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dc.contributor.authorPontes, Josy Carolina Covan [UNIFESP]
dc.contributor.authorLima, Thiago Z.
dc.contributor.authorQueiroz, Claudio M.
dc.contributor.authorCinini, Simone Maria [UNIFESP]
dc.contributor.authorBlanco, Miriam Marcela [UNIFESP]
dc.contributor.authorMello, Luiz Eugenio Araujo de Moraes [UNIFESP]
dc.identifier.citationEpilepsy Research. Amsterdam, v. 126, p. 16-25, 2016.
dc.description.abstractThe efficiency of most of the new antiepileptic drugs (AEDs) on clinical trials still falls short the success reported in pre-clinical studies, possibly because the validity of the animal models is insufficient to fully represent the human pathology. To improve the translational value for testing AEDs, we propose the use of non-human primates. Here, we suggest that triggering limbic seizures with low doses of PTZ in pilocarpine-treated marmosets might provide a more effective basis for the development of AED. Marmosets with epileptic background were more susceptible to seizures induced by PTZ, which were at least 3 times longer and more severe (about 6 times greater frequency of generalized seizures) in comparison to naive peers. Accordingly, PTZ-induced seizures were remarkably less attenuated by AEDs in epileptic than naive marmosets. While phenobarbital (40 mg/kg) virtually abolished seizures regardless of the animal's background, carbamazepine (120 mg/kg) and valproic acid (400 mg/kg) could not prevent PTZ-induced seizures in epileptic animals with the same efficiency as observed in naive peers. VPA was less effective regarding the duration of individual seizures in epileptic animals, as assessed in ECoG (p = 0.05). Similarly following CBZ treatment, the behavioral manifestation of generalized seizures lasted longer in epileptic (p < 0.05), which were also more frequent than in the naive group (p < 0.05). As expected, epileptic marmosets experiencing stronger seizures showed more NPY- and Delta FosB-immunostained neurons in a number of brain areas associated with the generation and spread of limbic seizures. Our results suggest that PTZ induced seizures over an already existing epileptic background constitutes a reliable and controllable mean for the screening of new AEDs. (C) 2016 Elsevier B.V. All rights reserved.en
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.publisherElsevier Science Bv
dc.relation.ispartofEpilepsy Research
dc.rightsAcesso restrito
dc.subjectAnti-epileptic drugsen
dc.subjectAnimal modelen
dc.titleSeizures triggered by pentylenetetrazol in marmosets made chronically epileptic with pilocarpine show greater refractoriness to treatmenten
dc.description.affiliationUniv Fed Sao Paulo, Dept Fisiol, Rua Pedro Toledo 669,3 Andar, BR-04039032 Sao Paulo, SP, Brazil
dc.description.affiliationHosp Israelita Albert Einstein, Ave Albert Einstein 627, BR-05652000 Sao Paulo, SP, Brazil
dc.description.affiliationUniv Fed Rio Grande do Norte, Inst Brain, Ave Nascimento de Castro 2155, BR-59056450 Natal, RN, Brazil
dc.description.affiliationUnifespDepartamento de Fisiologia, Universidade Federal de São Paulo, Rua Pedro de Toledo 669, 3 andar, São Paulo, SP 04039-032, Brazil
dc.description.sourceWeb of Science

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