Carbamazepine-resistance in the epileptic dentate gyrus of human hippocampal slices

Show simple item record Jandova, Katerina Paesler, Dennis Antônio, Leandro Leite [UNIFESP] Raue, Claudia Ji, Shengbo Njunting, Marleisje Kann, Oliver Kovacs, Richard Meencke, Heinz-Joachim Cavalheiro, Esper Abrão [UNIFESP] Heinemann, Uwe Gabriel, Siegrun Lehmann, Thomas-Nicolas 2016-01-24T12:41:35Z 2016-01-24T12:41:35Z 2006-12-01
dc.identifier.citation Brain. Oxford: Oxford Univ Press, v. 129, p. 3290-3306, 2006.
dc.identifier.issn 0006-8950
dc.description.abstract Overexpression of drug efflux pumps at the blood brain barrier (BBB) has been suggested to be one important factor contributing to drug resistance in epilepsy. This would imply that resected brain tissue of drug-resistant patients is drug-sensitive in absence of the BBB. Here we studied the effects of carbamazepine (CBZ) at therapeutically relevant concentration on epileptiform activity electrophysiologically recorded in acute hippocampal slices of patients with mesial temporal lobe epilepsy (MTLE; 28 patients, 49 slices) or extra-hippocampal tumours (tumour; 6 patients, 11 slices). Epileptiform activity was induced by hilar stimulation (0.067 Hz) during elevation of extracellular potassium concentration ([K+](o)) and remained self-sustained in presence of 10-12 mM [K+](o). Quantitative analysis of data revealed that epileptiform activity in tissue of tumour-patients was predominantly suppressed by CBZ, indicating that the 'epilepsy model' used is CBZ-sensitive. in contrast, epileptiform activity in tissue of drug-resistant MTLE patients was resistant to CBZ in 82% of patients, partially suppressed in 11% and completely suppressed in 7%. the effects of CBZ in tissue of MTLE patients did not depend on the type of activity, hippocampal pathology, excitability of the tissue, or equilibration time of the drug. Considering that CBZ has direct access to all compartments of the slice, our results suggest that CBZ-resistance mechanisms are located within the parenchyma of the dentate gyrus and contribute to drug resistance in the majority of MTLE patients. BBB-located drug-resistance mechanisms per se may play a minor role in this region, because CBZ-sensitivity was only observed in 7% of CBZ-resistant patients. en
dc.format.extent 3290-3306
dc.language.iso eng
dc.publisher Oxford Univ Press
dc.relation.ispartof Brain
dc.rights Acesso aberto
dc.subject drug resistance en
dc.subject electrophysiology en
dc.subject epilepsy en
dc.subject hippocampus en
dc.subject human en
dc.title Carbamazepine-resistance in the epileptic dentate gyrus of human hippocampal slices en
dc.type Artigo
dc.contributor.institution Charite Univ Med Berlin
dc.contributor.institution Charles Univ
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Epilepsy Ctr Berlin Brandenburg
dc.description.affiliation Charite Univ Med Berlin, Inst Neurophysiol, D-10117 Berlin, Germany
dc.description.affiliation Charite Univ Med Berlin, Dept Neurosurg, D-10117 Berlin, Germany
dc.description.affiliation Charles Univ, Fac Med 1, Inst Physiol, Prague, Czech Republic
dc.description.affiliation Universidade Federal de São Paulo, Escola Paulista Med, Lab Neurol Expt, São Paulo, Brazil
dc.description.affiliation Epilepsy Ctr Berlin Brandenburg, Berlin, Germany
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Escola Paulista Med, Lab Neurol Expt, São Paulo, Brazil
dc.identifier.doi 10.1093/brain/awl218
dc.description.source Web of Science
dc.identifier.wos WOS:000242471100021


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