Treatment of experimental status epilepticus in immature rats: dissociation between anticonvulsant and antiepileptogenic effects.
We studied the effects of treating status epilepticus (SE) induced by lithium and pilocarpine at postnatal day 15 (P15) or 28 (P28), on the severity of acute SE and of SE-induced epileptogenesis. Rats received topiramate (10 or 50 mg/kg, IP) or diazepam (5 mg/kg, IP) 20, 40 or 70 min after pilocarpine, and three months after SE 24-h video/EEG recordings were obtained for one (P28) or two weeks (P15) continuously. In P15 rats, topiramate did not modify the course of SE, yet treatment at 20 or 40 min completely prevented the development of spontaneous recurrent seizures (SRS) while later treatment (70 min) was partially effective in reducing the severity and frequency of SRS. Diazepam was effective against acute SE at all time points tested. Early (20 min) but not late treatment with diazepam had the effect of reducing the frequency and severity of SRS. In P28 rats, both drugs reduced the cumulative seizure time. Early treatment (20 min) with either drug reduced the incidence of chronic epilepsy. Late treatment (40/70 min) did not alter the incidence of SRS, but decreased their frequency. This study demonstrates that, in the treatment of SE, anticonvulsant and antiepileptogenic effects can be dissociated in a development-specific manner: topiramate was antiepileptogenic without being an effective anticonvulsant in P15 animals at the doses tested. Diazepam, on the other hand, was a better anticonvulsant than an antiepileptogenic agent in the P15 animals at the dose tested. Such effects were not seen in the older animals.
Suchomelova
Lucie
L
Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, 90095, USA. lsuchome@ucla.edu
Baldwin
Roger A
RA
Kubova
Hana
H
Thompson
Kerry W
KW
Sankar
Raman
R
Wasterlain
Claude G
CG
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000627:therapeutic use*; D001285:Atropine / Q000009:adverse effects / Q000627:therapeutic use; D003975:Diazepam / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010862:Pilocarpine / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000188:drug therapy* / Q000503:physiopathology; D000077236:Topiramate
D000927:Anticonvulsants; D010862:Pilocarpine; D000077236:Topiramate; D005632:Fructose; D001285:Atropine; D003975:Diazepam