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Cited by 16Multiple Sclerosis Research StudiesNeuroinflammation and Neurodegeneration MechanismsInflammasome and immune disorders

Microglia subtypes in acute, subacute, and chronic multiple sclerosis

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Prineas, John W, Lee, Sandra·2023·Journal of Neuropathology & Experimental Neurology
DOI 10.1093/jnen/nlad046PMC PMC10357941
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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.

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  • In cortical grey matter, oligodendrocyte recruitment and remyelination is an early phenomenon in MS lesion formation that occurs in the immediate post-phagocytic phase when foam cells are still abundant in demyelinated lesions.

    “For cortical grey matter, this now indicates that oligodendrocyte recruitment and remyelination is an early phenomenon in MS lesion formation that occurs in the immediate post-phagocytic phase when foam cells are still abundant in the demyelinated lesions.56-60”

    From BCAS1-positive oligodendrocytes enable efficient cortical remyelination in multiple sclerosis (2025) · cites this paper as [60]

    The Results sections on foamy macrophages and subacute MS report remyelination in recently demyelinated tissue alongside foamy macrophages, and oligodendrocyte precursors in recently demyelinated and postphagocytic plaques. They do not establish that this sequence occurs specifically in cortical grey matter or confine it to the immediate post-phagocytic phase. Page numbers are unavailable in our copy. (LLM, conf=0.85)

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Authors
Prineas, J. W., & Lee, S.
Affiliations
The University of Sydney (AU)
Corresponding author
Prineas, John W
ORCID
Prineas, John W
Venue
Journal of Neuropathology & Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
2023-06-21
Volume
82
Issue
8
Pages
674-694
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
DOI
10.1093/jnen/nlad046
PMC
PMC10357941
OpenAlex
W4381599059
Cited by
16
References
8
Citations by year
2026: 5 · 2025: 4 · 2024: 7
FWCI
3.19
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Multiple Sclerosis Research Australia
  • Nerve Research Foundation
  • University of Sydney
  • National Multiple Sclerosis Society (JWP RG 2731-A-B)
  • NSW Ministry for Science and Medical Research
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords
multiple sclerosis, microglial morphology, infiltrating monocytes, S100A9, MHC class II, activated microglia, microglial nodules, demyelination, Pío del Río-Hortega
MeSH terms
Humans, Monocytes, Multiple Sclerosis, Myelin Sheath, Nervous System Diseases, Phagocytes, Microglia

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