Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement

Lawrence S Hsieh; John H Wen; Kumiko Claycomb; Yuegao Huang; Felicia A Harrsch; Janice R Naegele; Fahmeed Hyder; Gordon F Buchanan; Angelique Bordey

doi:10.1038/ncomms11753

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Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement

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Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement

Lawrence S Hsieh, John H Wen, Kumiko Claycomb, Yuegao Huang, Felicia A Harrsch, Janice R Naegele, Fahmeed Hyder, Gordon F Buchanan and Angelique Bordey

Nature communications, Vol.7(1), pp.11753-11753

06/01/2016

DOI: 10.1038/ncomms11753

PMCID: PMC4895394

PMID: 27249187

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Abstract

Focal cortical dysplasia (FCD), a local malformation of cortical development, is the most common cause of pharmacoresistant epilepsy associated with life-long neurocognitive impairments. It remains unclear whether neuronal misplacement is required for seizure activity. Here we show that dyslamination and white matter heterotopia are not necessary for seizure generation in a murine model of type II FCDs. These experimental FCDs generated by increasing mTOR activity in layer 2/3 neurons of the medial prefrontal cortex are associated with tonic-clonic seizures and a normal survival rate. Preventing all FCD-related defects, including neuronal misplacement and dysmorphogenesis, with rapamycin treatments from birth eliminates seizures, but seizures recur after rapamycin withdrawal. In addition, bypassing neuronal misplacement and heterotopia using inducible vectors do not prevent seizure occurrence. Collectively, data obtained using our new experimental FCD-associated epilepsy suggest that life-long treatment to reduce neuronal dysmorphogenesis is required to suppress seizures in individuals with FCD.

Details

Title: Subtitle: Convulsive seizures from experimental focal cortical dysplasia occur independently of cell misplacement
Creators: Lawrence S Hsieh - Departments of Neurosurgery, and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA
John H Wen - Departments of Neurosurgery, and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA
Kumiko Claycomb - Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA
Yuegao Huang - Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA
Felicia A Harrsch - Department of Biology, Wesleyan University, Middletown, Connecticut 06459, USA
Janice R Naegele - Department of Biology, Wesleyan University, Middletown, Connecticut 06459, USA
Fahmeed Hyder - Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA
Gordon F Buchanan - Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA
Angelique Bordey - Departments of Neurosurgery, and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA
Resource Type: Journal article
Publication Details: Nature communications, Vol.7(1), pp.11753-11753
DOI: 10.1038/ncomms11753
PMID: 27249187
PMCID: PMC4895394
NLM abbreviation: Nat Commun
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: England
Grant note: R15 NS072879 / NINDS NIH HHS R21 NS093510 / NINDS NIH HHS K08 NS069667 / NINDS NIH HHS P30 NS052519 / NINDS NIH HHS R01 MH067528 / NIMH NIH HHS
Language: English
Date published: 06/01/2016
Academic Unit: Neurology; Iowa Neuroscience Institute
Record Identifier: 9984020644802771

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