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Spontaneous epileptiform activity in a rat model of bilateral subcortical band heterotopia
Author(s) -
Sahu Surajit,
Buhler Emmanuelle,
Vermoyal JeanChristophe,
Watrin Françoise,
Represa Alfonso,
Manent JeanBernard
Publication year - 2019
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.14633
Subject(s) - epilepsy , neuroscience , magnetoencephalography , ethosuximide , electroencephalography , medicine , epileptogenesis , psychology , phenytoin
Summary 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 RNA i‐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 ( SWD s) with dominant frequencies in the alpha and theta bands and secondarily in higher‐frequency bands. SWD s occurred during both the dark and the light period, but were more frequent during quiet awake state than during sleep. Also, SWD s were more frequent and lasted longer at older ages. No sex differences were found. Although frequencies and durations of SWD s were found to be uncorrelated with the size of SBH , SWD s were initiated in some occasions from brain hemispheres comprising a larger SBH . Lastly, SWD s 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.