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Amelioration of water maze performance deficits by topiramate applied during pilocarpine-induced status epilepticus is negatively dose-dependent.

Frisch C, Kudin AP, Elger CE, Kunz WS, Helmstaedter C

Department of Epileptology, University of Bonn Medical Center, Sigmund Freud-Straße 25, 53105 Bonn, Germany.

Temporal lobe epilepsy is characterized by a progressive loss of memory capacities, due to sclerosis and functional impairment of mesiotemporal brain areas. We have shown recently that topiramate (TPM) dose-dependently protects hippocampal CA1 and CA3 neurons during initial status epilepticus in the rat pilocarpine model of temporal lobe epilepsy by inhibition of mitochondrial transition pore opening. In the present study, in order to evaluate possible positive effects of the treatment on learning and memory, we investigated water maze performance of rats receiving different dosages of TPM (20 and 100mg/kg) after 40min and 4mg/kg diazepam after 160min of pilocarpine-induced status epilepticus in relation to performance of animals receiving 4mg/kg diazepam after 40min of SE, and to performance of sham-treated control animals. Unexpectedly, 20 but not 100mg/kg TPM significantly extenuated short-term memory deficits. While neuroprotective effects of TPM were observed in hippocampal CA subfields of animals treated with 100mg/kg TPM, cell loss in rats treated with 20mg/kg TPM was indistinguishable from animals receiving diazepam only. The present results indicate a negative dose-dependency of memory-saving effects of TPM applied during status epilepticus apparently dissociated from hippocampal neuroprotection.

Published 19 February 2007 in Epilepsy Res, 73(2): 173-180.
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