title: Inflammatory changes during epileptogenesis and spontaneous seizures in a mouse model of mesiotemporal lobe epilepsy.
abstract: OBJECTIVE
  Neuroinflammation appears as a prominent feature of the mesiotemporal lobe epilepsy syndrome (MTLE) that is observed in human patients and animal models. However, the precise temporal relationship of its development during epileptogenesis remains to be determined. The aim of the present study was to investigate (1) the time course and spatial distribution of neuronal death associated with seizure development, (2) the time course of microglia and astrocyte activation, and (3) the kinetics of induction of mRNAs from neuroinflammatory-related proteins during the emergence of recurrent seizures.
  
  
  METHODS
  Experimental MTLE was induced by the unilateral intrahippocampal injection of kainate in C57BL/6 adult mice. Microglial and astrocytic changes in both ipsilateral and contralateral hippocampi were examined by respectively analyzing griffonia simplicifolia (GSA) lectin staining and glial fibrillary acidic protein (GFAP) immunoreactivity. Changes in mRNA levels of selected genes of cytokine and cytokine regulatory proteins (interleukin-1β, IL-1β; interleukin-1 receptor antagonist, IL-1Ra; suppressor of cytokine signaling 3, SOCS3) and enzymes of the eicosanoid pathway (group IVA cytosolic phospholipase A2, cPLA(2)-α; cycloxygenase-2, COX-2) were studied by reverse transcription-quantitative real time polymerase chain reaction.
  
  
  RESULTS
  Our data show an immediate cell death occurring in the kainate-injected hippocampus during the initial status epilepticus (SE). A rapid increase of activated lectin-positive cells and GFAP-immunoreactivity was subsequently detected in the ipsilateral hippocampus. In the same structure, Il-1β, IL-1Ra, and COX-2 mRNA were specifically increased during SE and epileptogenesis with a different time course. Conversely, the expression of SOCS3 mRNA, a surrogate marker of interleukin signaling, was mainly increased in the contralateral hippocampus after SE.
  
  
  CONCLUSIONS
  Our data show that specific neuroinflammatory pathways are activated in a time- and structure-dependent manner with putative distinct roles in epileptogenesis.
authors.affiliation: Department of Toxicology and Chemical Risks, Institut de Recherche Biomédicale des Armées, Centre de recherches du service de santé des armées, La Tronche Cedex, France. fabien.pernot@gmail.com
authors.forename: Fabien
authors.initials: F
authors.lastname: Pernot
authors.forename: Christophe
authors.initials: C
authors.lastname: Heinrich
authors.forename: Laure
authors.initials: L
authors.lastname: Barbier
authors.forename: André
authors.initials: A
authors.lastname: Peinnequin
authors.forename: Pierre
authors.initials: P
authors.lastname: Carpentier
authors.forename: Franck
authors.initials: F
authors.lastname: Dhote
authors.forename: Valérie
authors.initials: V
authors.lastname: Baille
authors.forename: Claire
authors.initials: C
authors.lastname: Beaup
authors.forename: Antoine
authors.initials: A
authors.lastname: Depaulis
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dorandeu
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000235:genetics / Q000378:metabolism; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000150:complications* / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D037121:Plant Lectins; D012333:RNA, Messenger / Q000378:metabolism; D012640:Seizures / Q000209:etiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
chemical_list: D016207:Cytokines; D015777:Eicosanoids; D005904:Glial Fibrillary Acidic Protein; C045475:Griffonia simplicifolia lectins; D037121:Plant Lectins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D007608:Kainic Acid