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Updated: Apr 19, 2026
Three-dimensional Confocal Analysis of Microglia/macrophage Markers of Polarization in Experimental Brain Injury
Published on: September 4, 2013
Dynamic Changes of Microglia/Macrophage M1 and M2 Polarization in Theiler's Murine Encephalomyelitis
Vanessa Herder1,2, Cut Dahlia Iskandar1,2, Kristel Kegler1,2
1Department of Pathology, University of Veterinary Medicine Hannover, Hannover, Germany.
Abstract:
Microglia and macrophages play a central role for demyelination in Theiler's murine encephalomyelitis (TME) virus infection, a commonly used infectious model for chronic-progressive multiple sclerosis. In order to determine the dynamic changes of microglia/macrophage polarization in TME, the spinal cord of Swiss Jim Lambert (SJL) mice was investigated by gene expression profiling and immunofluorescence. Virus persistence and demyelinating leukomyelitis were confirmed by immunohistochemistry and histology. Electron microscopy revealed continuous myelin loss together with abortive myelin repair during the late chronic infection phase indicative of incomplete remyelination. A total of 59 genes out of 151 M1- and M2-related genes were differentially expressed in TME virus-infected mice over the study period. The onset of virus-induced demyelination was associated with a dominating M1 polarization, while mounting M2 polarization of macrophages/microglia together with sustained prominent M1-related gene expression was present during the chronic-progressive phase. Molecular results were confirmed by immunofluorescence, showing an increased spinal cord accumulation of CD16/32(+) M1-, arginase-1(+) M2- and Ym1(+) M2-type cells associated with progressive demyelination. The present study provides a comprehensive database of M1-/M2-related gene expression involved in the initiation and progression of demyelination supporting the hypothesis that perpetuating interaction between virus and macrophages/microglia induces a vicious circle with persistent inflammation and impaired myelin repair in TME.
Insights
Microglia and macrophages drive demyelination in Theiler's murine encephalomyelitis (TME) virus infection. M1 polarization initiates disease, while M2 polarization with persistent M1 activity impairs myelin repair during chronic stages.
Area of Science:
- Neuroimmunology
- Virology
- Pathology
Background:
- Theiler's murine encephalomyelitis (TME) virus infection is a model for chronic-progressive multiple sclerosis.
- Microglia and macrophages are key players in demyelination during TME virus infection.
Purpose of the Study:
- To investigate the dynamic changes in microglia/macrophage polarization during TME virus infection.
- To understand the role of M1 and M2 polarization in demyelination and impaired myelin repair.
Main Methods:
- Gene expression profiling of M1/M2-related genes in mouse spinal cords.
- Immunofluorescence to identify M1 and M2 cell populations.
- Immunohistochemistry, histology, and electron microscopy to assess viral persistence, demyelination, and myelin repair.
Main Results:
- A total of 59 differentially expressed genes related to M1 and M2 polarization were identified.
- M1 polarization dominated during the onset of demyelination.
- M2 polarization increased during the chronic phase, alongside sustained M1 gene expression, correlating with progressive demyelination and incomplete myelin repair.
Conclusions:
- The study provides a gene expression database for M1/M2 polarization in TME virus-induced demyelination.
- Persistent interaction between the virus and microglia/macrophages creates a cycle of inflammation and impaired myelin repair.
