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
Intervirologyjournal_title
Intervirologyauthors
Kummerfeld M,Seehusen F,Klein S,Ulrich R,Kreutzer R,Gerhauser I,Herder V,Baumgärtner W,Beineke Adoi
10.1159/000336563subject
Has Abstractpub_date
2012-01-01 00:00:00pages
401-16issue
6eissn
0300-5526issn
1423-0100pii
000336563journal_volume
55pub_type
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