Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Ann Neurol ; 76(3): 428-42, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25074818

RESUMO

OBJECTIVE: Subcortical band heterotopia (SBH) is a cortical malformation formed when neocortical neurons prematurely stop their migration in the white matter, forming a heterotopic band below the normotopic cortex, and is generally associated with intractable epilepsy. Although it is clear that the band heterotopia and the overlying cortex both contribute to creating an abnormal circuit prone to generate epileptic discharges, it is less understood which part of this circuitry is the most critical. Here, we sought to identify the origin of epileptiform activity in a targeted genetic model of SBH in rats. METHODS: Rats with SBH (Dcx-KD rats) were generated by knocking down the Dcx gene using shRNA vectors transfected into neocortical progenitors of rat embryos. Origin, spatial extent, and laminar profile of bicuculline-induced interictal-like activity on neocortical slices were analyzed by using extracellular recordings from 60-channel microelectrode arrays. Susceptibility to pentylenetetrazole-induced seizures was assessed by electrocorticography in head-restrained nonanesthetized rats. RESULTS: We show that the band heterotopia does not constitute a primary origin for interictal-like epileptiform activity in vitro and is dispensable for generating induced seizures in vivo. Furthermore, we report that most interictal-like discharges originating in the overlying cortex secondarily propagate to the band heterotopia. Importantly, we found that in vivo suppression of neuronal excitability in SBH does not alter the higher propensity of Dcx-KD rats to display seizures. INTERPRETATION: These results suggest a major role of the normotopic cortex over the band heterotopia in generating interictal epileptiform activity and seizures in brains with SBH.


Assuntos
Córtex Cerebral/fisiopatologia , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/fisiopatologia , Epilepsia/etiologia , Epilepsia/fisiopatologia , Neocórtex/fisiopatologia , Animais , Bicuculina/farmacologia , Córtex Cerebral/efeitos dos fármacos , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/complicações , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/patologia , Convulsivantes/farmacologia , Modelos Animais de Doenças , Proteínas do Domínio Duplacortina , Proteína Duplacortina , Eletroencefalografia , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Fenômenos Eletrofisiológicos/fisiologia , Epilepsia/induzido quimicamente , Técnicas de Silenciamento de Genes , Proteínas Associadas aos Microtúbulos/genética , Neocórtex/efeitos dos fármacos , Rede Nervosa/anormalidades , Rede Nervosa/fisiopatologia , Neuropeptídeos/genética , Pentilenotetrazol/farmacologia , Ratos , Ratos Transgênicos , Convulsões/induzido quimicamente , Convulsões/fisiopatologia , Córtex Somatossensorial/efeitos dos fármacos , Córtex Somatossensorial/fisiopatologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA