A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases

Claudia F Lucchinetti, Wolfgang Brück, Joseph E Parisi, Bernd Scheithauer, Moses Rodriguez, Hans Lassmann

Research output: Contribution to journalArticle

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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). To 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.

Original languageEnglish (US)
Pages (from-to)2279-2295
Number of pages17
JournalBrain
Volume122
Issue number12
DOIs
StatePublished - Dec 1999

Fingerprint

Oligodendroglia
Multiple Sclerosis
Myelin-Oligodendrocyte Glycoprotein
Proteolipids
Pathology
Myelin Sheath
Messenger RNA
Oligodendrocyte-Myelin Glycoprotein
Proteins
Demyelinating Diseases
Plasma Cells
Autopsy
Catalytic Domain

Keywords

  • Demyelination
  • Multiple sclerosis
  • Oligodendrocytes
  • Pathology

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Lucchinetti, C. F., Brück, W., Parisi, J. E., Scheithauer, B., Rodriguez, M., & Lassmann, H. (1999). A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. Brain, 122(12), 2279-2295. https://doi.org/10.1093/brain/122.12.2279

A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. / Lucchinetti, Claudia F; Brück, Wolfgang; Parisi, Joseph E; Scheithauer, Bernd; Rodriguez, Moses; Lassmann, Hans.

In: Brain, Vol. 122, No. 12, 12.1999, p. 2279-2295.

Research output: Contribution to journalArticle

Lucchinetti, CF, Brück, W, Parisi, JE, Scheithauer, B, Rodriguez, M & Lassmann, H 1999, 'A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases', Brain, vol. 122, no. 12, pp. 2279-2295. https://doi.org/10.1093/brain/122.12.2279
Lucchinetti, Claudia F ; Brück, Wolfgang ; Parisi, Joseph E ; Scheithauer, Bernd ; Rodriguez, Moses ; Lassmann, Hans. / A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. In: Brain. 1999 ; Vol. 122, No. 12. pp. 2279-2295.
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