دورية أكاديمية
Seizures triggered by pentylenetetrazol in marmosets made chronically epileptic with pilocarpine show greater refractoriness to treatment
| العنوان: | Seizures triggered by pentylenetetrazol in marmosets made chronically epileptic with pilocarpine show greater refractoriness to treatment |
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| المؤلفون: | Pontes, Josy Carolina Covan UNIFESP, Lima, Thiago Z., Queiroz, Claudio M., Cinini, Simone Maria UNIFESP, Blanco, Miriam Marcela UNIFESP, Mello, Luiz Eugenio Araujo de Moraes UNIFESP |
| بيانات النشر: | Elsevier Science Bv |
| سنة النشر: | 2016 |
| المجموعة: | Universidade Federal de São Paulo (UNIFESP): Repositório Institucional |
| مصطلحات موضوعية: | Epilepsy, Pharmacoresistance, Pentylenetetrazole, Pilocarpine, Anti-epileptic drugs, Animal model |
| جغرافية الموضوع: | Amsterdam |
| الوصف: | The 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. ; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) ; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) ; Univ Fed Sao Paulo, Dept Fisiol, Rua Pedro Toledo ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | 16-25 |
| اللغة: | English |
| تدمد: | 0920-1211 |
| العلاقة: | Epilepsy Research; http://dx.doi.org/10.1016/j.eplepsyres.2016.06.012Test; Epilepsy Research. Amsterdam, v. 126, p. 16-25, 2016.; https://repositorio.unifesp.br/handle/11600/57032Test; WOS:000383825200003 |
| DOI: | 10.1016/j.eplepsyres.2016.06.012 |
| الإتاحة: | https://doi.org/10.1016/j.eplepsyres.2016.06.012Test https://repositorio.unifesp.br/handle/11600/57032Test |
| حقوق: | Acesso restrito |
| رقم الانضمام: | edsbas.9DA4499B |
| قاعدة البيانات: | BASE |
| تدمد: | 09201211 |
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| DOI: | 10.1016/j.eplepsyres.2016.06.012 |