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Demyelination and Remyelination in Multiple Sclerosis

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Myelin Repair and Neuroprotection in Multiple Sclerosis

Abstract

The defining trait of multiple sclerosis (MS) histopathology is the presence of spatially separate focal areas of demyelination (called MS lesions, or plaques) of different age and inflammatory activity in the central nervous system (CNS). Although the nature and cause of the initial MS lesion change are not known, recent years have seen major advances in our understanding of MS pathology and pathogenesis. The aim of this review is to give a brief account of the histopathology of demyelination and remyelination in MS, with an emphasis on some issues of current interest in MS pathology research, including MS lesion staging, pathological heterogeneity, gray matter pathology, and axonal loss.

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References

  • Aarli JA, Aparicio SR, Lumsden CE, Tonder O (1975) Binding of normal human IgG to myelin sheaths, glia and neurons. Immunology 28:171–185

    PubMed  CAS  Google Scholar 

  • Albert M, Antel J, Bruck W, Stadelmann C (2007) Extensive cortical remyelination in patients with chronic multiple sclerosis. Brain Pathol 17:129–138

    PubMed  Google Scholar 

  • Arnett HA, Mason J, Marino M, Suzuki K, Matsushima GK, Ting JP (2001) TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination. Nat Neurosci 4:1116–1122

    PubMed  CAS  Google Scholar 

  • Back SA, Tuohy TM, Chen H, Wallingford N, Craig A, Struve J, Luo NL, Banine F, Liu Y, Chang A, Trapp BD, Bebo BF Jr, Rao MS, Sherman LS (2005) Hyaluronan accumulates in demyelinated lesions and inhibits oligodendrocyte progenitor maturation. Nat Med 11:966–972

    PubMed  CAS  Google Scholar 

  • Barkhof F, Bruck W, De Groot CJ, Bergers E, Hulshof S, Geurts J, Polman CH, van der Valk P (2003) Remyelinated lesions in multiple sclerosis: magnetic resonance image appearance. Arch Neurol 60:1073–1081

    PubMed  Google Scholar 

  • Barnes D, Munro PM, Youl BD, Prineas JW, McDonald WI (1991) The longstanding MS lesion. A quantitative MRI and electron microscopic study. Brain 114(Pt 3):1271–1280

    PubMed  Google Scholar 

  • Barnett MH, Prineas JW (2004) Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol 55:458–468

    PubMed  Google Scholar 

  • Bitsch A, Schuchardt J, Bunkowski S, Kuhlmann T, Bruck W (2000) Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain 123(Pt 6):1174–1183

    PubMed  Google Scholar 

  • Black JA, Newcombe J, Trapp BD, Waxman SG (2007) Sodium channel expression within chronic multiple sclerosis plaques. J Neuropathol Exp Neurol 66:828–837

    PubMed  CAS  Google Scholar 

  • Bo L, Mork S, Kong PA, Nyland H, Pardo CA, Trapp BD (1994) Detection of MHC class II-antigens on macrophages and microglia, but not on astrocytes and endothelia in active multiple sclerosis lesions. J Neuroimmunol 51:135–146

    PubMed  CAS  Google Scholar 

  • Bo L, Vedeler CA, Nyland H, Trapp BD, Mork SJ (2003a) Intracortical multiple sclerosis lesions are not associated with increased lymphocyte infiltration. Mult Scler 9:323–331

    PubMed  CAS  Google Scholar 

  • Bo L, Vedeler CA, Nyland HI, Trapp BD, Mork SJ (2003b) Subpial demyelination in the cerebral cortex of multiple sclerosis patients. J Neuropathol Exp Neurol 62:723–732

    PubMed  Google Scholar 

  • Bo L, Geurts JJ, van der Valk P, Polman C, Barkhof F (2007) Lack of correlation between cortical demyelination and white matter pathologic changes in multiple sclerosis. Arch Neurol 64: 76–80

    PubMed  Google Scholar 

  • Bramow S, Frischer JM, Lassmann H, Koch-Henriksen N, Lucchinetti CF, Sorensen PS, Laursen H (2010) Demyelination versus remyelination in progressive multiple sclerosis. Brain 133:2983–2998

    PubMed  Google Scholar 

  • Breij EC, Brink BP, Veerhuis R, van den Berg C, Vloet R, Yan R, Dijkstra CD, van der Valk P, Bo L (2008) Homogeneity of active demyelinating lesions in established multiple sclerosis. Ann Neurol 63:16–25

    PubMed  CAS  Google Scholar 

  • Brink BP, Veerhuis R, Breij EC, van der Valk P, Dijkstra CD, Bo L (2005) The pathology of multiple sclerosis is location-dependent: no significant complement activation is detected in purely cortical lesions. J Neuropathol Exp Neurol 64:147–155

    PubMed  CAS  Google Scholar 

  • Brown WJ (1978) The capillaries in acute and subacute multiple sclerosis plaques: a morphometric analysis. Neurology 28:84–92

    PubMed  CAS  Google Scholar 

  • Bruck W, Porada P, Poser S et al. (1995) Monocyte/macrophage differentiation in early multiple sclerosis lesions. Ann Neurol 38:788–796

    PubMed  CAS  Google Scholar 

  • Chang A, Tourtellotte WW, Rudick R, Trapp BD (2002) Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med 346:165–173

    PubMed  Google Scholar 

  • Chang A, Smith MC, Yin X, Fox RJ, Staugaitis SM, Trapp BD (2008) Neurogenesis in the chronic lesions of multiple sclerosis. Brain 131:2366–2375

    PubMed  Google Scholar 

  • Chari DM, Zhao C, Kotter MR, Blakemore WF, Franklin RJ (2006) Corticosteroids delay remyelination of experimental demyelination in the rodent central nervous system. J Neurosci Res 83:594–605

    PubMed  CAS  Google Scholar 

  • Charles P, Hernandez MP, Stankoff B, Aigrot MS, Colin C, Rougon G, Zalc B, Lubetzki C (2000) Negative regulation of central nervous system myelination by polysialylated-neural cell adhesion molecule. Proc Natl Acad Sci USA 97:7585–7590

    PubMed  CAS  Google Scholar 

  • Charles P, Reynolds R, Seilhean D, Rougon G, Aigrot MS, Niezgoda A, Zalc B, Lubetzki C (2002) Re-expression of PSA-NCAM by demyelinated axons: an inhibitor of remyelination in multiple sclerosis? Brain 125:1972–1979

    PubMed  Google Scholar 

  • Confavreux C, Vukusic S (2006) Natural history of multiple sclerosis: a unifying concept. Brain 129:606–616

    PubMed  Google Scholar 

  • Craner MJ, Lo AC, Black JA, Waxman SG (2003) Abnormal sodium channel distribution in optic nerve axons in a model of inflammatory demyelination. Brain 126:1552–1561

    PubMed  Google Scholar 

  • Davie CA, Hawkins CP, Barker GJ, Brennan A, Tofts PS, Miller DH, McDonald WI (1994) Serial proton magnetic resonance spectroscopy in acute multiple sclerosis lesions. Brain 117(Pt 1): 49–58

    PubMed  Google Scholar 

  • Dawson JW (1916) The histology of multiple sclerosis. Trans R Soc Edinb 50:517–740

    Google Scholar 

  • Dziedzic T, Metz I, Dallenga T, Konig FB, Muller S, Stadelmann C, Bruck W (2010) Wallerian degeneration: a major component of early axonal pathology in multiple sclerosis. Brain Pathol 20:976–985

    PubMed  Google Scholar 

  • Esiri MM (1977) Immunoglobulin-containing cells in multiple-sclerosis plaques. Lancet 2:478

    PubMed  CAS  Google Scholar 

  • Evangelou N, Esiri MM, Smith S, Palace J, Matthews PM (2000a) Quantitative pathological evidence for axonal loss in normal appearing white matter in multiple sclerosis. Ann Neurol 47:391–395

    PubMed  CAS  Google Scholar 

  • Evangelou N, Konz D, Esiri MM, Smith S, Palace J, Matthews PM (2000b) Regional axonal loss in the corpus callosum correlates with cerebral white matter lesion volume and distribution in multiple sclerosis. Brain 123(Pt 9):1845–1849

    PubMed  Google Scholar 

  • Evangelou N, Konz D, Esiri MM, Smith S, Palace J, Matthews PM (2001) Size-selective neuronal changes in the anterior optic pathways suggest a differential susceptibility to injury in multiple sclerosis. Brain 124:1813–1820

    PubMed  CAS  Google Scholar 

  • Fancy SP, Zhao C, Franklin RJ (2004) Increased expression of Nkx2.2 and Olig2 identifies reactive oligodendrocyte progenitor cells responding to demyelination in the adult CNS. Mol Cell Neurosci 27:247–254

    PubMed  CAS  Google Scholar 

  • Fancy SP, Baranzini SE, Zhao C, Yuk DI, Irvine KA, Kaing S, Sanai N, Franklin RJ, Rowitch DH (2009) Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS. Genes Dev 23:1571–1585

    PubMed  CAS  Google Scholar 

  • Ferguson B, Matyszak MK, Esiri MM, Perry VH (1997) Axonal damage in acute multiple sclerosis lesions. Brain 120(Pt 3):393–399

    PubMed  Google Scholar 

  • Frohman EM, Racke MK, Raine CS (2006) Multiple sclerosis – the plaque and its pathogenesis. N Engl J Med 354:942–955

    PubMed  CAS  Google Scholar 

  • Gay FW, Drye TJ, Dick GW, Esiri MM (1997) The application of multifactorial cluster analysis in the staging of plaques in early multiple sclerosis. Identification and characterization of the primary demyelinating lesion. Brain 120(Pt 8):1461–1483

    PubMed  Google Scholar 

  • Geurts JJ, Bo L, Pouwels PJ, Castelijns JA, Polman CH, Barkhof F (2005) Cortical lesions in multiple sclerosis: combined postmortem MR imaging and histopathology. AJNR Am J Neuroradiol 26:572–577

    PubMed  Google Scholar 

  • Geurts JJ, Bo L, Roosendaal SD, Hazes T, Daniels R, Barkhof F, Witter MP, Huitinga I, van der Valk P (2007) Extensive hippocampal demyelination in multiple sclerosis. J Neuropathol Exp Neurol 66:819–827

    PubMed  Google Scholar 

  • Gilmore CP, Donaldson I, Bo L, Owens T, Lowe J, Evangelou N (2009) Regional variations in the extent and pattern of grey matter demyelination in multiple sclerosis: a comparison between the cerebral cortex, cerebellar cortex, deep grey matter nuclei and the spinal cord. J Neurol Neurosurg Psychiatry 80:182–187

    PubMed  CAS  Google Scholar 

  • Gilson J, Blakemore WF (1993) Failure of remyelination in areas of demyelination produced in the spinal cord of old rats. Neuropathol Appl Neurobiol 19:173–181

    PubMed  CAS  Google Scholar 

  • Goldschmidt T, Antel J, Konig FB, Bruck W, Kuhlmann T (2009) Remyelination capacity of the MS brain decreases with disease chronicity. Neurology 72:1914–1921

    PubMed  CAS  Google Scholar 

  • Green AJ, McQuaid S, Hauser SL, Allen IV, Lyness R (2010) Ocular pathology in multiple sclerosis: retinal atrophy and inflammation irrespective of disease duration. Brain 133:1591–1601

    PubMed  Google Scholar 

  • Groves AK, Barnett SC, Franklin RJ, Crang AJ, Mayer M, Blakemore WF, Noble M (1993) Repair of demyelinated lesions by transplantation of purified O-2A progenitor cells. Nature 362:453–455

    PubMed  CAS  Google Scholar 

  • Guo YP, Gao SF (1983) Concentric sclerosis. Clin Exp Neurol 19:67–76

    PubMed  CAS  Google Scholar 

  • Gutowski NJ, Newcombe J, Cuzner ML (1999) Tenascin-R and C in multiple sclerosis lesions: relevance to extracellular matrix remodelling. Neuropathol Appl Neurobiol 25:207–214

    PubMed  CAS  Google Scholar 

  • Hoftberger R, Aboul-Enein F, Brueck W, Lucchinetti C, Rodriguez M, Schmidbauer M, Jellinger K, Lassmann H (2004) Expression of major histocompatibility complex class I molecules on the different cell types in multiple sclerosis lesions. Brain Pathol 14:43–50

    PubMed  CAS  Google Scholar 

  • Hu QD, Ang BT, Karsak M, Hu WP, Cui XY, Duka T, Takeda Y, Chia W, Sankar N, Ng YK, Ling EA, Maciag T, Small D, Trifonova R, Kopan R, Okano H, Nakafuku M, Chiba S, Hirai H, Aster JC, Schachner M, Pallen CJ, Watanabe K, Xiao ZC (2003) F3/contactin acts as a functional ligand for Notch during oligodendrocyte maturation. Cell 115:163–175

    PubMed  CAS  Google Scholar 

  • Jarjour AA, Kennedy TE (2004) Oligodendrocyte precursors on the move: mechanisms directing migration. Neuroscientist 10:99–105

    PubMed  Google Scholar 

  • John GR, Shankar SL, Shafit-Zagardo B, Massimi A, Lee SC, Raine CS, Brosnan CF (2002) Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat Med 8:1115–1121

    PubMed  CAS  Google Scholar 

  • Keirstead HS, Blakemore WF (1997) Identification of post-mitotic oligodendrocytes incapable of remyelination within the demyelinated adult spinal cord. J Neuropathol Exp Neurol 56:1191–1201

    PubMed  CAS  Google Scholar 

  • Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R (1999) Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med 189:865–870

    PubMed  CAS  Google Scholar 

  • Kooi EJ, Geurts JJ, van Horssen J, Bo L, van der Valk P (2009) Meningeal inflammation is not associated with cortical demyelination in chronic multiple sclerosis. J Neuropathol Exp Neurol 68:1021–1028

    PubMed  CAS  Google Scholar 

  • Kotter MR, Zhao C, van Rooijen N, Franklin RJ (2005) Macrophage-depletion induced impairment of experimental CNS remyelination is associated with a reduced oligodendrocyte progenitor cell response and altered growth factor expression. Neurobiol Dis 18:166–175

    PubMed  CAS  Google Scholar 

  • Kuhlmann T, Miron V, Cui Q, Wegner C, Antel J, Bruck W (2008) Differentiation block of oligodendroglial progenitor cells as a cause for remyelination failure in chronic multiple sclerosis. Brain 131:1749–1758

    PubMed  CAS  Google Scholar 

  • Kutzelnigg A, Lucchinetti CF, Stadelmann C, Bruck W, Rauschka H, Bergmann M, Schmidbauer M, Parisi JE, Lassmann H (2005) Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain 128:2705–2712

    PubMed  Google Scholar 

  • Kutzelnigg A, Faber-Rod JC, Bauer J, Lucchinetti CF, Sorensen PS, Laursen H, Stadelmann C, Bruck W, Rauschka H, Schmidbauer M, Lassmann H (2007) Widespread demyelination in the cerebellar cortex in multiple sclerosis. Brain Pathol 17:38–44

    PubMed  Google Scholar 

  • Kwon EE, Prineas JW (1994) Blood-brain barrier abnormalities in longstanding multiple sclerosis lesions. An immunohistochemical study. J Neuropathol Exp Neurol 53:625–636

    PubMed  CAS  Google Scholar 

  • Lassmann H (1983) Comparative neuropathology of chronic experimental allergic encephalomyelitis and multiple sclerosis. Schriftenr Neurol 25:1–135

    PubMed  CAS  Google Scholar 

  • Lassmann H, Raine CS, Antel J, Prineas JW (1998) Immunopathology of multiple sclerosis: report on an international meeting held at the Institute of Neurology of the University of Vienna. J Neuroimmunol 86:213–217

    PubMed  CAS  Google Scholar 

  • Lassmann H, Niedobitek G, Aloisi F, Middeldorp JM (2011) Epstein-Barr virus in the multiple sclerosis brain: a controversial issue – report on a focused workshop held in the Centre for Brain Research of the Medical University of Vienna, Austria. Brain 134:2772–2786

    PubMed  Google Scholar 

  • Levine JM, Reynolds R (1999) Activation and proliferation of endogenous oligodendrocyte precursor cells during ethidium bromide-induced demyelination. Exp Neurol 160:333–347

    PubMed  CAS  Google Scholar 

  • Li WW, Penderis J, Zhao C, Schumacher M, Franklin RJ (2006) Females remyelinate more efficiently than males following demyelination in the aged but not young adult CNS. Exp Neurol 202:250–254

    PubMed  CAS  Google Scholar 

  • Liu L, Darnall L, Hu T, Choi K, Lane TE, Ransohoff RM (2010) Myelin repair is accelerated by inactivating CXCR2 on nonhematopoietic cells. J Neurosci 30:9074–9083

    PubMed  CAS  Google Scholar 

  • Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (1999) A quantitative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. Brain 122(Pt 12):2279–2295

    PubMed  Google Scholar 

  • Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (2000) Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 47:707–717

    PubMed  CAS  Google Scholar 

  • Lucchinetti CF, Popescu BF, Bunyan RF, Moll NM, Roemer SF, Lassmann H, Bruck W, Parisi JE, Scheithauer BW, Giannini C, Weigand SD, Mandrekar J, Ransohoff RM (2011) Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med 365:2188–2197

    PubMed  CAS  Google Scholar 

  • Magliozzi R, Howell O, Vora A, Serafini B, Nicholas R, Puopolo M, Reynolds R, Aloisi F (2007) Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 130:1089–1104

    PubMed  Google Scholar 

  • Marburg O (1906) Die sogenannte “akute multiple sklerose” (encephalomyelitis periaxialis scleroticans). J Psychiatr Neurol 27: 217–312

    Google Scholar 

  • Marin-Husstege M, Muggironi M, Liu A, Casaccia-Bonnefil P (2002) Histone deacetylase activity is necessary for oligodendrocyte lineage progression. J Neurosci 22:10333–10345

    PubMed  CAS  Google Scholar 

  • Marret S, Delpech B, Delpech A, Asou H, Girard N, Courel MN, Chauzy C, Maingonnat C, Fessard C (1994) Expression and effects of hyaluronan and of the hyaluronan-binding protein hyaluronectin in newborn rat brain glial cell cultures. J Neurochem 62:1285–1295

    PubMed  CAS  Google Scholar 

  • Moll NM, Rietsch AM, Ransohoff AJ, Cossoy MB, Huang D, Eichler FS, Trapp BD, Ransohoff RM (2008) Cortical demyelination in PML and MS: similarities and differences. Neurology 70:336–343

    PubMed  CAS  Google Scholar 

  • Nait-Oumesmar B, Picard-Riera N, Kerninon C, Decker L, Seilhean D, Hoglinger GU, Hirsch EC, Reynolds R, Baron-Van Evercooren A (2007) Activation of the subventricular zone in multiple sclerosis: evidence for early glial progenitors. Proc Natl Acad Sci USA 104:4694–4699

    PubMed  CAS  Google Scholar 

  • Nakahara J, Kanekura K, Nawa M, Aiso S, Suzuki N (2009) Abnormal expression of TIP30 and arrested nucleocytoplasmic transport within oligodendrocyte precursor cells in multiple sclerosis. J Clin Invest 119:169–181

    PubMed  CAS  Google Scholar 

  • Ozawa K, Suchanek G, Breitschopf H, Bruck W, Budka H, Jellinger K, Lassmann H (1994) Patterns of oligodendroglia pathology in multiple sclerosis. Brain 117(Pt 6):1311–1322

    PubMed  Google Scholar 

  • Papadopoulos D, Dukes S, Patel R, Nicholas R, Vora A, Reynolds R (2009) Substantial archaeocortical atrophy and neuronal loss in multiple sclerosis. Brain Pathol 19:238–253

    PubMed  Google Scholar 

  • Patani R, Balaratnam M, Vora A, Reynolds R (2007) Remyelination can be extensive in multiple sclerosis despite a long disease course. Neuropathol Appl Neurobiol 33:277–287

    PubMed  CAS  Google Scholar 

  • Patrikios P, Stadelmann C, Kutzelnigg A, Rauschka H, Schmidbauer M, Laursen H, Sorensen PS, Bruck W, Lucchinetti C, Lassmann H (2006) Remyelination is extensive in a subset of multiple sclerosis patients. Brain 129:3165–3172

    PubMed  Google Scholar 

  • Pedre X, Mastronardi F, Bruck W, Lopez-Rodas G, Kuhlmann T, Casaccia P (2011) Changed histone acetylation patterns in normal-appearing white matter and early multiple sclerosis lesions. J Neurosci 31:3435–3445

    PubMed  CAS  Google Scholar 

  • Perier O, Gregoire A (1965) Electron microscopic features of multiple sclerosis lesions. Brain 88:937–952

    PubMed  CAS  Google Scholar 

  • Peterson JW, Bo L, Mork S, Chang A, Trapp BD (2001) Transected neurites, apoptotic neurons, and reduced inflammation in cortical multiple sclerosis lesions. Ann Neurol 50:389–400

    PubMed  CAS  Google Scholar 

  • Piaton G, Aigrot MS, Williams A, Moyon S, Tepavcevic V, Moutkine I, Gras J, Matho KS, Schmitt A, Soellner H, Huber AB, Ravassard P, Lubetzki C (2011) Class 3 semaphorins influence oligodendrocyte precursor recruitment and remyelination in adult central nervous system. Brain 134:1156–1167

    PubMed  Google Scholar 

  • Plumb J, McQuaid S, Mirakhur M, Kirk J (2002) Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis. Brain Pathol 12:154–169

    PubMed  Google Scholar 

  • Pohl HB, Porcheri C, Mueggler T, Bachmann LC, Martino G, Riethmacher D, Franklin RJ, Rudin M, Suter U (2011) Genetically induced adult oligodendrocyte cell death is associated with poor myelin clearance, reduced remyelination, and axonal damage. J Neurosci 31:1069–1080

    PubMed  CAS  Google Scholar 

  • Prineas JW, Connell F (1978) The fine structure of chronically active multiple sclerosis plaques. Neurology 28:68–75

    PubMed  CAS  Google Scholar 

  • Prineas JW, Connell F (1979) Remyelination in multiple sclerosis. Ann Neurol 5:22–31

    PubMed  CAS  Google Scholar 

  • Prineas JW, Graham JS (1981) Multiple sclerosis: capping of surface immunoglobulin G on macrophages engaged in myelin breakdown. Ann Neurol 10:149–158

    PubMed  CAS  Google Scholar 

  • Prineas JW, Barnard RO, Kwon EE, Sharer LR, Cho ES (1993a) Multiple sclerosis: remyelination of nascent lesions. Ann Neurol 33:137–151

    PubMed  CAS  Google Scholar 

  • Prineas JW, Barnard RO, Revesz T, Kwon EE, Sharer L, Cho ES (1993b) Multiple sclerosis. Pathology of recurrent lesions. Brain 116(Pt 3):681–693

    PubMed  Google Scholar 

  • Raine CS, Wu E (1993) Multiple sclerosis: remyelination in acute lesions. J Neuropathol Exp Neurol 52:199–204

    PubMed  CAS  Google Scholar 

  • Revesz T, Kidd D, Thompson AJ, Barnard RO, McDonald WI (1994) A comparison of the pathology of primary and secondary progressive multiple sclerosis. Brain 117(Pt 4):759–765

    PubMed  Google Scholar 

  • Rodriguez M, Scheithauer B (1994) Ultrastructure of multiple sclerosis. Ultrastruct Pathol 18:3–13

    PubMed  CAS  Google Scholar 

  • Sanders V, Conrad AJ, Tourtellotte WW (1993) On classification of post-mortem multiple sclerosis plaques for neuroscientists. J Neuroimmunol 46:207–216

    PubMed  CAS  Google Scholar 

  • Schonrock LM, Kuhlmann T, Adler S, Bitsch A, Bruck W (1998) Identification of glial cell proliferation in early multiple sclerosis lesions. Neuropathol Appl Neurobiol 24:320–330

    PubMed  CAS  Google Scholar 

  • Seewann A, Vrenken H, Kooi EJ, van der Valk P, Knol DL, Polman CH, Pouwels PJ, Barkhof F, Geurts JJ (2011) Imaging the tip of the iceberg: visualization of cortical lesions in multiple sclerosis. Mult Scler 17:1202–1210

    PubMed  Google Scholar 

  • Serafini B, Rosicarelli B, Magliozzi R, Stigliano E, Aloisi F (2004) Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 14:164–174

    PubMed  Google Scholar 

  • Shen S, Li J, Casaccia-Bonnefil P (2005) Histone modifications affect timing of oligodendrocyte progenitor differentiation in the developing rat brain. J Cell Biol 169:577–589

    PubMed  CAS  Google Scholar 

  • Shen S, Sandoval J, Swiss VA, Li J, Dupree J, Franklin RJ, Casaccia-Bonnefil P (2008) Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency. Nat Neurosci 11:1024–1034

    PubMed  CAS  Google Scholar 

  • Shields SA, Gilson JM, Blakemore WF, Franklin RJ (1999) Remyelination occurs as extensively but more slowly in old rats compared to young rats following gliotoxin-induced CNS demyelination. Glia 28:77–83

    PubMed  CAS  Google Scholar 

  • Shimizu T, Kagawa T, Wada T, Muroyama Y, Takada S, Ikenaka K (2005) Wnt signaling controls the timing of oligodendrocyte development in the spinal cord. Dev Biol 282:397–410

    PubMed  CAS  Google Scholar 

  • Sim FJ, Zhao C, Penderis J, Franklin RJ (2002) The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J Neurosci 22:2451–2459

    PubMed  CAS  Google Scholar 

  • Sloane JA, Batt C, Ma Y, Harris ZM, Trapp B, Vartanian T (2010) Hyaluronan blocks oligodendrocyte progenitor maturation and remyelination through TLR2. Proc Natl Acad Sci USA 107:11555–11560

    PubMed  CAS  Google Scholar 

  • Sobel RA, Chen M, Maeda A, Hinojoza JR (1995) Vitronectin and integrin vitronectin receptor localization in multiple sclerosis lesions. J Neuropathol Exp Neurol 54:202–213

    PubMed  CAS  Google Scholar 

  • Stadelmann C, Kerschensteiner M, Misgeld T, Bruck W, Hohlfeld R, Lassmann H (2002) BDNF and gp145trkB in multiple sclerosis brain lesions: neuroprotective interactions between immune and neuronal cells? Brain 125:75–85

    PubMed  Google Scholar 

  • Syed YA, Hand E, Mobius W, Zhao C, Hofer M, Nave KA, Kotter MR (2011) Inhibition of CNS remyelination by the presence of semaphorin 3A. J Neurosci 31:3719–3728

    PubMed  CAS  Google Scholar 

  • Tallantyre EC, Bo L, Al-Rawashdeh O, Owens T, Polman CH, Lowe J, Evangelou N (2009) Greater loss of axons in primary progressive multiple sclerosis plaques compared to secondary progressive disease. Brain 132:1190–1199

    PubMed  CAS  Google Scholar 

  • Targett MP, Sussman J, Scolding N, O’Leary MT, Compston DA, Blakemore WF (1996) Failure to achieve remyelination of demyelinated rat axons following transplantation of glial cells obtained from the adult human brain. Neuropathol Appl Neurobiol 22:199–206

    PubMed  CAS  Google Scholar 

  • Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L (1998) Axonal transection in the lesions of multiple sclerosis. N Engl J Med 338:278–285

    PubMed  CAS  Google Scholar 

  • van der Goes A, Boorsma W, Hoekstra K, Montagne L, de Groot CJ, Dijkstra CD (2005) Determination of the sequential degradation of myelin proteins by macrophages. J Neuroimmunol 161:12–20

    PubMed  Google Scholar 

  • van der Valk P, De Groot CJ (2000) Staging of multiple sclerosis (MS) lesions: pathology of the time frame of MS. Neuropathol Appl Neurobiol 26:2–10

    PubMed  Google Scholar 

  • van Horssen J, Brink BP, de Vries HE, van der Valk P, Bo L (2007) The blood-brain barrier in cortical multiple sclerosis lesions. J Neuropathol Exp Neurol 66:321–328

    PubMed  Google Scholar 

  • Vercellino M, Plano F, Votta B, Mutani R, Giordana MT, Cavalla P (2005) Grey matter pathology in multiple sclerosis. J Neuropathol Exp Neurol 64:1101–1107

    PubMed  Google Scholar 

  • Watanabe M, Toyama Y, Nishiyama A (2002) Differentiation of proliferated NG2-positive glial progenitor cells in a remyelinating lesion. J Neurosci Res 69:826–836

    PubMed  CAS  Google Scholar 

  • Williams A, Piaton G, Aigrot MS, Belhadi A, Theaudin M, Petermann F, Thomas JL, Zalc B, Lubetzki C (2007) Semaphorin 3A and 3F: key players in myelin repair in multiple sclerosis? Brain 130:2554–2565

    PubMed  Google Scholar 

  • Wolswijk G (1998a) Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J Neurosci 18:601–609

    PubMed  CAS  Google Scholar 

  • Wolswijk G (1998b) Oligodendrocyte regeneration in the adult rodent CNS and the failure of this process in multiple sclerosis. Prog Brain Res 117:233–247

    PubMed  CAS  Google Scholar 

  • Wolswijk G (2000) Oligodendrocyte survival, loss and birth in lesions of chronic-stage multiple sclerosis. Brain 123(Pt 1):105–115

    PubMed  Google Scholar 

  • Wolswijk G (2002) Oligodendrocyte precursor cells in the demyelinated multiple sclerosis spinal cord. Brain 125:338–349

    PubMed  Google Scholar 

  • Ye F, Chen Y, Hoang T, Montgomery RL, Zhao XH, Bu H, Hu T, Taketo MM, van Es JH, Clevers H, Hsieh J, Bassel-Duby R, Olson EN, Lu QR (2009) HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the beta-catenin-TCF interaction. Nat Neurosci 12:829–838

    PubMed  CAS  Google Scholar 

  • Young EA, Fowler CD, Kidd GJ, Chang A, Rudick R, Fisher E, Trapp BD (2008) Imaging correlates of decreased axonal Na+/K+ ATPase in chronic multiple sclerosis lesions. Ann Neurol 63:428–435

    PubMed  Google Scholar 

  • Zhang SC, Ge B, Duncan ID (1999) Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity. Proc Natl Acad Sci USA 96:4089–4094

    PubMed  CAS  Google Scholar 

  • Zhang Y, et al. (2009) Notch1 signaling plays a role in regulating precursor differentiation during CNS remyelination. Proc Natl Acad Sci USA 106:19162–19167

    PubMed  Google Scholar 

Download references

Acknowledgements

Prof. Esiri has been supported by the Oxford Biomedical Research Centre and the National Institute of Health Research.

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Authors and Affiliations

  1. National Competence Center for Multiple Sclerosis, Department of Neurology, Haukeland University Hospital, Bergen, Norway

    Lars Bø

  2. Department of UK Clinical Medicine, University of Bergen, Bergen, Norway

    Lars Bø

  3. Neuropathology Department, West Wing, John Radcliffe Hospital, Oxford Radcliffe NHS Trust, Oxford, OX3 9DU, UK

    Margaret Esiri

  4. Department of Clinical Neurology, Oxford University, Oxford, UK

    Margaret Esiri

  5. Division of Clinical Neurology, Nottingham University Hospital, University of Nottingham, C Floor, South Block, Queen’s Medical Centre, Nottingham, NG7 2UH, UK

    Nikos Evangelou

  6. Institute of Neuropathology, University Hospital Münster, Domagkstr. 19, 48149, Münster, Germany

    Tanja Kuhlmann

Authors
  1. Lars Bø
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  2. Margaret Esiri
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  3. Nikos Evangelou
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  4. Tanja Kuhlmann
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Corresponding author

Correspondence to Nikos Evangelou .

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Editors and Affiliations

  1. School Veterinary Medicine, Dept. Medical Sciences, University of Wisconsin Madison, Linden Drive West 2015, Madison, 53706-1102, Wisconsin, USA

    Ian D. Duncan

  2. Wellcome Trust and MRC Cambridge Stem Ce, and Department of Veterinary Medicine, University Cambridge, Madingley Road, Cambridge, CB3 0ES, United Kingdom

    Robin J M Franklin

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Bø, L., Esiri, M., Evangelou, N., Kuhlmann, T. (2013). Demyelination and Remyelination in Multiple Sclerosis. In: Duncan, I., Franklin, R. (eds) Myelin Repair and Neuroprotection in Multiple Sclerosis. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-2218-1_2

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