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Spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia

OBJECTIVE: Malformations of cortical development are common causes of intellectual disability and epilepsy, yet there is a crucial lack of relevant preclinical models associating seizures and cortical malformations. Here, we describe a novel rat model with bilateral subcortical band heterotopia (SBH...

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Autores principales: Sahu, Surajit, Buhler, Emmanuelle, Vermoyal, Jean‐Christophe, Watrin, Françoise, Represa, Alfonso, Manent, Jean‐Bernard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027481/
https://www.ncbi.nlm.nih.gov/pubmed/30597542
http://dx.doi.org/10.1111/epi.14633
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author Sahu, Surajit
Buhler, Emmanuelle
Vermoyal, Jean‐Christophe
Watrin, Françoise
Represa, Alfonso
Manent, Jean‐Bernard
author_facet Sahu, Surajit
Buhler, Emmanuelle
Vermoyal, Jean‐Christophe
Watrin, Françoise
Represa, Alfonso
Manent, Jean‐Bernard
author_sort Sahu, Surajit
collection PubMed
description OBJECTIVE: Malformations of cortical development are common causes of intellectual disability and epilepsy, yet there is a crucial lack of relevant preclinical models associating seizures and cortical malformations. Here, we describe a novel rat model with bilateral subcortical band heterotopia (SBH) and examine whether this model develops spontaneous epileptic seizures. METHODS: To generate bilateral SBH in rats, we combined RNAi‐mediated knockdown of Dcx and in utero electroporation with a tripolar electrode configuration enabling simultaneous transfection of the two brain hemispheres. To determine whether bilateral SBH leads to epileptiform activity, rats of various ages were implanted for telemetric electrocorticographic recordings and histopathological examination was carried out at the end of the recording sessions. RESULTS: By 2 months, rats with bilateral SBH showed nonconvulsive spontaneous seizures consisting of spike‐and‐wave discharges (SWDs) with dominant frequencies in the alpha and theta bands and secondarily in higher‐frequency bands. SWDs occurred during both the dark and the light period, but were more frequent during quiet awake state than during sleep. Also, SWDs were more frequent and lasted longer at older ages. No sex differences were found. Although frequencies and durations of SWDs were found to be uncorrelated with the size of SBH, SWDs were initiated in some occasions from brain hemispheres comprising a larger SBH. Lastly, SWDs exhibited absence‐like pharmacological properties, being temporarily alleviated by ethosuximide administration. SIGNIFICANCE: This novel model of bilateral SBH with spontaneous epilepsy may potentially provide valuable new insights into causality between cortical malformations and seizures, and help translational research aiming at designing novel treatment strategies for epilepsy.
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spelling pubmed-70274812020-02-24 Spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia Sahu, Surajit Buhler, Emmanuelle Vermoyal, Jean‐Christophe Watrin, Françoise Represa, Alfonso Manent, Jean‐Bernard Epilepsia Full‐length Original Research OBJECTIVE: Malformations of cortical development are common causes of intellectual disability and epilepsy, yet there is a crucial lack of relevant preclinical models associating seizures and cortical malformations. Here, we describe a novel rat model with bilateral subcortical band heterotopia (SBH) and examine whether this model develops spontaneous epileptic seizures. METHODS: To generate bilateral SBH in rats, we combined RNAi‐mediated knockdown of Dcx and in utero electroporation with a tripolar electrode configuration enabling simultaneous transfection of the two brain hemispheres. To determine whether bilateral SBH leads to epileptiform activity, rats of various ages were implanted for telemetric electrocorticographic recordings and histopathological examination was carried out at the end of the recording sessions. RESULTS: By 2 months, rats with bilateral SBH showed nonconvulsive spontaneous seizures consisting of spike‐and‐wave discharges (SWDs) with dominant frequencies in the alpha and theta bands and secondarily in higher‐frequency bands. SWDs occurred during both the dark and the light period, but were more frequent during quiet awake state than during sleep. Also, SWDs were more frequent and lasted longer at older ages. No sex differences were found. Although frequencies and durations of SWDs were found to be uncorrelated with the size of SBH, SWDs were initiated in some occasions from brain hemispheres comprising a larger SBH. Lastly, SWDs exhibited absence‐like pharmacological properties, being temporarily alleviated by ethosuximide administration. SIGNIFICANCE: This novel model of bilateral SBH with spontaneous epilepsy may potentially provide valuable new insights into causality between cortical malformations and seizures, and help translational research aiming at designing novel treatment strategies for epilepsy. John Wiley and Sons Inc. 2018-12-30 2019-02 /pmc/articles/PMC7027481/ /pubmed/30597542 http://dx.doi.org/10.1111/epi.14633 Text en © 2018 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Full‐length Original Research
Sahu, Surajit
Buhler, Emmanuelle
Vermoyal, Jean‐Christophe
Watrin, Françoise
Represa, Alfonso
Manent, Jean‐Bernard
Spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia
title Spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia
title_full Spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia
title_fullStr Spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia
title_full_unstemmed Spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia
title_short Spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia
title_sort spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia
topic Full‐length Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027481/
https://www.ncbi.nlm.nih.gov/pubmed/30597542
http://dx.doi.org/10.1111/epi.14633
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