title: Periventricular demyelination and axonal pathology is associated with subependymal virus spread in a murine model for multiple sclerosis.
abstract: OBJECTIVE
  Theiler's murine encephalomyelitis virus (TMEV) infection of mice is a widely used animal model for demyelinating disorders, such as multiple sclerosis (MS). The aim of the present study was to identify topographical differences of TMEV spread and demyelination in the brain of experimentally infected susceptible SJL/J mice and resistant C57BL/6 mice.
  
  
  METHODS
  Demyelination was confirmed by Luxol fast blue and cresyl violet staining and axonal damage by neurofilament-specific and β-amyloid precursor protein-specific immunohistochemistry. Viral dissemination within the central nervous system (CNS) was quantified by immunohistochemistry and in situ hybridization. Further, the phenotype of infected cells was determined by confocal laser scanning microscopy.
  
  
  RESULTS
  An early transient infection of periventricular cells followed by demyelination and axonopathies around the fourth ventricle in SJL/J mice was noticed. Periventricular and brain stem demyelination was associated with a predominant infection of microglia/macrophages and oligodendrocytes.
  
  
  CONCLUSIONS
  Summarized, the demonstration of ependymal infection and subjacent spread into the brain parenchyma as well as regional virus clearance despite ongoing demyelination and axonal damage in other CNS compartments allows new insights into TME pathogenesis. This novel aspect of TMEV CNS interaction will enhance the understanding of region-specific susceptibilities to injury and regenerative capacities of the brain in this MS model.
authors.affiliation: Department of Pathology, University of Veterinary Medicine Hanover, Hanover, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: Kummerfeld
authors.forename: Frauke
authors.initials: F
authors.lastname: Seehusen
authors.forename: Stephanie
authors.initials: S
authors.lastname: Klein
authors.forename: Reiner
authors.initials: R
authors.lastname: Ulrich
authors.forename: Robert
authors.initials: R
authors.lastname: Kreutzer
authors.forename: Ingo
authors.initials: I
authors.lastname: Gerhauser
authors.forename: Vanessa
authors.initials: V
authors.lastname: Herder
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Baumgärtner
authors.forename: Andreas
authors.initials: A
authors.lastname: Beineke
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000737:chemistry; D000818:Animals; D001369:Axons / Q000473:pathology; D001921:Brain / Q000473:pathology / Q000821:virology; D018188:Cardiovirus Infections / Q000473:pathology* / Q000821:virology; D003711:Demyelinating Diseases / Q000473:pathology* / Q000821:virology; D004195:Disease Models, Animal; D004805:Ependyma / Q000473:pathology* / Q000821:virology; D005260:Female; D008264:Macrophages / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000473:pathology*; D009836:Oligodendroglia / Q000821:virology; D017945:Theilovirus / Q000472:pathogenicity*
chemical_list: D016564:Amyloid beta-Protein Precursor