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- Title
Periventricular Demyelination and Axonal Pathology Is Associated with Subependymal Virus Spread in a Murine Model for Multiple Sclerosis.
- Authors
Kummerfeld, Maren; Seehusen, Frauke; Klein, Stephanie; Ulrich, Reiner; Kreutzer, Robert; Gerhauser, Ingo; Herder, Vanessa; Baumgartner, Wolfgang; Beineke, Andreas
- Abstract
Objectives: Theiler's murine encephalomyelitis virus (TMEV) infection of mice is a widely used animal model for demyelin-ating 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 experi-mentally 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 (3-amyloid precursor protein-specific immunohistochemistry. Viral dissemination within the central nervous system (CNS) was quantified by immu-nohistochemistry and in situ hybridization. Further, the phe-notype of infected cells was determined by confocal laser scanning microscopy. Results: An early transient infection of periventricular cells followed by demyelination and axonop-athies 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 dem-onstration 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 pathogen-esis. This novel aspect of TMEV CNS interaction will enhance the understanding of region-specific susceptibilities to in-jury and regenerative capacities of the brain in this MS model.
- Subjects
DEMYELINATION; AXONS; MULTIPLE sclerosis; DISEASE susceptibility; THEILER'S murine encephalomyelitis virus; LABORATORY mice
- Publication
Intervirology, 2012, Vol 55, Issue 6, p401
- ISSN
0300-5526
- Publication type
Article
- DOI
10.1159/000336563