Avaliação eletrofisiológica in vitro de drogas antiepilépticas em fatias hipocampais humanas provenientes de pacientes portadores de epilepsia do lobo temporal refratária ao tratamento medicamentoso

• Autor(a) principal: Silva,André César da
• Data de Publicação: 2006
• Outros Autores: Yacubian,Elza Márcia Targas, Sakamoto,Américo Ceiki, Centeno,Ricardo da Silva, Ueda,Érika Sayuri, Antônio,Leandro Leite, Faria,Leonardo Coutinho, Priel,Margareth Rose, Cavalheiro,Esper Abrão
• Tipo de documento: Artigo
• Idioma: por
• Título da fonte: Journal of epilepsy and clinical neurophysiology (Online)
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1676-26492006000300005
• topic: drogas antiepilépticas; electrofisiologia in vitro; drogas resistentes

The absence of a satisfactory response to antiepileptic drug (AED) therapy, is an unresolved problem in a significant number of epileptic patients. Mechanisms of intractability are not well understood but may include a combination of poor penetration of AED across a functionally altered blood-brain barrier owing to increased expression of multiple drug resistance transporters. Therefore, the aim of this work was to assess the in vitro efficacy of antiepileptic drugs through human hippocampal slices originating from patients with refractory temporal lobe epilepsy submitted to corticoamygdalohippocampectomy. Slices was prepared from a 1 cm³ block of the hippocampus body 30 min after resection. Briefly, hippocampal slices of 400 µM thickness was cut coronally. Extracellular field potentials was recorded from the st. Granulosum of the dentate gyrus. The antiepileptic drugs added in the bath were Carbamazepine, Topiramate and Phenytoin. The phenytoin was effective reducing the hyperexcitability (polispikes) in 60% of the experiments (n = 5). On the other hand, the carbamazepine promoted a decrease in evoked epileptiform activity in 37,5% of the cases (n = 8). The application of topiramate in the bath reduced in 30% the number of polispikes (n = 10). Our results showed that the phenytoin application resulted in a significant reduction in neuronal excitability, however, the carbamazepine and topiramate were not able to control of the hiperexcitability, suggesting that local neuronal alterations, as well changes in blood brain barrier, could be responsible for such behaviors.