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Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines
Published on: September 21, 2021
Periventricular demyelination and axonal pathology is associated with subependymal virus spread in a murine model for
Maren Kummerfeld1, Frauke Seehusen, Stephanie Klein
1Department of Pathology, University of Veterinary Medicine Hanover, Hanover, Germany.
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.
Insights
Theiler
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Theiler's murine encephalomyelitis virus (TMEV) infection in mice serves as a key animal model for studying demyelinating diseases like multiple sclerosis (MS).
- Understanding the topographical differences in viral spread and subsequent demyelination is crucial for advancing MS research.
Purpose of the Study:
- To investigate and delineate the topographical distinctions in TMEV spread and demyelination within the brains of susceptible SJL/J and resistant C57BL/6 mice.
- To characterize the cellular phenotype of infected cells and the extent of axonal damage during TMEV infection.
Main Methods:
- Histological analysis using Luxol fast blue and cresyl violet staining for demyelination.
- Immunohistochemistry and in situ hybridization to quantify viral dissemination in the central nervous system (CNS).
- Confocal laser scanning microscopy to determine the phenotype of infected cells.
Main Results:
- SJL/J mice exhibited early, transient periventricular cell infection, followed by demyelination and axonopathies near the fourth ventricle.
- Periventricular and brain stem demyelination correlated with significant infection of microglia/macrophages and oligodendrocytes.
Conclusions:
- TMEV infection reveals ependymal spread into the brain parenchyma with regional virus clearance, offering new insights into Theiler's Murine Encephalomyelitis pathogenesis.
- These findings enhance understanding of region-specific brain injury susceptibilities and regenerative capacities within this MS model.
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