATUS EPILEPTICUS ONSET

We investigated the neuroprotective effect of the noncompetitive N-met hyl-D-asparatate (NMDA) antagonist ketamine when administered after on set of lithium-pilocarpine-induced status epilepticus (SE). Seizures w ere induced in Wistar rats with lithium chloride (3 mEq/kg) and piloca rpine (PC) (30-60 mg/kg intraperitoneally, i.p.). Fifteen minutes afte r SE onset, either ketamine 100 mg/kg or normal saline was injected i. p., and 3 h after SE onset atropine, diazepam (DZP), and phenobarbital (PB) were administered i.p. to terminate the seizures. Twenty-four ho urs later, rats underwent brain perfusion-fixation, with subsequent br ain processing for light-microscopic examination. Rats administered sa line (n = 5) had neuronal damage in 24 of 25 brain regions examined. R ats administered ketamine (n = 7) had significant neuroprotection in 2 2 of 24 damaged regions. Ketamine reduced the amplitude of seizure dis charges, and in 3 rats EEG seizure activity ceased in 30 min; none of these rats had neuronal damage. In the other 4 rats, EEG seizure disch arges persisted >90 min; in these animals, 21 of 24 damaged regions we re protected. In contrast, rats with 1-h high-dose PC-induced SE (400 mg/kg i.p. without lithium chloride preadministration) had 14 damaged regions, of which 7 were significantly different from the undamaged re gions of the ketamine subgroup with persistent electrographic seizures . Thus, ketamine is remarkably neuroprotective when administered after onset of SE, whether or not seizure discharges are eliminated.