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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on October 30, 2003; DOI: 10.1124/jpet.103.057091

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Received for publication July 18, 2003.
Revised August 22, 2003.
Accepted for publication October 14, 2003.

Neuroprotective effect of topiramate in the lithium- pilocarpine model of epilepsy

Marie-Aude Rigoulot 1, Estelle Koning 1, Arielle Ferrandon 1, Astrid Nehlig 1*

1 INSERM U398

* Address correspondence to: E-mail: nehlig{at}neurochem.u-strasbg.fr

Abstract

Rationale: The lithium-pilocarpine model reproduces the main characteristics of human temporal lobe epilepsy. After status epilepticus (SE), rats exhibit a latent seizure-free phase characterized by development of extensive damage in limbic areas and occurrence of spontaneous recurrent seizures. Neuroprotective and antiepileptogenic effects of topiramate were investigated in this model. Methods: SE was induced in adult male rats by LiCl (3 meq/kg) followed 20 h later by pilocarpine (25 mg/kg). Topiramate (10, 30 or 60 mg/kg) was injected at 1 and 10 h of SE. Injections were repeated twice a day for 6 additional days. Another group received two injections of diazepam on the day of SE and of vehicle for 6 days. Neuronal damage was assessed at 14 days after SE by cell counting on thionin-stained sections. Occurrence of SRS was video recorded for 10 h per day in other groups of rats. Results: In diazepam-treated rats, the number of neurons was dramatically reduced after SE in all subregions of hippocampus and layers II-IV of ventral cortices. At all doses, topiramate induced a 24-30% neuroprotection in layer CA1 of hippocampus (p<0.05). In CA3b, the 30mg/kg dose prevented neuronal death. All rats subjected to SE became epileptic. The latency (14-17 days) to and frequency of SRS were similar in topiramate- and diazepam-treated rats. The high mortality in the 30 mg/kg topiramate group (84%) was possibly the result of interaction between lithium and topiramate. Conclusion: Topiramate displayed neuroprotective properties only in CA1 and CA3 which was not sufficient to prevent epileptogenesis.


Key words: Epileptogenesis, Lithium interaction, Lithium-pilocarpine model, Neuroprotection, Temporal lobe epilepsy, Topiramate


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[Abstract] [Full Text] [PDF]


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