title: Axonal expression of sodium channels and neuropathology of the plaques in multiple sclerosis.
abstract: OBJECTIVE
  Although demyelination is an important cause of neurological deficits in multiple sclerosis (MS), recently axonal pathology and concomitant involvement of sodium channels (Nav) became a focus of major interest. Studies in experimental autoimmune encephalomyelitis (EAE) and MS have shown diffuse expression of Nav1.6 and Nav1.2 along demyelinated axons. However, the relation between this expression by the axon and its environment is not yet known. The aim of this exploratory study was to identify the neuropathological characteristics of the plaque associated with the changes of sodium channel axonal expression.
  
  
  METHODS
  We analysed by immunohistochemistry the expression of Nav1.6 and Nav1.2 along demyelinated axons in 64 plaques from 12 MS cases. To characterize the plaques, we used Luxol fast blue staining and immunohistochemistry for myelin basic protein, microglia/macrophages, T and B cells, reactive astrocytes and axonal lesions performed on sections of formalin-fixed, paraffin-embedded tissue.
  
  
  RESULTS
  The presence of diffuse axonal expression of Nav1.6 was equally distributed between active demyelinating and inactive not demyelinating plaques based on presence or absence of myelin laden macrophages respectively. However, presence of diffuse axonal expression of Nav1.6 was more frequent within plaques with T cells infiltrate and microglial hyperplasia. On the other hand, Nav1.2 diffuse axonal expression seemed to be independent of the neuropathological environment of the plaque.
  
  
  CONCLUSIONS
  The cellular environment of the axon influences the differential expression of Nav channels. A better understanding of the influence of the inflammation on sodium channels mediated axonal degeneration could offer therapeutic perspectives.
authors: Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière (CRICM), INSERM UMR_S975, CNRS UMR7225, UPMC-Sorbonne Universités, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors: Adel
authors: A
authors: Bouafia
authors: Jean-Louis
authors: JL
authors: Golmard
authors: Valerie
authors: V
authors: Thuries
authors: Veronique
authors: V
authors: Sazdovitch
authors: Jean Jacques
authors: JJ
authors: Hauw
authors: Betrand
authors: B
authors: Fontaine
authors: Danielle
authors: D
authors: Seilhean
mesh_terms: D000328:Adult; D000368:Aged; D001369:Axons / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology*; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000378:metabolism*; D062557:NAV1.6 Voltage-Gated Sodium Channel / Q000378:metabolism*
chemical_list: D062551:NAV1.2 Voltage-Gated Sodium Channel; D062557:NAV1.6 Voltage-Gated Sodium Channel
keywords: T cells; active demyelinating; inactive not demyelinating; microglial hyperplasia; multiple sclerosis; sodium channels