Status epilepticus induced by pilocarpine and picrotoxin

Status epilepticus induced by pilocarpine and picrotoxin

Autor Hamani, C. Google Scholar
Mello, LEAM Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo Since its original description over 10 years ago, the pilocarpine model of status epilepticus (SE) has gained considerable attention. Much work has been done with the model in order to characterize the involvement of different brain structures in seizure genesis and spread. Electrophysiological studies of temporal lobe epileptic slices of both human and animal models, have failed to reveal hyperexcitability, unless blockade of GABAergic inhibition is performed. Thus, we have decided to evaluate potential contributions of picrotoxin, a GABA, channel blocker, on pilocarpine-induced SE. Animals injected with three specific dose combinations (pilocarpine dose/picrotoxin dose), 150/0.5, 75/1.5 and 50/2.0 mg/kg, evoked status epilepticus (SE) within 23, 31 and 27 min, respectively. Ictal events and EEG spikes were initially observed either in the amygdala or in the hippocampus, with a later spread to cerebral cortex. Neuropathological analysis, performed 5-7 days after SE, has shown a high degree of cell loss predominantly in the piriform cortex, amygdala, hippocampus, thalamus and substantia nigra. Mortality rates for 150/0.5, 75/1.5 and 50/2.0 mg/kg (pilocarpine dose/picrotoxin dose) were 53, 42 and 51%, respectively. Single injections of 150 mg/kg of pilocarpine or 3 mg/kg of picrotoxin did not evoke any form of sustained epileptic activity. Previous studies in which simultaneous injections of other GABA(A) antagonists (i.e. bicuculline) and pirocarpine were performed, did not show clear evidences of a synergistic action between these two systems. the present study reveals a proconvulsant role for picrotoxin when co-administered with subconvulsant doses of pilocarpine. Possible mechanisms that might account for the interactions between the cholinergic and GABAergic systems in regard to epileptogenesis are discussed. (C) 1997 Elsevier Science B.V.
Palavra-chave acetylcholine
models of epilepsy
Idioma Inglês
Data de publicação 1997-07-01
Publicado em Epilepsy Research. Amsterdam: Elsevier B.V., v. 28, n. 1, p. 73-82, 1997.
ISSN 0920-1211 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 73-82
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:A1997XL61200008
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