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 ()
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Lawrence S. Hsieh: and Cellular and Molecular Physiology, Yale University School of Medicine
John H. Wen: and Cellular and Molecular Physiology, Yale University School of Medicine
Kumiko Claycomb: Yale University School of Medicine
Yuegao Huang: Magnetic Resonance Research Center, Yale University School of Medicine
Felicia A. Harrsch: Wesleyan University
Janice R. Naegele: Wesleyan University
Fahmeed Hyder: Magnetic Resonance Research Center, Yale University School of Medicine
Gordon F. Buchanan: Yale University School of Medicine
Angelique Bordey: and Cellular and Molecular Physiology, Yale University School of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: 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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11753

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DOI: 10.1038/ncomms11753

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