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Analysis of the transcriptome of brain tissue from epilepsy patients with focal cortical dysplasia or mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE)

Abstract

Epilepsy is a neurological disease characterized by recurrent unprovoked seizures. Individuals who are refractory to medications may be candidates to surgical treatment. Malformation of cortical development (MCD), a common cause of refractory epilepsy, corresponds to a wide range of lesions including focal cortical dysplasia (FCD). Classical histopathological findings observed in FCD specimens are dysmorphic neurons associated or not with balloon cells (FCD Type IIa or IIb, respectively according to the 2011 International League Against Epilepsy (ILAE) Classification). Despite functional preoperative findings (clinical, electrophysiological and/or neuroimaging) suggestive of FCD, neuropathological evaluation of the resected tissue does not always allow a precise identification of an abnormal histological pattern characteristic of FCD. Thus, it may be identified only non-specific minor changes with debatable physiopathological and/or prognostic relevance. Particularly, a virtual increase in the white matter oligodendroglial population associated with blurring of the grey and white matter boundary have been defined as "malformation of cortical development with oligodendroglial hyperplasia" (MOGHE). Therefore, in this context of discordance between functional alterations and a corresponding resected tissue with discrete alterations, new research to find biomarkers indicative of a dysfunctional brain region is relevant. Here, we propose (1) the use of transcriptome analysis to identify differentially expressed mRNAs and (2) posterior immunohistochemical assessment of the distribution and expression of the codified proteins in the same tissue of FCDIIa, FCDIIb or suggestive MOGHE samples. Since transcriptome analysis allows a vast mapping of both abundantly and scantily expressed mRNAs, the use of this technique is useful to simultaneously evaluate a wide range of molecular pathways that might be abnormally regulated in brain samples with or without a conclusive histopathological diagnosis. Specifically, the RNA-Seq technology will be used for the first time to perform the transcriptome analyses of Brazilian and German patients to investigate new biomarkers of epilepsy-related brain dysfunction, response to surgical treatment and/or prognosis. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
MENDES COELHO, VANESSA C.; MORITA-SHERMAN, MARCIA; YASUDA, CLARISSA L.; ALVIM, MARINA M. K.; AMORIM, BARBARA JUAREZ; TEDESCHI, HELDER; GHIZONI, ENRICO; ROGERIO, FABIO; CENDES, FERNANDO. Magnetic resonance imaging findings and clinical characteristics in mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy in a predominantly adult cohort. Epilepsia, v. 62, n. 6, . (19/08259-0, 13/07559-3)
ZAIDAN, BRUNA CUNHA; CARDOSO, INGRID CAROLINA DA SILVA; DE CAMPOS, BRUNNO MACHADO; DA SILVA, LUCIANA RAMALHO PIMENTEL; COELHO, VANESSA C. MENDES; SILVEIRA, KAIRO ALEXANDRE ALVES; AMORIM, BARBARA JUAREZ; ALVIM, MARINA KOUTSODONTIS MACHADO; TEDESCHI, HELDER; YASUDA, CLARISSA LIN; et al. Histopathological Correlations of Qualitative and Quantitative Temporopolar MRI Analyses in Patients With Hippocampal Sclerosis. FRONTIERS IN NEUROLOGY, v. 12, . (19/08259-0, 20/12651-0)

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