Advertisement

Remyelination-Promoting Human IgMs: Developing a Therapeutic Reagent for Demyelinating Disease

  • A. E. Warrington
  • M. Rodriguez
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 318)

Promoting remyelination following injury to the central nervous system (CNS) promises to be an effective neuroprotective strategy to limit the loss of surviving axons and prevent disability. Studies confirm that multiple sclerosis (MS) and spinal cord injury lesions contain myelinating cells and their progenitors. Recruiting these endogenous cells to remyelinate may be of therapeutic value. This review addresses the use of antibodies reactive to CNS antigens to promote remyelination. Antibody-induced remyelination in a virus-mediated model of chronic spinal cord injury was initially observed in response to treatment with CNS reactive antisera. Monoclonal mouse and human IgMs, which bind to the surface of oligodendrocytes and myelin, were later identified that were functionally equivalent to antisera. A recombinant form of a human remyelination-promoting IgM (rHIgM22) targets areas of CNS injury and promotes maximal remyelination within 5 weeks after a single low dose (25 μg/kg). The IgM isoform of this reparative antibody is required for in vivo function. We hypothesize that the IgM clusters membrane domains and associated signaling molecules on the surface of target cells. Current therapies for MS are designed to modulate inflammation. In contrast, remyelination promoting IgMs are the first potential therapeutic molecules designed to induce tissue repair by acting within the CNS at sites of damage on the cells responsible for myelin synthesis.

Keywords

Multiple Sclerosis Spinal Cord Injury Experimental Autoimmune Encephalomyelitis Multiple Sclerosis Lesion Therapeutic Plasma Exchange 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Aarum J, Sandberg K, Haeberlein SL, Persson MA (2003) Migration and differentiation of neural precursor cells can be directed by microglia. Proc Natl Acad Sci USA 100:15983–15988PubMedCrossRefGoogle Scholar
  2. 2.
    Akiyama Y, Radtke C, Honmou O, Kocsis JD (2002) Remyelination of the spinal cord following intravenous delivery of bone marrow cells. Glia 39:229–236PubMedCrossRefGoogle Scholar
  3. 3.
    Akiyama Y, Radtke C, Kocsis JD (2002) Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells. J Neurosci 22:6623–6630PubMedGoogle Scholar
  4. 4.
    Almazan G, Honegger P, Matthieu JM (1985) Triiodothyronine stimulation of oligodendroglial differentiation and myelination. A developmental study. Dev Neurosci 7:45–54PubMedCrossRefGoogle Scholar
  5. 5.
    Annunziata P, Pluchino S, Martino T, Guazzi G (1997) High levels of cerebrospinal fluid IgM binding to myelin basic protein are associated with early benign course in multiple sclerosis. J Neuroimmunol 77:128–133PubMedCrossRefGoogle Scholar
  6. 6.
    Armstrong RC, Dorn HH, Kufta CV, Friedman E, Dubois-Dalcq ME (1992) Pre-oligodendrocytes from adult human CNS. J Neurosci 12:1538–1547PubMedGoogle Scholar
  7. 7.
    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 Remyelination-Promoting Human IgMs 231PubMedCrossRefGoogle Scholar
  8. 8.
    Asakura K, Miller DJ, Murray K, Bansal R, Pfeiffer SE, Rodriguez M (1996) Monoclonal autoantibody SCH94.03, which promotes central nervous system remyelination, recognizes an antigen on the surface of oligodendrocytes. J Neurosci Res 43:273–281PubMedCrossRefGoogle Scholar
  9. 9.
    Asakura K, Miller DJ, Pease LR, Rodriguez M (1998) Targeting of IgM kappa antibodies to oligodendrocytes promotes CNS remyelination. J Neurosci 18:7700–7708PubMedGoogle Scholar
  10. 10.
    Bansal R (2002) Fibroblast growth factors and their receptors in oligodendrocyte development: implications for demyelination and remyelination. Dev Neurosci 24:35–46PubMedCrossRefGoogle Scholar
  11. 11.
    Bansal R, Winkler S, Bheddah S (1999) Negative regulation of oligodendrocyte differentiation by galactosphingolipids. J Neurosci 19:7913–7924PubMedGoogle Scholar
  12. 12.
    Barouch R, Schwartz M (2002) Autoreactive T cells induce neurotrophin production by immune and neural cells in injured rat optic nerve: implications for protective autoimmunity. FASEB J 16:1304–1306PubMedGoogle Scholar
  13. 13.
    Barres BA, Lazar MA, Raff MC (1994) A novel role for thyroid hormone, glucocorticoids and retinoic acid in timing oligodendrocyte development. Development 120:1097–1108PubMedGoogle Scholar
  14. 14.
    Barres BA, Schmid R, Sendnter M, Raff MC (1993) Multiple extracellular signals are required for long-term oligodendrocyte survival. Development 118:283–295PubMedGoogle Scholar
  15. 15.
    Ben-Hur T, Einstein O, Mizrachi-Kol R, Ben-Menachem O, Reinhartz E, Karussis D, Abramsky O (2003) Transplanted multipotential neural precursor cells migrate into the inflamed white matter in response to experimental autoimmune encephalomyelitis. Glia 41:73–80PubMedCrossRefGoogle Scholar
  16. 16.
    Bieber AJ, Kerr S, Rodriguez M (2003) Efficient central nervous system remyelination requires T cells. Ann Neurol 53:680–684PubMedCrossRefGoogle Scholar
  17. 17.
    Bieber AJ, Ure DR, Rodriguez M (2005) Genetically dominant spinal cord repair in a murine model of chronic progressive multiple sclerosis. J Neuropathol Exp Neurol 64:46–57PubMedGoogle Scholar
  18. 18.
    Bieber AJ, Warrington A, Asakura K, Ciric B, Kaveri SV, Pease LR, Rodriguez M (2002) Human antibodies accelerate the rate of remyelination following lysolecithin-induced demyelination in mice. Glia 37:241–249PubMedCrossRefGoogle Scholar
  19. 19.
    Bieber AJ, Warrington A, Pease LR, Rodriguez M (2001) Humoral autoimmunity as a mediator of CNS repair. Trends Neurosci 24:S39–S44PubMedCrossRefGoogle Scholar
  20. 20.
    Bjartmar C, Trapp BD (2001) Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences. Curr Opin Neurol 14:271–278PubMedCrossRefGoogle Scholar
  21. 21.
    Blakemore WF (1973) Demyelination of the superior cerebellar peduncle in the mouse induced by cuprizone. J Neurol Sci 20:63–72PubMedCrossRefGoogle Scholar
  22. 22.
    Blakemore WF, Crang AJ (1988) Extensive oligodendrocyte remyelination following injection of cultured central nervous system cells into demyelinating lesions in adult central nervous system. Dev Neurosci 10:1–11PubMedCrossRefGoogle Scholar
  23. 23.
    Bogler O, Wren D, Barnett SC, Land H, Noble M (1990) Cooperation between two growth factors promotes extended self-renewal and inhibits differentiation of oligodendrocyte-type- 2 astrocyte (O-2A) progenitor cells. Proc Natl Acad Sci U S A 87:6368–6372PubMedCrossRefGoogle Scholar
  24. 24.
    Bregman BS, Kunkel-Bagden E, Schnell L, Dai HN, Gao D, Schwab ME (1995) Recovery from spinal cord injury mediated by antibodies to neurite growth inhibitors. Nature 378:498–501PubMedCrossRefGoogle Scholar
  25. 25.
    Brenner T, Arnon R, Sela M, Abramsky O, Meiner Z, Riven-Kreitman R, Tarcik N, Teitelbaum D (2001) Humoral and cellular immune responses to Copolymer 1 in multiple sclerosis patients treated with Copaxone. J Neuroimmunol 115:152–160PubMedCrossRefGoogle Scholar
  26. 26.
    Bruck W, Kuhlmann T, Stadelmann C (2003) Remyelination in multiple sclerosis. J Neurol Sci 206:181–185PubMedCrossRefGoogle Scholar
  27. 27.
    Brustle O, Jones KN, Learish RD, Karram K, Choudhary K, Wiestler OD, Duncan ID, McKay RD (1999) Embryonic stem cell-derived glial precursors: a source of myelinating transplants. Science 285:754–756PubMedCrossRefGoogle Scholar
  28. 28.
    Caroni P, Schwab ME (1988) Antibody against myelin-associated inhibitor of neurite growth neutralizes nonpermissive substrate properties of CNS white matter. Neuron 1:85–96PubMedCrossRefGoogle Scholar
  29. 29.
    . Chang A, Nishiyama A, Peterson J, Prineas J, Trapp BD (2000) NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions. J Neurosci 20:6404–6412 232 A.E. Warrington, M. RodriguezGoogle Scholar
  30. 30.
    Chang A, Tourtellotte WW, Rudick R, Trapp BD (2002) Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N Engl J Med 346:165–173PubMedCrossRefGoogle Scholar
  31. 31.
    Chen MS, Huber AB, van der Haar ME, Frank M, Schnell L, Spillmann AA, Christ F, Schwab ME (2000) Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1. Nature 403:434–439PubMedCrossRefGoogle Scholar
  32. 32.
    Ciric B, Howe CL, Paz Soldan M, Warrington AE, Bieber AJ, Van Keulen V, Rodriguez M, Pease LR (2003) Human monoclonal IgM antibody promotes CNS myelin repair independent of Fc function. Brain Pathol 13:608–616PubMedGoogle Scholar
  33. 33.
    Ciric B, VanKeulen V, Rodriguez M, Kyle RA, Gertz MA, Pease LR (2001) Clonal evolution in Waldenstrom macroglobulinemia highlights functional role of B-cell receptor. Blood 97:321–323PubMedCrossRefGoogle Scholar
  34. 34.
    Cohen IR, Schwartz M (1999) Autoimmune maintenance and neuroprotection of the central nervous system. J Neuroimmunol 100:111–114PubMedCrossRefGoogle Scholar
  35. 35.
    Dal Canto MC, Lipton HL (1977) Multiple sclerosis. Animal model: Theiler’s virus infection in mice. Am J Pathol 88:497–500PubMedGoogle Scholar
  36. 36.
    Dodel R, Hampel H, Depboylu C, Lin S, Gao F, Schock S, Jackel S, Wei X, Buerger K, Hoft C, Hemmer B, Moller HJ, Farlow M, Oertel WH, Sommer N, Du Y (2002) Human antibodies against amyloid beta peptide: a potential treatment for Alzheimer’s disease. Ann Neurol 52:253–256PubMedCrossRefGoogle Scholar
  37. 37.
    Duncan ID (1996) Glial cell transplantation and remyelination of the central nervous system. Neuropathol Appl Neurobiol 22:87–100PubMedCrossRefGoogle Scholar
  38. 38.
    Dyer CA (1993) Novel oligodendrocyte transmembrane signaling systems. Investigations utilizing antibodies as ligands. Mol Neurobiol 7:1–22PubMedCrossRefGoogle Scholar
  39. 39.
    Dyer CA, Benjamins JA (1988) Redistribution and internalization of antibodies to galactocerebroside by oligodendroglia. J Neurosci 8:883–891PubMedGoogle Scholar
  40. 40.
    Einstein O, Karussis D, Grigoriadis N, Mizrachi-Kol R, Reinhartz E, Abramsky O, Ben-Hur T (2003) Intraventricular transplantation of neural precursor cell spheres attenuates acute experimental allergic encephalomyelitis. Mol Cell Neurosci 24:1074–1082PubMedCrossRefGoogle Scholar
  41. 41.
    Ellezam B, Bertrand J, Dergham P, McKerracher L (2003) Vaccination stimulates retinal ganglion cell regeneration in the adult optic nerve. Neurobiol Dis 12:1–10PubMedCrossRefGoogle Scholar
  42. 42.
    Feigin I, Popoff N (1966) Regeneration of myelin in multiple sclerosis. The role of mesenchymal cells in such regeneration and in myelin formation in the peripheral nervous system. Neurology 16:364–372PubMedGoogle Scholar
  43. 43.
    Fernandez M, Giuliani A, Pirondi S, D’Intino G, Giardino L, Aloe L, Levi-Montalcini R, Calza L (2004) Thyroid hormone administration enhances remyelination in chronic demyelinating inflammatory disease. Proc Natl Acad Sci U S A 101:16363–16368PubMedCrossRefGoogle Scholar
  44. 44.
    Franklin RJ (2002) Why does remyelination fail in multiple sclerosis? Nat Rev Neurosci 3:705–714PubMedCrossRefGoogle Scholar
  45. 45.
    Franklin RJ, Gilson JM, Blakemore WF (1997) Local recruitment of remyelinating cells in the repair of demyelination in the central nervous system. J Neurosci Res 50:337–344PubMedCrossRefGoogle Scholar
  46. 46.
    Franklin RJ, Hinks GL, Woodruff RH, O’Leary MT (2001) What roles do growth factors play in CNS remyelination? Prog Brain Res 132:185–193PubMedCrossRefGoogle Scholar
  47. 47.
    Gaiano N, Fishell G (1998) Transplantation as a tool to study progenitors within the vertebrate nervous system. J Neurobiol 36:152–161PubMedCrossRefGoogle Scholar
  48. 48.
    Goddard DR, Berry M, Butt AM (1999) In vivo actions of fibroblast growth factor-2 and insulin-like growth factor-I on oligodendrocyte development and myelination in the central nervous system. J Neurosci Res 57:74–85PubMedCrossRefGoogle Scholar
  49. 49.
    GrandPre T, Nakamura F, Vartanian T, Strittmatter SM (2000) Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature 403:439–444PubMedCrossRefGoogle Scholar
  50. 50.
    Guimond SE, Turnbull JE (1999) Fibroblast growth factor receptor signalling is dictated by specific heparan sulphate saccharides. Curr Biol 9:1343–1346PubMedCrossRefGoogle Scholar
  51. 51.
    Hall SM (1972) The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord. J Cell Sci 10:535–546PubMedGoogle Scholar
  52. 52.
    Hammarberg H, Lidman O, Lundberg C, Eltayeb SY, Gielen AW, Muhallab S, Svenningsson A, Linda H, van Der Meide PH, Cullheim S, Olsson T, Piehl F (2000) Neuroprotection by encephalomyelitis: rescue of mechanically injured neurons and neurotrophin production by CNS-infiltrating T and natural killer cells. J Neurosci 20:5283-5291PubMedGoogle Scholar
  53. 53.
    Herndon RM, Price DL, Weiner LP (1977) Regeneration of oligodendroglia during recovery from demyelinating disease. Science 195:693-694PubMedCrossRefGoogle Scholar
  54. 54.
    Hohlfeld R, Kerschensteiner M, Stadelmann C, Lassmann H, Wekerle H (2000) The neuro- protective effect of inflammation: implications for the therapy of multiple sclerosis. J Neuroimmunol 107:161-166PubMedCrossRefGoogle Scholar
  55. 55.
    Howe CL, Bieber AJ, Warrington AE, Pease LR, Rodriguez M (2004) Antiapoptotic signal- ing by a remyelination-promoting human antimyelin antibody. Neurobiol Dis 15:120-131PubMedCrossRefGoogle Scholar
  56. 56.
    Howe CL, Mayoral S, Rodriguez M (2006) Activated microglia stimulate transcriptional changes in primary oligodendrocytes via IL-1beta. Neurobiol Dis 23:731-739PubMedCrossRefGoogle Scholar
  57. 57.
    Huang DW, McKerracher L, Braun PE, David S (1999) A therapeutic vaccine approach to stimulate axon regeneration in the adult mammalian spinal cord. Neuron 24:639-647PubMedCrossRefGoogle Scholar
  58. 58.
    Hunter SF, Miller DJ, Rodriguez M (1997) Monoclonal remyelination-promoting natural autoantibody SCH 94.03: pharmacokinetics and in vivo targets within demyelinated spinal cord in a mouse model of multiple sclerosis. J Neurol Sci 150:103-113PubMedCrossRefGoogle Scholar
  59. 59.
    Imitola J, Comabella M, Chandraker AK, Dangond F, Sayegh MH, Snyder EY, Khoury SJ (2004) Neural stem/progenitor cells express costimulatory molecules that are differentially regulated by inflammatory and apoptotic stimuli. Am J Pathol 164:1615-1625PubMedGoogle Scholar
  60. 60.
    Jeffery ND, Blakemore WF (1995) Remyelination of mouse spinal cord axons demyelinated by local injection of lysolecithin. J Neurocytol 24:775-781PubMedCrossRefGoogle Scholar
  61. 61.
    Jeffery ND, Blakemore WF (1997) Locomotor deficits induced by experimental spinal cord demyelination are abolished by spontaneous remyelination. Brain 120:27-37PubMedCrossRefGoogle Scholar
  62. 62.
    Jeffery ND, Crang AJ, O’Leary M T, Hodge SJ, Blakemore WF (1999) Behavioural conse- quences of oligodendrocyte progenitor cell transplantation into experimental demyelinating lesions in the rat spinal cord. Eur J Neurosci 11:1508-1514PubMedCrossRefGoogle Scholar
  63. 63.
    Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB (1995) Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind pla- cebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology 45:1268-1276PubMedGoogle Scholar
  64. 64.
    Johnson KP, Brooks BR, Ford CC, Goodman A, Guarnaccia J, Lisak RP, Myers LW, Panitch HS, Pruitt A, Rose JW, Kachuck N, Wolinsky JS (2000) Sustained clinical benefits of glati- ramer acetate in relapsing multiple sclerosis patients observed for 6 years. Copolymer 1 Multiple Sclerosis Study Group. Mult Scler 6:255-266PubMedGoogle Scholar
  65. 65.
    Jones TB, Basso DM, Sodhi A, Pan JZ, Hart RP, MacCallum RC, Lee S, Whitacre CC, Popovich PG (2002) Pathological CNS autoimmune disease triggered by traumatic spinal cord injury: implications for autoimmune vaccine therapy. J Neurosci 22:2690-2700PubMedGoogle Scholar
  66. 66.
    Kasahara K, Watanabe K, Takeuchi K, Kaneko H, Oohira A, Yamamoto T, Sanai Y (2000) Involvement of gangliosides in glycosylphosphatidylinositol-anchored neuronal cell adhe- sion molecule TAG-1 signaling in lipid rafts. J Biol Chem 275:34701-34709PubMedCrossRefGoogle Scholar
  67. 67.
    Kasahara K, Watanabe Y, Yamamoto T, Sanai Y (1997) Association of Src family tyrosine kinase Lyn with ganglioside GD3 in rat brain. Possible regulation of Lyn by glycosphingoli- pid in caveolae-like domains. J Biol Chem 272:29947-29953PubMedCrossRefGoogle Scholar
  68. 68.
    Keegan BM, Noseworthy JH (2002) Multiple sclerosis. Annu Rev Med 53:285-302PubMedCrossRefGoogle Scholar
  69. 69.
    Keegan M, Konig F, McClelland R, Bruck W, Morales Y, Bitsch A, Panitch H, Lassmann H, Weinshenker B, Rodriguez M, Parisi J, Lucchinetti CF (2005) Relation between humoral pathologi- cal changes in multiple sclerosis and response to therapeutic plasma exchange. Lancet 366:579-582PubMedCrossRefGoogle Scholar
  70. 70.
    Keirstead HS, Blakemore WF (1999) The role of oligodendrocytes and oligodendrocyte pro- genitors in CNS remyelination. Adv Exp Med Biol 468:183-197PubMedGoogle Scholar
  71. 71.
    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 neuro- trophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflamma- tion? J Exp Med 189:865-870PubMedCrossRefGoogle Scholar
  72. 72.
    Khalili K, White MK, Lublin F, Ferrante P, Berger JR (2007) Reactivation of JC virus and development of PML in patients with multiple sclerosis. Neurology 68:985-990PubMedCrossRefGoogle Scholar
  73. 73.
    Kohama I, Lankford KL, Preiningerova J, White FA, Vollmer TL, Kocsis JD (2001) Transplantation of cryopreserved adult human Schwann cells enhances axonal conduction in demyelinated spinal cord. J Neurosci 21:944-950PubMedGoogle Scholar
  74. 74.
    Koshizuka S, Okada S, Okawa A, Koda M, Murasawa M, Hashimoto M, Kamada T, Yoshinaga K, Murakami M, Moriya H, Yamazaki M (2004) Transplanted hematopoietic stem cells from bone marrow differentiate into neural lineage cells and promote functional recovery after spinal cord injury in mice. J Neuropathol Exp Neurol 63:64-72PubMedGoogle Scholar
  75. 75.
    Kotter MR, Setzu A, Sim FJ, Van Rooijen N,Franklin RJ (2001) Macrophage depletion impairs oligodendrocyte remyelination following lysolecithin-induced demyelination. Glia 35:204-212PubMedCrossRefGoogle Scholar
  76. 76.
    Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106-2112PubMedCrossRefGoogle Scholar
  77. 77.
    Lisak RP, Zweiman B, Blanchard N, Rorke LB (1983) Effect of treatment with Copolymer 1 (Cop-1) on the in vivo and in vitro manifestations of experimental allergic encephalomy- elitis (EAE). J Neurol Sci 62:281-293PubMedCrossRefGoogle Scholar
  78. 78.
    Liu S, Qu Y, Stewart TJ, Howard MJ, Chakrabortty S, Holekamp TF, McDonald JW (2000) Embryonic stem cells differentiate into oligodendrocytes and myelinate in culture and after spinal cord transplantation. Proc Natl Acad Sci U S A 97:6126-6131PubMedCrossRefGoogle Scholar
  79. 79.
    Lucchinetti C, Bruck W (2004) The pathology of primary progressive multiple sclerosis. Mult Scler 10 [Suppl 1]:S23-S30PubMedCrossRefGoogle Scholar
  80. 80.
    Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H (1999) A quan- titative analysis of oligodendrocytes in multiple sclerosis lesions. A study of 113 cases. Brain 122:2279-2295PubMedCrossRefGoogle Scholar
  81. 81.
    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 47:707-717PubMedCrossRefGoogle Scholar
  82. 82.
    Lucchinetti CF, Brueck W, Rodriguez M, Lassmann H (1998) Multiple sclerosis: lessons from neuropathology. Semin Neurol 18:337-349PubMedCrossRefGoogle Scholar
  83. 83.
    Marta CB, Montano MB, Taylor CM, Taylor AL, Bansal R, Pfeiffer SE (2005) Signaling cascades activated upon antibody cross-linking of myelin oligodendrocyte glycoprotein: potential implications for multiple sclerosis. J Biol Chem 280:8985-8993PubMedCrossRefGoogle Scholar
  84. 84.
    Marta CB, Taylor CM, Coetzee T, Kim T, Winkler S, Bansal R, Pfeiffer SE (2003) Antibody cross-linking of myelin oligodendrocyte glycoprotein leads to its rapid repartitioning into detergent-insoluble fractions, and altered protein phosphorylation and cell morphology. J Neurosci 23:5461-5471PubMedGoogle Scholar
  85. 85.
    Mason JL, Toews A, Hostettler JD, Morell P, Suzuki K, Goldman JE, Matsushima GK (2004) Oligodendrocytes and progenitors become progressively depleted within chronically demyelinated lesions. Am J Pathol 164:1673-1682PubMedGoogle Scholar
  86. 86.
    Matthews AE, Weiss SR, Paterson Y (2002) Murine hepatitis virus - a model for virus- induced CNS demyelination. J Neurovirol 8:76-85PubMedCrossRefGoogle Scholar
  87. 87.
    Mayer M, Bhakoo K, Noble M (1994) Ciliary neurotrophic factor and leukemia inhibitory factor promote the generation, maturation and survival of oligodendrocytes in vitro. Development 120:143-153PubMedGoogle Scholar
  88. 88.
    McDonald JW, Liu XZ, Qu Y, Liu S, Mickey SK, Turetsky D, Gottlieb DI, Choi DW (1999) Transplanted embryonic stem cells survive, differentiate and promote recovery in injured rat spinal cord. Nat Med 5:1410-1412PubMedCrossRefGoogle Scholar
  89. 89.
    McGavern DB, Murray PD, Rivera-Quinones C, Schmelzer JD, Low PA, Rodriguez M (2000) Axonal loss results in spinal cord atrophy, electrophysiological abnormalities and neurological deficits following demyelination in a chronic inflammatory model of multiple sclerosis. Brain 123:519-531PubMedCrossRefGoogle Scholar
  90. 90.
    McMorris FA, Dubois-Dalcq M (1988) Insulin-like growth factor I promotes cell prolifera- tion and oligodendroglial commitment in rat glial progenitor cells developing in vitro. J Neurosci Res 21:199-209PubMedCrossRefGoogle Scholar
  91. 91.
    McMorris FA, Mozell RL, Carson MJ, Shinar Y, Meyer RD, Marchetti N (1993) Regulation of oligodendrocyte development and central nervous system myelination by insulin-like growth factors. Ann N Y Acad Sci 692:321-334PubMedCrossRefGoogle Scholar
  92. 92.
    McTigue DM, Horner PJ, Stokes BT, Gage FH (1998) Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord. J Neurosci 18:5354-5365PubMedGoogle Scholar
  93. 93.
    Mews I, Bergmann M, Bunkowski S, Gullotta F, Bruck W (1998) Oligodendrocyte and axon pathology in clinically silent multiple sclerosis lesions. Mult Scler 4:55-62PubMedGoogle Scholar
  94. 94.
    Mezey E, Chandross KJ, Harta G, Maki RA, McKercher SR (2000) Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow. Science 290:1779-1782PubMedCrossRefGoogle Scholar
  95. 95.
    Mikami Y, Okano H, Sakaguchi M, Nakamura M, Shimazaki T, Okano HJ, Kawakami Y, Toyama Y, Toda M (2004) Implantation of dendritic cells in injured adult spinal cord results in activation of endogenous neural stem/progenitor cells leading to de novo neurogenesis and functional recovery. J Neurosci Res 76:453-465PubMedCrossRefGoogle Scholar
  96. 96.
    Miller DH, Khan OA, Sheremata WA, Blumhardt LD, Rice GP, Libonati MA, Willmer- Hulme AJ, Dalton CM, Miszkiel KA, O’Connor PW (2003) A controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 348:15-23PubMedCrossRefGoogle Scholar
  97. 97.
    Miller DJ, Sanborn KS, Katzmann JA, Rodriguez M (1994) Monoclonal autoantibodies pro- mote central nervous system repair in an animal model of multiple sclerosis. J Neurosci 14:6230-6238PubMedGoogle Scholar
  98. 98.
    Mitsunaga Y, Ciric B, Van Keulen V, Warrington AE, Paz Soldan M, Bieber AJ, Rodriguez M, Pease LR (2002) Direct evidence that a human antibody derived from patient serum can promote myelin repair in a mouse model of chronic-progressive demyelinating disease. FASEB J 16:1325-1327PubMedGoogle Scholar
  99. 99.
    Moalem G, Monsonego A, Shani Y, Cohen IR, Schwartz M (1999) Differential T cell response in central and peripheral nerve injury: connection with immune privilege. FASEB J 13:1207-1217PubMedGoogle Scholar
  100. 100.
    Muir DA, Compston DA (1996) Growth factor stimulation triggers apoptotic cell death in mature oligodendrocytes. J Neurosci Res 44:1-11PubMedCrossRefGoogle Scholar
  101. 101.
    Murray PD, Pavelko KD, Leibowitz J, Lin X, Rodriguez M (1998) CD4(+) and CD8(+) T cells make discrete contributions to demyelination and neurologic disease in a viral model of multiple sclerosis. J Virol 72:7320-7329PubMedGoogle Scholar
  102. 102.
    Nait-Oumesmar B, Decker L, Lachapelle F, Avellana-Adalid V, Bachelin C, Van Evercooren AB (1999) Progenitor cells of the adult mouse subventricular zone proliferate, migrate and differentiate into oligodendrocytes after demyelination. Eur J Neurosci 11:4357-4366PubMedCrossRefGoogle Scholar
  103. 103.
    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 104:4694-4699PubMedCrossRefGoogle Scholar
  104. 104.
    Njenga MK, Murray PD, McGavern D, Lin X, Drescher KM, Rodriguez M (1999) Absence of spontaneous central nervous system remyelination in class II-deficient mice infected with Theiler’s virus. J Neuropathol Exp Neurol 58:78-91PubMedCrossRefGoogle Scholar
  105. 105.
    Noble M, Murray K, Stroobant P, Waterfield MD, Riddle P (1988) Platelet-derived growth fac- tor promotes division and motility and inhibits premature differentiation of the oligodendrocyte/ type-2 astrocyte progenitor cell. Nature 333:560-562PubMedCrossRefGoogle Scholar
  106. 106.
    Noseworthy JH, Gold R, Hartung HP (1999) Treatment of multiple sclerosis: recent trials and future perspectives. Curr Opin Neurol 12:279-293PubMedCrossRefGoogle Scholar
  107. 107.
    Nunes MC, Roy NS, Keyoung HM, Goodman RR, McKhann G 2nd, Jiang L, Kang J, Nedergaard M, Goldman SA (2003) Identification and isolation of multipotential neural progenitor cells from the subcortical white matter of the adult human brain. Nat Med 9:439-447PubMedCrossRefGoogle Scholar
  108. 108.
    Pannu R, Christie DK, Barbosa E, Singh I, Singh AK (2007) Post-trauma Lipitor treatment prevents endothelial dysfunction, facilitates neuroprotection, and promotes locomotor recovery following spinal cord injury. J Neurochem 101:182-200PubMedCrossRefGoogle Scholar
  109. 109.
    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 129:3165-3172PubMedCrossRefGoogle Scholar
  110. 110.
    Pavelko KD, van Engelen BG, Rodriguez M (1998) Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination. J Neurosci 18:2498-2505PubMedGoogle Scholar
  111. 111.
    Paz Soldan MM, Warrington AE, Bieber AJ, Ciric B, Van Keulen V, Pease LR, Rodriguez M (2003) Remyelination-promoting antibodies activate distinct Ca2+ influx pathways in astrocytes and oligodendrocytes: relationship to the mechanism of myelin repair. Mol Cell Neurosci 22:14-24PubMedCrossRefGoogle Scholar
  112. 112.
    Penderis J, Shields SA, Franklin RJ (2003) Impaired remyelination and depletion of oligodendrocyte progenitors does not occur following repeated episodes of focal demyelination in the rat central nervous system. Brain 126:1382-1391PubMedCrossRefGoogle Scholar
  113. 113.
    Perier O, Gregoire A (1965) Electron microscopic features of multiple sclerosis lesions. Brain 88:937-952PubMedCrossRefGoogle Scholar
  114. 114.
    Pirko I, Ciric B, Gamez J, Bieber AJ, Warrington AE, Johnson AJ, Hanson DP, Pease LR, Macura SI, Rodriguez M (2004) A human antibody that promotes remyelination enters the CNS and decreases lesion load as detected by T2-weighted spinal cord MRI in a virusinduced murine model of MS. FASEB J 18:1577-1579PubMedGoogle Scholar
  115. 115.
    Pluchino S, Quattrini A, Brambilla E, Gritti A, Salani G, Dina G, Galli R, Del Carro U, Amadio S, Bergami A, Furlan R, Comi G, Vescovi AL, Martino G (2003) Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 422:688-694PubMedCrossRefGoogle Scholar
  116. 116.
    Prabhakar S, D’Souza S, Antel JP, McLaurin J, Schipper HM, Wang E (1995) Phenotypic and cell cycle properties of human oligodendrocytes in vitro. Brain Res 672:159-169PubMedCrossRefGoogle Scholar
  117. 117.
    Prineas JW, Barnard RO, Kwon EE, Sharer LR, Cho ES (1993) Multiple sclerosis: remyelination of nascent lesions. Ann Neurol 33:137-151PubMedCrossRefGoogle Scholar
  118. 118.
    Prineas JW, Wright RG (1978) Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. Lab Invest 38:409-421PubMedGoogle Scholar
  119. 119.
    Qian X, Davis AA, Goderie SK, Temple S (1997) FGF2 concentration regulates the generation of neurons and glia from multipotent cortical stem cells. Neuron 18:81-93PubMedCrossRefGoogle Scholar
  120. 120.
    Raine CS, Stone SH (1977) Animal model for multiple sclerosis. Chronic experimental allergic encephalomyelitis in inbred guinea pigs. N Y State J Med 77:1693-1696PubMedGoogle Scholar
  121. 121.
    Rapalino O, Lazarov-Spiegler O, Agranov E, Velan GJ, Yoles E, Fraidakis M, Solomon A, Gepstein R, Katz A, Belkin M, Hadani M, Schwartz M (1998) Implantation of stimulated homologous macrophages results in partial recovery of paraplegic rats. Nat Med 4:814-821PubMedCrossRefGoogle Scholar
  122. 122.
    Rapraeger AC, Krufka A, Olwin BB (1991) Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation. Science 252:1705-1758PubMedCrossRefGoogle Scholar
  123. 123.
    Richardson WD, Pringle N, Mosley MJ, Westermark B, Dubois-Dalcq M (1988) A role for platelet-derived growth factor in normal gliogenesis in the central nervous system. Cell 53:309-319PubMedCrossRefGoogle Scholar
  124. 124.
    Riggott MJ, Matthew WD (1997) Neurite outgrowth is enhanced by anti-idiotypic monoclonal antibodies to the ganglioside GM1. Exp Neurol 145:278-287PubMedCrossRefGoogle Scholar
  125. 125.
    Rivera-Quinones C, McGavern D, Schmelzer JD, Hunter SF, Low PA, Rodriguez M (1998) Absence of neurological deficits following extensive demyelination in a class I-deficient murine model of multiple sclerosis. Nat Med 4:187-193PubMedCrossRefGoogle Scholar
  126. 126.
    Robinson S, Tani M, Strieter RM, Ransohoff RM, Miller RH (1998) The chemokine growthregulated oncogene-alpha promotes spinal cord oligodendrocyte precursor proliferation. J Neurosci 18:10457-10563PubMedGoogle Scholar
  127. 127.
    Rodriguez M (1991) Immunoglobulins stimulate central nervous system remyelination: electron microscopic and morphometric analysis of proliferating cells. Lab Invest 64:358-370PubMedGoogle Scholar
  128. 128.
    Rodriguez M (2003) A function of myelin is to protect axons from subsequent injury: implications for deficits in multiple sclerosis. Brain 126:751-752PubMedCrossRefGoogle Scholar
  129. 129.
    Rodriguez M (2007) Effectors of demyelination and remyelination in the CNS: Implications for multiple sclerosis. Brain Pathol 17:219-229PubMedCrossRefGoogle Scholar
  130. 130.
    Rodriguez M, Karnes WE, Bartleson JD, Pineda AA (1993) Plasmapheresis in acute episodes of fulminant CNS inflammatory demyelination. Neurology 43:1100-1104PubMedGoogle Scholar
  131. 131.
    Rodriguez M, Lennon VA (1990) Immunoglobulins promote remyelination in the central nervous system. Ann Neurol 27:12-17PubMedCrossRefGoogle Scholar
  132. 132.
    Rodriguez M, Lennon VA, Benveniste EN, Merrill JE (1987) Remyelination by oligodendrocytes stimulated by antiserum to spinal cord. J Neuropathol Exp Neurol 46:84-95PubMedCrossRefGoogle Scholar
  133. 133.
    Rodriguez M, Miller DJ, Lennon VA (1996) Immunoglobulins reactive with myelin basic protein promote CNS remyelination. Neurology 46:538-545PubMedGoogle Scholar
  134. 134.
    Rodriguez M, Oleszak E, Leibowitz J (1987) Theiler’s murine encephalomyelitis: a model of demyelination and persistence of virus. Crit Rev Immunol 7:325-365PubMedGoogle Scholar
  135. 135.
    Rodriguez M, Scheithauer BW, Forbes G, Kelly PJ (1993) Oligodendrocyte injury is an early event in lesions of multiple sclerosis. Mayo Clin Proc 68:627-636PubMedGoogle Scholar
  136. 136.
    Rubin BP, Dusart I, Schwab ME (1994) A monoclonal antibody (IN-1) which neutralizes neurite growth inhibitory proteins in the rat CNS recognizes antigens localized in CNS myelin. J Neurocytol 23:209-217PubMedCrossRefGoogle Scholar
  137. 137.
    Sasaki M, Honmou O, Akiyama Y, Uede T, Hashi K, Kocsis JD (2001) Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons. Glia 35:26-34PubMedCrossRefGoogle Scholar
  138. 138.
    Schluesener HJ, Sobel RA, Linington C, Weiner HL (1987) A monoclonal antibody against a myelin oligodendrocyte glycoprotein induces relapses and demyelination in central nervous system autoimmune disease. J Immunol 139:4016-4021PubMedGoogle Scholar
  139. 139.
    Schwab ME (1996) Structural plasticity of the adult CNS. Negative control by neurite growth inhibitory signals. Int J Dev Neurosci 14:379-385PubMedCrossRefGoogle Scholar
  140. 140.
    Schwartz M, Moalem G, Leibowitz-Amit R, Cohen IR (1999) Innate and adaptive immune responses can be beneficial for CNS repair. Trends Neurosci 22:295-299PubMedCrossRefGoogle Scholar
  141. 141.
    Setzu A, Lathia JD, Zhao C, Wells K, Rao MS, Ffrench-Constant C, Franklin RJ (2006) Inflammation stimulates myelination by transplanted oligodendrocyte precursor cells. Glia 54:297-303PubMedCrossRefGoogle Scholar
  142. 142.
    Sindic CJ, Cambiaso CL, Depre A, Laterre EC, Masson PL (1982) The concentration of IgM in the cerebrospinal fluid of neurological patients. J Neurol Sci 55:339-350PubMedCrossRefGoogle Scholar
  143. 143.
    Sindic CJ, Monteyne P, Laterre EC (1994) Occurrence of oligoclonal IgM bands in the cerebrospinal fluid of neurological patients: an immunoaffinity-mediated capillary blot study. J Neurol Sci 124:215-219PubMedCrossRefGoogle Scholar
  144. 144.
    Smith EJ, Blakemore WF, McDonald WI (1979) Central remyelination restores secure conduction. Nature 280:395-396PubMedCrossRefGoogle Scholar
  145. 145.
    Sommer I, Schachner M (1981) Monoclonal antibodies (O1 to O4) to oligodendrocyte cell surfaces: an immunocytological study in the central nervous system. Dev Biol 83:311-327PubMedCrossRefGoogle Scholar
  146. 146.
    Spirman N, Sela BA, Gitler C, Calef E, Schwartz M (1984) Regenerative capacity of the goldfish visual system is affected by antibodies specific to gangliosides injected intraocularly. J Neuroimmunol 6:197-207PubMedCrossRefGoogle Scholar
  147. 147.
    Spirman N, Sela BA, Schwartz M (1982) Antiganglioside antibodies inhibit neuritic outgrowth from regenerating goldfish retinal explants. J Neurochem 39:874-877PubMedCrossRefGoogle Scholar
  148. 148.
    Stohlman SA, Hinton DR (2001) Viral induced demyelination. Brain Pathol 11:92-106PubMedCrossRefGoogle Scholar
  149. 149.
    Suzuki K, Andrews JM, Waltz JM, Terry RD (1969) Ultrastructural studies of multiple sclerosis. Lab Invest 20:444-454PubMedGoogle Scholar
  150. 150.
    Teitelbaum D, Aharoni R, Sela M, Arnon R (1991) Cross-reactions and specificities of monoclonal antibodies against myelin basic protein and against the synthetic copolymer 1. Proc Natl Acad Sci U S A 88:9528-9532PubMedCrossRefGoogle Scholar
  151. 151.
    Totoiu MO, Nistor GI, Lane TE, Keirstead HS (2004) Remyelination, axonal sparing, and locomotor recovery following transplantation of glial-committed progenitor cells into the MHV model of multiple sclerosis. Exp Neurol 187:254-265PubMedCrossRefGoogle Scholar
  152. 152.
    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 338:278-285PubMedCrossRefGoogle Scholar
  153. 153.
    Tripathi R, McTigue DM (2007) Prominent oligodendrocyte genesis along the border of spinal contusion lesions. Glia 55:698-711PubMedCrossRefGoogle Scholar
  154. 154.
    Ure DR, Rodriguez M (2002) Polyreactive antibodies to glatiramer acetate promote myelin repair in murine model of demyelinating disease. FASEB J 16:1260-1262PubMedGoogle Scholar
  155. 155.
    Ure DR, Rodriguez M (2002) Preservation of neurologic function during inflammatory demyelination correlates with axon sparing in a mouse model of multiple sclerosis. Neuroscience 111:399-411PubMedCrossRefGoogle Scholar
  156. 156.
    Utzschneider DA, Archer DR, Kocsis JD, Waxman SG, Duncan ID (1994) Transplantation of glial cells enhances action potential conduction of amyelinated spinal cord axons in the myelin-deficient rat. Proc Natl Acad Sci U S A 91:53-57PubMedCrossRefGoogle Scholar
  157. 157.
    Vartanian T, Fischbach G, Miller R (1999) Failure of spinal cord oligodendrocyte development in mice lacking neuregulin. Proc Natl Acad Sci U S A 96:731-735PubMedCrossRefGoogle Scholar
  158. 158.
    Vieira P, Rajewsky K (1988) The half-lives of serum immunoglobulins in adult mice. Eur J Immunol 18:313-316PubMedCrossRefGoogle Scholar
  159. 159.
    Vincent A, Lily O, Palace J (1999) Pathogenic autoantibodies to neuronal proteins in neurological disorders. J Neuroimmunol 100:169-180PubMedCrossRefGoogle Scholar
  160. 160.
    Vyas AA, Patel HV, Fromholt SE, Heffer-Lauc M, Vyas KA, Dang J, Schachner M, Schnaar RL (2002) Gangliosides are functional nerve cell ligands for myelin-associated glycoprotein (MAG), an inhibitor of nerve regeneration. Proc Natl Acad Sci U S A 99:8412-8417PubMedCrossRefGoogle Scholar
  161. 161.
    Warrington AE, Asakura K, Bieber AJ, Ciric B, Van Keulen V, Kaveri SV, Kyle RA, Pease LR, Rodriguez M (2000) Human monoclonal antibodies reactive to oligodendrocytes promote remyelination in a model of multiple sclerosis. Proc Natl Acad Sci USA 97:6820-6825PubMedCrossRefGoogle Scholar
  162. 162.
    Warrington AE, Barbarese E, Pfeiffer SE (1993) Differential myelinogenic capacity of specific developmental stages of the oligodendrocyte lineage upon transplantation into hypomyelinating hosts. J Neurosci Res 34:1-13PubMedCrossRefGoogle Scholar
  163. 163.
    Warrington AE, Bieber AJ, Ciric B, Pease LR, Van Keulen V, Rodriguez M (2007) A recombinant human IgM promotes myelin repair after a single, very low dose. J Neurosci Res 85:967-976PubMedCrossRefGoogle Scholar
  164. 164.
    Warrington AE, Bieber AJ, Van Keulen V, Ciric B, Pease LR, Rodriguez M (2004) Neuronbinding human monoclonal antibodies support central nervous system neurite extension. J Neuropathol Exp Neurol 63:461-473PubMedGoogle Scholar
  165. 165.
    Warrington AE, Pfeiffer SE (1992) Proliferation and differentiation of O4+ oligodendrocytes in postnatal rat cerebellum: analysis in unfixed tissue slices using anti-glycolipid antibodies. J Neurosci Res 33:338-353PubMedCrossRefGoogle Scholar
  166. 166.
    Weibel D, Cadelli D, Schwab ME (1994) Regeneration of lesioned rat optic nerve fibers is improved after neutralization of myelin-associated neurite growth inhibitors. Brain Res 642:259-266PubMedCrossRefGoogle Scholar
  167. 167.
    Weinshenker BG, O’Brien PC, Petterson TM, Noseworthy JH, Lucchinetti CF, Dodick DW, Pineda AA, Stevens LN, Rodriguez M (1999) A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 46:878-886PubMedCrossRefGoogle Scholar
  168. 168.
    Weinshenker BG, Wingerchuk DM, Pittock SJ, Lucchinetti CF, Lennon VA (2006) NMOIgG: a specific biomarker for neuromyelitis optica. Dis Markers 22:197-206PubMedGoogle Scholar
  169. 169.
    Windrem MS, Nunes MC, Rashbaum WK, Schwartz TH, Goodman RA, McKhann G 2nd, Roy NS, Goldman SA (2004) Fetal and adult human oligodendrocyte progenitor cell isolates myelinate the congenitally dysmyelinated brain. Nat Med 10:93-97PubMedCrossRefGoogle Scholar
  170. 170.
    Wolswijk G (1997) Oligodendrocyte precursor cells in chronic multiple sclerosis lesions. Mult Scler 3:168-169PubMedCrossRefGoogle Scholar
  171. 171.
    Woodruff RH, Franklin RJ (1997) Growth factors and remyelination in the CNS. Histol Histopathol 12:459-466PubMedGoogle Scholar
  172. 172.
    Yajima K, Suzuki K (1979) Demyelination and remyelination in the rat central nervous system following ethidium bromide injection. Lab Invest 41:385-392PubMedGoogle Scholar
  173. 173.
    Yandava BD, Billinghurst LL, Snyder EY (1999) “Global” cell replacement is feasible via neural stem cell transplantation: evidence from the dysmyelinated shiverer mouse brain. Proc Natl Acad Sci U S A 96:7029-7034PubMedCrossRefGoogle Scholar
  174. 174.
    Yao DL, Liu X, Hudson LD, Webster HD (1995) Insulin-like growth factor I treatment reduces demyelination and up-regulates gene expression of myelin-related proteins in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 92:6190-194PubMedCrossRefGoogle Scholar
  175. 175.
    Yoles E, Hauben E, Palgi O, Agranov E, Gothilf A, Cohen A, Kuchroo V, Cohen IR, Weiner H, Schwartz M (2001) Protective autoimmunity is a physiological response to CNS trauma. J Neurosci 21:3740-3748PubMedGoogle Scholar
  176. 176.
    Ziemssen T, Ziemssen F (2005) The role of the humoral immune system in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Autoimmun Rev 4:460-467PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • A. E. Warrington
    • 1
  • M. Rodriguez
    1. 1.Department of NeurologyMayo Clinic College of MedicineRochesterUSA

    Personalised recommendations