A systems‐level analysis highlights microglial activation as a modifying factor in common epilepsies

The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems‐level analysis.

[1]  S. Sisodiya,et al.  Regional microglial populations in central autonomic brain regions in SUDEP , 2021, Epilepsia.

[2]  D. Bosco,et al.  Microglial depletion aggravates the severity of acute and chronic seizures in mice , 2020, Brain, Behavior, and Immunity.

[3]  Stefan Bonn,et al.  Deep-learning-based cell composition analysis from tissue expression profiles , 2019, bioRxiv.

[4]  Christian Gieger,et al.  Genome-wide mega-analysis identifies 16 loci and highlights diverse biological mechanisms in the common epilepsies , 2018, Nature Communications.

[5]  R. Miles,et al.  Microglial phenotypes in the human epileptic temporal lobe , 2018, Brain : a journal of neurology.

[6]  E. Aronica,et al.  n-3 Docosapentaenoic acid-derived protectin D1 promotes resolution of neuroinflammation and arrests epileptogenesis , 2018, Brain : a journal of neurology.

[7]  Patrice Godard,et al.  A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target , 2018, Nature Communications.

[8]  T. Arumugam,et al.  Recent progress in therapeutic strategies for microglia-mediated neuroinflammation in neuropathologies , 2018, Expert opinion on therapeutic targets.

[9]  S. Hickman,et al.  Microglia in neurodegeneration , 2018, Nature Neuroscience.

[10]  Neda Bernasconi,et al.  Structural brain abnormalities in the common epilepsies assessed in a worldwide ENIGMA study , 2018, Brain : a journal of neurology.

[11]  R. Dingledine,et al.  Commonalities in epileptogenic processes from different acute brain insults: Do they translate? , 2018, Epilepsia.

[12]  Maria Thom,et al.  Histopathological Findings in Brain Tissue Obtained during Epilepsy Surgery , 2017, The New England journal of medicine.

[13]  A. Regev,et al.  Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution , 2017, Cell reports.

[14]  C. Gross,et al.  Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction , 2017, Nature Communications.

[15]  K. Schuurman,et al.  Staining of HLA-DR, Iba1 and CD68 in human microglia reveals partially overlapping expression depending on cellular morphology and pathology , 2017, Journal of Neuroimmunology.

[16]  Neda Bernasconi,et al.  A meta-analysis on progressive atrophy in intractable temporal lobe epilepsy , 2017, Neurology.

[17]  Josemir W Sander,et al.  Epilepsy as a systemic condition: Link with somatic comorbidities , 2017, Acta neurologica Scandinavica.

[18]  P. Striano,et al.  Recent advances in epilepsy genetics , 2017, Neuroscience Letters.

[19]  M. Zucchetti,et al.  Blockade of the IL-1R1/TLR4 pathway mediates disease-modification therapeutic effects in a model of acquired epilepsy , 2017, Neurobiology of Disease.

[20]  Michael R. Johnson,et al.  Rare and common epilepsies converge on a shared gene regulatory network providing opportunities for novel antiepileptic drug discovery , 2016, Genome Biology.

[21]  Teresa Domaszewska,et al.  tmod: an R package for general and multivariate enrichment analysis , 2016 .

[22]  R. Kuzniecky,et al.  Transient and chronic seizure‐induced inflammation in human focal epilepsy , 2016, Epilepsia.

[23]  Josemir W Sander,et al.  Outcome of seizures in the general population after 25 years: a prospective follow-up, observational cohort study , 2016, Journal of Neurology, Neurosurgery & Psychiatry.

[24]  M. Ryten,et al.  Brain iron accumulation affects myelin-related molecular systems implicated in a rare neurogenetic disease family with neuropsychiatric features , 2016, Molecular Psychiatry.

[25]  Doug Speed,et al.  Systems genetics identifies a convergent gene network for cognition and neurodevelopmental disease , 2015, Nature Neuroscience.

[26]  J. McNamara,et al.  A Peptide Uncoupling BDNF Receptor TrkB from Phospholipase Cγ1 Prevents Epilepsy Induced by Status Epilepticus , 2015, Neuron.

[27]  Allan R. Jones,et al.  Canonical Genetic Signatures of the Adult Human Brain , 2015, Nature Neuroscience.

[28]  P. Deyn,et al.  Brain inflammation in a chronic epilepsy model: Evolving pattern of the translocator protein during epileptogenesis , 2015, Neurobiology of Disease.

[29]  Leon French,et al.  A FreeSurfer view of the cortical transcriptome generated from the Allen Human Brain Atlas , 2015, Front. Neurosci..

[30]  Kimberly J. Jenko,et al.  Neuroinflammation in Temporal Lobe Epilepsy Measured Using Positron Emission Tomographic Imaging of Translocator Protein. , 2015, JAMA neurology.

[31]  Jeremy A. Miller,et al.  Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis , 2015, Acta Neuropathologica Communications.

[32]  Brian L. West,et al.  Colony-Stimulating Factor 1 Receptor Signaling Is Necessary for Microglia Viability, Unmasking a Microglia Progenitor Cell in the Adult Brain , 2014, Neuron.

[33]  R. Andrews,et al.  Innate Immune Activity Conditions the Effect of Regulatory Variants upon Monocyte Gene Expression , 2014, Science.

[34]  L. Tran,et al.  Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease , 2013, Cell.

[35]  Orrin Devinsky,et al.  Glia and epilepsy: excitability and inflammation , 2013, Trends in Neurosciences.

[36]  Rosamund F Langston,et al.  Lateral Entorhinal Cortex is Critical for Novel Object-Context Recognition , 2013, Hippocampus.

[37]  V. Perry,et al.  Review: Activation patterns of microglia and their identification in the human brain , 2013, Neuropathology and applied neurobiology.

[38]  Allan R. Jones,et al.  An anatomically comprehensive atlas of the adult human brain transcriptome , 2012, Nature.

[39]  Donncha F. O’Brien,et al.  Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects , 2012, Nature Medicine.

[40]  K. Nakken,et al.  Importance of genetic factors in the occurrence of epilepsy syndrome type: A twin study , 2011, Epilepsy Research.

[41]  S. Horvath,et al.  Transcriptomic Analysis of Autistic Brain Reveals Convergent Molecular Pathology , 2011, Nature.

[42]  Maria Thom,et al.  Investigation of widespread neocortical pathology associated with hippocampal sclerosis in epilepsy: A postmortem study , 2011, Epilepsia.

[43]  P. V. van Rijen,et al.  Evaluation of the innate and adaptive immunity in type I and type II focal cortical dysplasias , 2010, Epilepsia.

[44]  Eleonora Aronica,et al.  Innate and adaptive immunity during epileptogenesis and spontaneous seizures: Evidence from experimental models and human temporal lobe epilepsy , 2008, Neurobiology of Disease.

[45]  E. Aronica,et al.  The IL-1β system in epilepsy-associated malformations of cortical development , 2006, Neurobiology of Disease.

[46]  E. Aronica,et al.  Evidence of activated microglia in focal cortical dysplasia , 2006, Journal of Neuroimmunology.

[47]  P. V. van Rijen,et al.  Distribution, characterization and clinical significance of microglia in glioneuronal tumours from patients with chronic intractable epilepsy , 2005, Neuropathology and applied neurobiology.

[48]  A. James Barkovich,et al.  Malformations of cortical development and epilepsy , 2001, Brain and Development.

[49]  T. Michoel,et al.  Microglial brain regiondependent diversity and selective regional sensitivities to aging , 2015 .