Periventricular demyelination and axonal pathology is associated with subependymal virus spread in a murine model for multiple sclerosis.

Abstract:

OBJECTIVES: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.

journal_name

Intervirology

journal_title

Intervirology

authors

Kummerfeld M,Seehusen F,Klein S,Ulrich R,Kreutzer R,Gerhauser I,Herder V,Baumgärtner W,Beineke A

doi

10.1159/000336563

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

401-16

issue

6

eissn

0300-5526

issn

1423-0100

pii

000336563

journal_volume

55

pub_type

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