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

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.

[1]  Ludwin Sk,et al.  The neuropathology of multiple sclerosis. , 2000 .

[2]  H. Lassmann,et al.  Autoimmunity to Myelin Oligodendrocyte Glycoprotein in Rats Mimics the Spectrum of Multiple Sclerosis Pathology , 1998, Brain pathology.

[3]  H. Lassmann,et al.  Immunopathology of multiple sclerosis: Report on an international meeting held at the Institute of Neurology of the University of Vienna , 1998, Journal of Neuroimmunology.

[4]  H. Lassmann,et al.  Multiple sclerosis: In situ evidence for antibody‐ and complement‐mediated demyelination , 1998, Annals of neurology.

[5]  W. Brück,et al.  Oligodendrocyte and axon pathology in clinically silent multiple sclerosis lesions , 1998, Multiple sclerosis.

[6]  R. Rudick,et al.  Axonal transection in the lesions of multiple sclerosis. , 1998, The New England journal of medicine.

[7]  H. Hartung,et al.  Isolation and characterization of an oligodendrocyte precursor–derived B‐cell epitope in multiple sclerosis , 1998, Annals of neurology.

[8]  ichard,et al.  AXONAL TRANSECTION IN THE LESIONS OF MULTIPLE SCLEROSIS , 1998 .

[9]  M. Esiri,et al.  The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion. , 1997, Brain : a journal of neurology.

[10]  Hans Lassmann,et al.  Pathology and pathogenesis of demyelinating diseases , 1997, Current opinion in neurology.

[11]  G. Wolswijk.  Oligodendrocyte precursor cells in chronic multiple sclerosis lesions , 1997, Multiple sclerosis.

[12]  V. Perry,et al.  Axonal damage in acute multiple sclerosis lesions. , 1997, Brain : a journal of neurology.

[13]  M. Rodriguez,et al.  Indictment of the microglia as the villain in multiple sclerosis , 1997, Neurology.

[14]  J. Antel,et al.  Multiple Sclerosis: Fas Signaling in Oligodendrocyte Cell Death , 1996, The Journal of experimental medicine.

[15]  J. Menonna,et al.  Involvement of the CD95 (APO-1/Fas) receptor/ligand system in multiple sclerosis brain , 1996, The Journal of experimental medicine.

[16]  Moses Rodriguez,et al.  Distinct Patterns of Multiple Sclerosis Pathology Indicates Heterogeneity in Pathogenesis , 1996, Brain pathology.

[17]  W. Blakemore,et al.  Failure to achieve remyelination of demyelinated rat axons following transplantation of glial cells obtained from the adult human brain , 1996, Neuropathology and applied neurobiology.

[18]  G. Kollias,et al.  Spontaneous inflammatory demyelinating disease in transgenic mice showing central nervous system-specific expression of tumor necrosis factor alpha. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Hans Lassmann,et al.  Monocyte/macrophage differentiation in early multiple sclerosis lesions , 1995, Annals of neurology.

[20]  M. Rodriguez,et al.  A monoclonal autoantibody that promotes central nervous system remyelination in a model of multiple sclerosis is a natural autoantibody encoded by germline immunoglobulin genes. , 1995, Journal of immunology.

[21]  K. Jellinger,et al.  Patterns of oligodendroglia pathology in multiple sclerosis. , 1994, Brain : a journal of neurology.

[22]  W. Brück,et al.  Oligodendrocytes in the early course of multiple sclerosis , 1994, Annals of neurology.

[23]  P. Dore‐Duffy,et al.  Expression of immunologically relevant endothelial cell activation antigens on isolated central neurvous system microvessels from patients with multiple sclerosis , 1994, Annals of neurology.

[24]  B. Scheithauer,et al.  Ultrastructure of multiple sclerosis. , 1994, Ultrastructural pathology.

[25]  M. Cuzner,et al.  Cytokine mRNA expression in inflammatory multiple sclerosis lesions: detection by non-radioactive in situ hybridization. , 1993, Cytokine.

[26]  W. Tourtellotte,et al.  On classification of post-mortem multiple sclerosis plaques for neuroscientists , 1993, Journal of Neuroimmunology.

[27]  P. Kelly,et al.  Oligodendrocyte injury is an early event in lesions of multiple sclerosis. , 1993, Mayo Clinic proceedings.

[28]  T Revesz,et al.  Multiple sclerosis. Pathology of recurrent lesions. , 1993, Brain : a journal of neurology.

[29]  B. Engelhardt,et al.  Induction of persistently demyelinated lesions in the rat following the repeated adoptive transfer of encephalitogenic T cells and demyelinating antibody , 1992, Journal of Neuroimmunology.

[30]  M. Freedman,et al.  Peripheral blood γ‐δ T cells lyse fresh human brain—Derived oligodendrocytes , 1991 .

[31]  C. Brosnan,et al.  Cytokine cytotoxicity against oligodendrocytes. Apoptosis induced by lymphotoxin. , 1991, Journal of Immunology.

[32]  C. Brosnan,et al.  Identification of lymphotoxin and tumor necrosis factor in multiple sclerosis lesions. , 1991, The Journal of clinical investigation.

[33]  M. Freedman,et al.  Peripheral blood gamma-delta T cells lyse fresh human brain-derived oligodendrocytes. , 1991, Annals of neurology.

[34]  R. Sobel,et al.  Intercellular adhesion molecule-1 (ICAM-1) in cellular immune reactions in the human central nervous system. , 1990, The American journal of pathology.

[35]  B. Morgan,et al.  Oligodendrocyte susceptibility to injury by T-cell perforin. , 1990, Immunology.

[36]  J. Matthieu,et al.  Myelin/oligodendrocyte glycoprotein expression during development in normal and myelin-deficient mice. , 1990, Developmental neuroscience.

[37]  R. Stocker,et al.  Selective degeneration of oligodendrocytes mediated by reactive oxygen species. , 1990, Free radical research communications.

[38]  H. Lassmann,et al.  Differential Ultrastructural Localization of Myelin Basic Protein, Myelin/Oligodendroglial Glycoprotein, and 2′,3′‐Cyclic Nucleotide 3′‐Phosphodiesterase in the CNS of Adult Rats , 1989, Journal of neurochemistry.

[39]  J. Benjamins,et al.  Multiple sclerosis. Oligodendrocyte proliferation and differentiation in fresh lesions. , 1989, Laboratory investigation; a journal of technical methods and pathology.

[40]  K. Selmaj,et al.  Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro , 1988, Annals of neurology.

[41]  S. Ludwin,et al.  Can oligodendrocytes attached to myelin proliferate? , 1988, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[42]  U. Traugott.  Multiple sclerosis: relevance of Class I and Class II MHC-expressing cells to lesion development , 1987, Journal of Neuroimmunology.

[43]  V. Friedrich,et al.  Myelin‐specific proteolipid protein is expressed in myelinating schwann cells but is not incorporated into myelin sheaths , 1987, Journal of neuroscience research.

[44]  S. Ludwin.  Proliferation of mature oligodendrocytes after trauma to the central nervous system , 1984, Nature.

[45]  E. Reinherz,et al.  Multiple sclerosis Distribution of T cells, T cell subsets and Ia-positive macrophages in lesions of different ages , 1983, Journal of Neuroimmunology.

[46]  Moses Rodriguez,et al.  Persistent infection of oligodendrocytes in Theiler's virus‐induced encephalomyelitis , 1983, Annals of neurology.

[47]  D. Silberberg,et al.  New diagnostic criteria for multiple sclerosis: Guidelines for research protocols , 1983, Annals of neurology.

[48]  Dr. med. Hans Lassmann.  Comparative Neuropathology of Chronic Experimental Allergic Encephalomyelitis and Multiple Sclerosis , 1983, Schriftenreihe Neurologie / Neurology Series.

[49]  L. Scheinberg,et al.  Multiple sclerosis. Oligodendrocyte survival and proliferation in an active established lesion. , 1981, Laboratory investigation; a journal of technical methods and pathology.

[50]  H. Wiśniewski,et al.  Chronic relapsing experimental allergic encephalomyelitis: Morphological sequence of myelin degradation , 1979, Brain Research.

[51]  H. Wiśniewski,et al.  Studies on demyelination by activated lymphocytes in the rabbit eye. II. Antibody-dependent cell-mediated demyelination. , 1977, Journal of immunology.

[52]  J. Prineas,et al.  Pathology of the early lesion in multiple sclerosis. , 1975, Human pathology.

[53]  M. Hart,et al.  Haemorrhagic and perivenous encephalitis: a clinical-pathological review of 38 cases. , 1975, Journal of neurology, neurosurgery, and psychiatry.

[54]  F. Roncaroli,et al.  Neuropathology of multiple sclerosis , 2012 .

[55]  S. Appel,et al.  The application of tissue culture to the study of experimental, “allergic” encephalomyelitis: I. Patterns Of demyelination , 1961 .