Amelioration of water maze performance deficits by topiramate applied during pilocarpine-induced status epilepticus is negatively dose-dependent.
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 100 mg/kg) after 40 min and 4 mg/kg diazepam after 160 min of pilocarpine-induced status epilepticus in relation to performance of animals receiving 4 mg/kg diazepam after 40 min of SE, and to performance of sham-treated control animals. Unexpectedly, 20 but not 100 mg/kg TPM significantly extenuated short-term memory deficits. While neuroprotective effects of TPM were observed in hippocampal CA subfields of animals treated with 100 mg/kg TPM, cell loss in rats treated with 20 mg/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.
Frisch
Christian
C
Department of Epileptology, University of Bonn Medical Center, Sigmund Freud-Strasse 25, 53105 Bonn, Germany. Christian.Frisch@ukb.uni-bonn.de
Kudin
Alexei P
AP
Elger
Christian E
CE
Kunz
Wolfram S
WS
Helmstaedter
Christoph
C
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*; D013550:Swimming; D000077236:Topiramate; D014741:Video Recording; D014867:Water
D000927:Anticonvulsants; D018696:Neuroprotective Agents; D010862:Pilocarpine; D014867:Water; D000077236:Topiramate; D005632:Fructose; D003975:Diazepam