Avaliação eletrofisiológica in vitro de drogas antiepilépticas em fatias hipocampais humanas provenientes de pacientes portadores de epilepsia do lobo temporal refratária ao tratamento medicamentoso / In vitro electrophysiological assessment of antiepileptic drugs in human hippocampal slices originating from patients with refractory temporal lobe epilepsy

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.

Gap junctions in human hippocampal sclerosis

Um grande número de portadores de epilepsia do lobo temporal não obtém controle de suas crises com os medicamentos antiepilépticos atualmente disponíveis. Nesses casos de epilepsia fármaco-resistente uma possibilidade terapêutica é a ressecção cirúrgica do foco epiléptico. Estudos em preparações de fatias hipocampais de tecido epileptogênico proveniente da cirurgia de epilepsia tem mostrado a ocorrência de junções comunicantes (gap junctions) o que poderia estar relacionada com o hipersincronismo observado no foco epiléptico. Neste trabalho, nós mostramos estudos eletrofisiológicos in vitro feitos na formação hipocampal obtida de um paciente após uma cirurgia de epilepsia. População de espículas (Population spikes) de pequena amplitude foram registradas sugerindo uma lesão neuronal significante. As propriedades intrínsicas de membranas obtidas desses neurônios mostraram-se normais. A presença das junções comunicantes nas células granulares do giro dentado também foram observadas. Nossos achados sugerem que a presença de junções comunicantes no tecido epiléptico pode ter um papel importante na geração de descargas epileptiformes