Presented at the American Epilepsy Society annual meeting, San Diego, California, November, 1990 and published in abstract form in Epilepsia 1990;31:635.
Neuroprotective Effect of Ketamine Administered After Status Epilepticus Onset
Article first published online: 3 AUG 2005
Volume 36, Issue 2, pages 186–195, February 1995
How to Cite
Fujikawa, D. G. (1995), Neuroprotective Effect of Ketamine Administered After Status Epilepticus Onset. Epilepsia, 36: 186–195. doi: 10.1111/j.1528-1157.1995.tb00979.x
- Issue published online: 3 AUG 2005
- Article first published online: 3 AUG 2005
- Received August 1993; revision accepted June 1994.
- Status epilepticus;
- Cell death;
Summary We investigated the neuroprotective effect of the noncompetitive N-methyl-d-asparatate (NMDA) antagonist ketamine when administered after onset of lithium-pilocarpine-induced status epilepticus (SE). Seizures were induced in Wistar rats with lithium chloride (3 mEq/kg) and pilocarpine (PC) (30–60 mg/kg intraperitoneally, i.p.). Fifteen minutes after 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. Twentyfour hours later, rats underwent brain perfusion-fixation, with subsequent brain processing for light-microscopic examination. Rats administered saline (n = 5) had neuronal damage in 24 of 25 brain regions examined. Rats administered ketamine (n = 7) had significant neuroprotection in 22 of 24 damaged regions. Ketamine reduced the amplitude of seizure discharges, and in 3 rats EEG seizur activity ceased in 30 min; none of these rats had neuronal damage. In the other 4 rats, EEG seizure discharges persisted >90 min; in these animals, 21 of 24 damaged regions were 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 regions 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.