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Cited by 464Multiple Sclerosis Research StudiesNeurogenesis and neuroplasticity mechanismsNeuroinflammation and Neurodegeneration Mechanisms

A quantitative analysis of oligodendrocytes in multiple sclerosis lesions

Lucchinetti, Claudia, Brück, Wolfgang, Parisi, Joseph, Scheithauer, Bernd, Rodriguez, Moses, Lassmann, Hans·1999·Brain
DOI 10.1093/brain/122.12.2279
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Abstract

We studied quantitatively the fate of oligodendrocytes (OGs) during lesion formation in 395 lesion areas from biopsy and autopsy tissue of 113 multiple sclerosis cases. The density of OGs in multiple sclerosis lesions was variable at all stages of demyelinating activity, ranging from nearly complete loss to values exceeding those in the periplaque white matter (range 0-970 OGs/mm2) determine whether there were distinct patterns of OG pathology in different patients, we restricted our analysis to the 56 cases in which the longitudinal extent of the lesion extended from periplaque white matter into the active demyelinating edge and inactive plaque centre. Two major groups of OG pathology were defined by the presence or absence of increased OGs within the lesion. In 70% (39 out of 56) of the cases, OGs were variably reduced during active stages of myelin destruction, but reappeared within inactive or remyelinating areas. In inactive areas, an increased number of OGs expressing proteolipid protein (PLP) mRNA compared with those expressing myelin oligodendrocyte glycoprotein (MOG) suggested these cells may have been derived from the progenitor pool. In the remaining 30% (17 out of 56) of the cases, extensive destruction of myelinating cells at active sites of demyelination was observed, but OGs were absent in inactive plaque areas without remyelination. In all lesions from a given patient the pattern of OG pathology remained consistent. A highly significant negative correlation was observed between number of macrophages in lesions and number of MOG- and PLP mRNA-labelled OGs (MOG: r = -0.32, P < 0.0000118; PLP mRNA: r = -0.23, P < 0.00238). OG density did not correlate with T-cell and plasma cell inflammation, or axonal loss. The profound heterogeneity in extent and topography of OG destruction in active demyelinating lesions suggests that in subsets of multiple sclerosis patients, myelin, mature OGs and possibly OG progenitors are differentially affected.

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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 [58]

    The ‘Consequences for remyelination’ section (page unavailable) says remyelination can be extensive early in the formation of some MS lesions and correlates with oligodendrocytes in the lesions. The copy does not establish this specifically for cortical grey matter or place recruitment and remyelination in an immediate post-phagocytic phase while foam cells remain abundant. (LLM, conf=0.85)

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Cited by

Sorted by citations

Authors
Lucchinetti, C., Brück, W., Parisi, J., Scheithauer, B., Rodriguez, M., & Lassmann, H.
Affiliations
  • Mayo Clinic (US)
  • Medical University of Vienna (AT)
Corresponding author
Lucchinetti, Claudia
ORCID
Venue
Brain
Publisher
Oxford University Press (OUP)
Published
1999-12
Volume
122
Issue
12
Pages
2279-2295
ISSN
  • 0006-8950 (ISSN-L)
  • 1460-2156
DOI
10.1093/brain/122.12.2279
OpenAlex
W2098589841
Cited by
464
References
2
Citations by year
2026: 6 · 2025: 10 · 2024: 6 · 2023: 9 · 2022: 15 · 2021: 11 · 2020: 13 · 2019: 28 · 2018: 20 · 2017: 13 · 2016: 12 · 2015: 17 · 2014: 18 · 2013: 22 · 2012: 20
FWCI
14.41
Type
journal article
Language
en
Open access
closed
Locations
  • Brain (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Mayo Foundation for Medical Education and Research
  • Gemeinnützige Hertie-Stiftung
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
multiple sclerosis, oligodendrocytes, demyelination, oligodendrocyte loss, remyelination, myelin oligodendrocyte glycoprotein, oligodendrocyte progenitors, macrophages, plaque heterogeneity, myelin destruction
MeSH terms
Adult, Cell Count, Female, Humans, Macrophages, Male, Middle Aged, Multiple Sclerosis, Myelin Proteins, Oligodendroglia, RNA, Messenger, Myelin Proteolipid Protein, Myelin-Associated Glycoprotein, Myelin-Oligodendrocyte Glycoprotein

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