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Updated: Jul 26, 2025
Isolation of Mouse Primary Microglia by Magnetic-Activated Cell Sorting in Animal Models of Demyelination
Published on: April 5, 2022
Microglia subtypes in acute, subacute, and chronic multiple sclerosis
1Department of Medicine, The University of Sydney, Camperdown, NSW, Australia.
Abstract:
The study was designed to examine microglia morphology in early and late forms of multiple sclerosis (MS). Archival paraffin embedded tissue samples from 25 cases were examined immunohistochemically. Pío del Río Hortega reported that phagocytes in acute focal destructive CNS lesions develop from microglia with no early contribution from infiltrating monocytes. In this study, we were unable to identify the changes cited by del Río Hortega in support of his theory. Instead, myelin phagocytes in MS appear to originate chiefly from infiltrating monocytes. In 4 cases, walls composed of MHC class II antigen-positive "wall microglia" were observed at plaque margins separating demyelinated and bordering myelinated tissue. Wall microglia in 2 plaques were accompanied by AQP4-positive fiber-forming astrocytes. In chronic but not early disease MS cases, microglia were seen to interact with infiltrating monocytes to form microglial nodules of several types. Also, MHC II-positive "activated" microglia in bordering intact tissue were exceptionally prominent where there was little evidence of ongoing myelin loss. It is concluded that myelin phagocytes in MS derive entirely from infiltrating MRP14-positive monocytes and not from resident microglia and that Río Hortega's microglia play an anti-inflammatory role in MS and not the destructive role favored by the current literature.
Insights
Myelin phagocytes in multiple sclerosis (MS) originate from infiltrating monocytes, not resident microglia. Río Hortega's microglia appear to have an anti-inflammatory role in MS, contrary to current literature.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglia are the resident immune cells of the central nervous system (CNS).
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS.
- The origin of myelin phagocytes in MS lesions has been debated, with Pío del Río Hortega proposing microglia as the primary source.
Purpose of the Study:
- To investigate microglia morphology in early and late stages of multiple sclerosis (MS).
- To determine the origin of myelin phagocytes in MS lesions.
- To clarify the role of microglia in the pathogenesis of MS.
Main Methods:
- Immunohistochemical examination of archival paraffin-embedded tissue samples from 25 MS cases.
- Analysis of microglia morphology and interaction with other immune cells.
- Identification of specific cellular markers, including MHC class II and MRP14.
Main Results:
- Myelin phagocytes in MS lesions were found to originate primarily from infiltrating monocytes, not resident microglia.
- "Wall microglia" expressing MHC class II were observed at plaque margins, sometimes associated with astrocytes.
- Microglial nodules formed by interactions between microglia and monocytes were present in chronic MS, and "activated" microglia were prominent in areas without active demyelination.
Conclusions:
- Myelin phagocytes in MS are derived entirely from infiltrating MRP14-positive monocytes.
- Resident microglia, as described by Río Hortega, appear to play an anti-inflammatory role in MS.
- These findings challenge the traditional view of microglia having a destructive role in MS pathogenesis.
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