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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.
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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