Remyelination of the Central Nervous System

  • Charlotte C. Bruce
  • Robin J. M. Franklin
  • João B. Relvas

Myelination in the central nervous system (CNS) is carried out by oligodendrocytes. These cells produce myelin, a lipid-rich biological membrane, which forms multilamellar, spirally wrapped sheets around axons. Myelination allows rapid saltatory conduction of action potentials, and contributes to the maintenance of axonal integrity. The devastating neurological effects caused by demyelinating CNS diseases illustrate the importance of the process.


Multiple Sclerosis Multiple Sclerosis Lesion Oligodendrocyte Precursor Cell Adult Central Nervous System Oligodendrocyte Progenitor 
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.


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12. References

  1. Armstrong, R.C., Kim, J.G. and Hudson, L.D., 1995, Expression of myelin transcription factor I (MyTI), a “zinc-finger” DNA-binding protein, in developing oligodendrocytes. Glia 14: 303.PubMedGoogle Scholar
  2. Armstrong, R.C., Le, T.Q., Frost, E.E., Borke, R.C. and Vana, A.C., 2002, Absence of fibroblast growth factor 2 promotes oligodendroglial repopulation of demyelinated white matter. J. Neurosci. 22: 8574.PubMedGoogle Scholar
  3. Arnett, H.A., Wang, Y., Matsushima, G.K., Suzuki, K. and Ting, J.P., 2003, Functional genomic analysis of remyelination reveals importance of inflammation in oligodendrocyte regeneration. J. Neurosci. 23: 9824.PubMedGoogle Scholar
  4. Arnett, H.A., Fancy, S.P., Alberta, J.A., Zhao, C., Plant, S.R., Kaing, S., Raine, C.S., Rowitch, D.H., Franklin, R.J.M. and Stiles, C.D., 2004, bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS. Science 306: 2111.PubMedGoogle Scholar
  5. Awatramani, R., Scherer, S., Grinspan, J., Collarini, E., Skoff, R., O’Hagan, D., Garbern, J. and Kamholz, J., 1997, Evidence that the homeodomain protein Gtx is involved in the regulation of oligodendrocyte myelination. J. Neurosci. 17: 6657.PubMedGoogle Scholar
  6. Bansal, R. and Pfeiffer, S.E., 1997, Regulation of oligodendrocyte differentiation by fibroblast growth factors. Adv. Exp. Med. Biol. 429: 69.PubMedGoogle Scholar
  7. Baron, W., Decker, L., Colognato, H. and Ffrench-Constant, C., 2003, Regulation of integrin growth factor interactions in oligodendrocytes by lipid raft microdomains. Curr. Biol. 13: 151.PubMedGoogle Scholar
  8. Barres, B.A. and Raff, M.C., 1999, Axonal control of oligodendrocyte development. J. Cell. Biol. 147: 1123.PubMedGoogle Scholar
  9. Black, J.A., Waxman, S.G. and Smith, K.J., 2006, Remyelination of dorsal column axons by endogenous Schwann cells restores the normal pattern of Nav1.6 and Kv1.2 at nodes of Ranvier. Brain 129: 1319.PubMedGoogle Scholar
  10. Blaschuk, K.L., Frost, E.E. and Ffrench-Constant, C., 2000, The regulation of proliferation and differentiation in oligodendrocyte progenitor cells by alphaV integrins. Development 127: 1961.PubMedGoogle Scholar
  11. Cai, J., Qi, Y., Hu, X., Tan, M., Liu, Z., Zhang, J., Li, Q., Sander, M. and Qiu, M., 2005, Generation of oligodendrocyte precursor cells from mouse dorsal spinal cord independent of Nkx6 regulation and Shh signaling. Neuron 45: 41.PubMedGoogle Scholar
  12. Cannella, B., Hoban, C.J., Gao, Y.L., Garcia-Arenas, R., Lawson, D., Marchionni, M., Gwynne, D. and Raine, C.S., 1998, The neuregulin, glial growth factor 2, diminishes autoimmune demyelination and enhances remyelination in a chronic relapsing model for multiple sclerosis. Proc. Natl. Acad. Sci. USA 95: 10100.PubMedGoogle Scholar
  13. Canoll, P.D., Musacchio, J.M., Hardy, R., Reynolds, R., Marchionni, M.A. and Salzer, J.L., 1996, GGF/neuregulin is a neuronal signal that promotes the proliferation and survival and inhibits the differentiation of oligodendrocyte progenitors. Neuron 17: 229.PubMedGoogle Scholar
  14. Carroll, W.M. and Jennings, A.R., 1994, Early recruitment of oligodendrocyte precursors in CNS demyelination. Brain 117: 563.PubMedGoogle Scholar
  15. Carson, M.J., Behringer, R.R., Brinster, R.L. and McMorris, F.A., 1993, Insulin-like growth factor I increases brain growth and central nervous system myelination in transgenic mice. Neuron 10: 729.PubMedGoogle Scholar
  16. Chang, A., Nishiyama, A., Peterson, J., Prineas, J. and Trapp, B.D., 2000, NG2-positive oligodendrocyte progenitor cells in adult human brain and multiple sclerosis lesions. J. Neurosci. 20: 6404.PubMedGoogle Scholar
  17. Chang, A., Tourtellotte, W.W., Rudick, R. and Trapp, B.D., 2002, Premyelinating oligodendrocytes in chronic lesions of multiple sclerosis. N. Engl. J. Med. 346: 165.PubMedGoogle Scholar
  18. Chari, D.M. and Blakemore, W.F., 2002, Efficient recolonisation of progenitor-depleted areas of the CNS by adult oligodendrocyte progenitor cells. Glia 37: 307.PubMedGoogle Scholar
  19. Charles, P., Reynolds, R., Seilhean, D., Rougon, G., Aigrot, M.S., Niezgoda, A., Zalc, B. and Lubetzki, C., 2002, Re-expression of PSA-NCAM by demyelinated axons: an inhibitor of remyelination in multiple sclerosis? Brain 125: 1972.PubMedGoogle Scholar
  20. Colognato, H., Baron, W., Avellana-Adalid, V., Relvas, J.B., Baron-Van Evercooren, A., Georges-Labouesse, E. and Ffrench-Constant, C., 2002, CNS integrins switch growth factor signaling to promote target-dependent survival. Nat. Cell Biol. 4: 833.PubMedGoogle Scholar
  21. Coman, I., Barbin, G., Charles, P., Zalc, B. and Lubetzki, C., 2005, Axonal signals in central nervous system myelination, demyelination and remyelination. J. Neurol. Sci. 233: 67.PubMedGoogle Scholar
  22. Compston, A., 2004, Mechanisms of axon-glial injury of the optic nerve. Eye 18: 1182.PubMedGoogle Scholar
  23. Compston, A. and Coles, A., 2002, Multiple sclerosis. Lancet 359: 1221.PubMedGoogle Scholar
  24. Confavreux, C. and Vukusic, S., 2006, Natural history of multiple sclerosis: a unifying concept. Brain 129: 606.PubMedGoogle Scholar
  25. Craner, M.J., Newcombe, J., Black, J.A., Hartle, C., Cuzner, M.L. and Waxman, S.G., 2004, Molecular changes in neurons in multiple sclerosis: altered axonal expression of Nav1.2 and Nav1.6 sodium channels and Na+/Ca2+ exchanger. Proc. Natl. Acad. Sci. USA 101: 8168.PubMedGoogle Scholar
  26. Crockett, D.P., Burshteyn, M., Garcia, C., Muggironi, M. and Casaccia-Bonnefil, P., 2005, Number of oligodendrocyte progenitors recruited to the lesioned spinal cord is modulated by the levels of the cell cycle regulatory protein p27Kip-1. Glia 49: 301.PubMedGoogle Scholar
  27. Dawson, M.R., Levine, J.M. and Reynolds, R., 2000, NG2-expressing cells in the central nervous system: are they oligodendroglial progenitors? J. Neurosci. Res. 61: 471.PubMedGoogle Scholar
  28. Dubois-Dalcq, M., Ffrench-Constant, C. and Franklin, R.J.M., 2005, Enhancing central nervous system remyelination in multiple sclerosis. Neuron 48: 9.PubMedGoogle Scholar
  29. Fancy, S.P., Zhao, C. and Franklin, R.J.M., 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.PubMedGoogle Scholar
  30. Fernandez, P.A., Tang, D.G., Cheng, L., Prochiantz, A., Mudge, A.W. and Raff, M.C., 2000, Evidence that axon-derived neuregulin promotes oligodendrocyte survival in the developing rat optic nerve. Neuron 28: 81.PubMedGoogle Scholar
  31. Fields, R.D. and Burnstock, G., 2006, Purinergic signaling in neuron-glia interactions. Nat. Rev. Neurosci. 7: 423.PubMedGoogle Scholar
  32. Fields, R.D. and Stevens, B., 2000, ATP: an extracellular signaling molecule between neurons and glia. Trends Neurosci. 23: 625.PubMedGoogle Scholar
  33. Flores, A.I., Mallon, B.S., Matsui, T., Ogawa, W., Rosenzweig, A., Okamoto, T. and Macklin, W.B., 2000, Akt-mediated survival of oligodendrocytes induced by neuregulins. J. Neurosci. 20: 7622.PubMedGoogle Scholar
  34. Foote, A.K. and Blakemore, W.F., 2005, Inflammation stimulates remyelination in areas of chronic demyelination. Brain 128: 528.PubMedGoogle Scholar
  35. Franklin, R.J.M., 2002, Why does remyelination fail in multiple sclerosis? Nat. Rev. Neurosci. 3: 705.PubMedGoogle Scholar
  36. Gensert, J.M. and Goldman, J.E., 1997, Endogenous progenitors remyelinate demyelinated axons in the adult CNS. Neuron 19: 197.PubMedGoogle Scholar
  37. Givogri, M.I., Costa, R.M., Schonmann, V., Silva, A.J., Campagnoni, A.T. and Bongarzone, E.R., 2002, Central nervous system myelination in mice with deficient expression of Notch1 receptor. J. Neurosci. Res. 67: 309.PubMedGoogle Scholar
  38. Goddard, D.R., Berry, M. and Butt, A.M., 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.PubMedGoogle Scholar
  39. Gudz, T.I., Komuro, H. and Macklin, W.B., 2006, Glutamate stimulates oligodendrocyte progenitor migration mediated via an alphav integrin/myelin proteolipid protein complex. J. Neurosci. 26: 2458.PubMedGoogle Scholar
  40. Gutowski, N.J., Newcombe, J. and Cuzner, M.L., 1999, Tenascin-R and C in multiple sclerosis lesions: relevance to extracellular matrix remodelling. Neuropathol. Appl. Neurobiol. 25: 207.PubMedGoogle Scholar
  41. Gveric, D., Cuzner, M.L. and Newcombe, J., 1999, Insulin-like growth factors and binding proteins in multiple sclerosis plaques. Neuropathol. Appl. Neurobiol. 25: 215.PubMedGoogle Scholar
  42. Hampton, D.W., Rhodes, K.E., Zhao, C., Franklin, R.J. and Fawcett, J.W., 2004, The responses of oligodendrocyte precursor cells, astrocytes and microglia to a cortical stab injury, in the brain. Neuroscience 127: 813.PubMedGoogle Scholar
  43. Hinks, G.L. and Franklin, R.J.M., 1999, Distinctive patterns of PDGF-A, FGF-2, IGF-I, and TGF-beta1 gene expression during remyelination of experimentally-induced spinal cord demyelination. Mol. Cell. Neurosci. 14: 153.PubMedGoogle Scholar
  44. Hinks, G.L. and Franklin, R.J.M., 2000, Delayed changes in growth factor gene expression during slow remyelination in the CNS of aged rats. Mol. Cell. Neurosci. 16: 542.PubMedGoogle Scholar
  45. Ishibashi, T., Dakin, K.A., Stevens, B., Lee, P.R., Kozlov, S.V., Stewart, C.L. and Fields, R.D., 2006, Astrocytes promote myelination in response to electrical impulses. Neuron 49: 823.PubMedGoogle Scholar
  46. Jiang, F., Frederick, T.J. and Wood, T.L., 2001, IGF-I synergizes with FGF-2 to stimulate oligodendrocyte progenitor entry into the cell cycle. Dev. Biol. 232: 414.PubMedGoogle Scholar
  47. John, G.R., Shankar, S.L., Shafit-Zagardo, B., Massimi, A., Lee, S.C., Raine, C.S. and Brosnan, C.F., 2002, Multiple sclerosis: re-expression of a developmental pathway that restricts oligodendrocyte maturation. Nat. Med. 8: 1115.PubMedGoogle Scholar
  48. Karadottir, R., Cavelier, P., Bergersen, L.H. and Attwell, D., 2005, NMDA receptors are expressed in oligodendrocytes and activated in ischaemia. Nature 438: 1162.PubMedGoogle Scholar
  49. Karram, K., Chatterjee, N. and Trotter, J., 2005, NG2-expressing cells in the nervous system: role of the proteoglycan in migration and glial-neuron interaction. J. Anat. 207: 735.PubMedGoogle Scholar
  50. Keirstead, H.S. and Blakemore, W.F., 1997, Identification of post-mitotic oligodendrocytes incapable of remyelination within the demyelinated adult spinal cord. J. Neuropathol. Exp. Neurol. 56: 1191.PubMedGoogle Scholar
  51. Kohama, I., Lankford, K.L., Preiningerova, J., White, F.A., Vollmer, T.L. and Kocsis, J.D., 2001, Transplantation of cryopreserved adult human Schwann cells enhances axonal conduction in demyelinated spinal cord. J. Neurosci. 21: 944.PubMedGoogle Scholar
  52. Komoly, S., Hudson, L.D., Webster, H.D. and Bondy, C.A., 1992, Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination. Proc. Natl. Acad. Sci. USA 89: 1894.PubMedGoogle Scholar
  53. Kondo, T. and Raff, M., 2000, Basic helix-loop-helix proteins and the timing of oligodendrocyte differentiation. Development 127: 2989.PubMedGoogle Scholar
  54. Kornek, B. and Lassmann, H., 2003, Neuropathology of multiple sclerosis - new concepts. Brain Res. Bull. 61: 321.Google Scholar
  55. Kornek, B., Storch, M.K., Weissert, R., Wallstroem, E., Stefferl, A., Olsson, T., Linington, C., Schmidbauer, M. and Lassmann, H., 2000, Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am. J. Pathol. 157: 267.PubMedGoogle Scholar
  56. Kotter, M.R., Li, W.W., Zhao, C. and Franklin, R.J.M., 2006, Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. J. Neurosci. 26: 328.PubMedGoogle Scholar
  57. Lassmann, H., Bruck, W., Lucchinetti, C. and Rodriguez, M., 1997, Remyelination in multiple sclerosis. Mult. Scler. 3: 133.PubMedGoogle Scholar
  58. Levine, J.M. and Reynolds, R., 1999, Activation and proliferation of endogenous oligodendrocyte precursor cells during ethidium bromide-induced demyelination. Exp. Neurol. 160: 333.PubMedGoogle Scholar
  59. Levison, S.W. and Goldman, J.E., 1993, Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain. Neuron 10: 201.PubMedGoogle Scholar
  60. Li, W.W., Setzu, A., Zhao, C. and Franklin, R.J.M., 2005, Minocycline-mediated inhibition of microglia activation impairs oligodendrocyte progenitor cell responses and remyelination in a non-immune model of demyelination. J. Neuroimmunol. 158: 58.PubMedGoogle Scholar
  61. Lucchinetti, C., Bruck, W., Parisi, J., Scheithauer, B., Rodriguez, M. and Lassmann, H., 2000, Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann. Neurol. 47: 707.PubMedGoogle Scholar
  62. Ludwin, S.K., 2006, The pathogenesis of multiple sclerosis: relating human pathology to experimental studies. J. Neuropathol. Exp. Neurol. 65: 305.PubMedGoogle Scholar
  63. Maeda, Y., Solanky, M., Menonna, J., Chapin, J., Li, W. and Dowling, P., 2001, Platelet-derived growth factor-alpha receptor-positive oligodendroglia are frequent in multiple sclerosis lesions. Ann. Neurol. 49: 776.PubMedGoogle Scholar
  64. Mallon, B.S., Shick, H.E., Kidd, G.J. and Macklin, W.B., 2002, Proteolipid promoter activity distinguishes two populations of NG2-positive cells throughout neonatal cortical development. J. Neurosci. 22: 876.PubMedGoogle Scholar
  65. Marcus, K., Schmidt, O., Schaefer, H., Hamacher, M., van Hall, A. and Meyer, H.E., 2004, Proteomics-application to the brain. Int. Rev. Neurobiol. 61: 285.PubMedGoogle Scholar
  66. Mason, J.L. and Goldman, J.E., 2002, A2B5+ and O4+ cycling progenitors in the adult forebrain white matter respond differentially to PDGF-AA, FGF-2, and IGF-1. Mol. Cell. Neurosci. 20: 30.PubMedGoogle Scholar
  67. Mason, J.L., Ye, P., Suzuki, K., D’Ercole, A.J. and Matsushima, G.K., 2000, Insulin-like growth factor-1 inhibits mature oligodendrocyte apoptosis during primary demyelination. J. Neurosci. 20: 5703.PubMedGoogle Scholar
  68. Mason, J.L., Suzuki, K., Chaplin, D.D. and Matsushima. G.K., 2001, Interleukin-1beta promotes repair of the CNS. J. Neurosci. 21: 7046.PubMedGoogle Scholar
  69. Mi, S., Lee, X., Shao, Z., Thill, G., Ji, B., Relton, J., Levesque, M., Allaire, N., Perrin, S., Sands, B., Crowell, T., Cate, R.L., McCoy, J.M. and Pepinsky, R.B., 2004, LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat. Neurosci. 7: 221.PubMedGoogle Scholar
  70. Miller, R.H., 1999, Contact with central nervous system myelin inhibits oligodendrocyte progenitor maturation. Dev. Biol. 216: 359.PubMedGoogle Scholar
  71. Morris, C.M. and Wilson, K.E., 2004, High throughput approaches in neuroscience. Int. J. Dev. Neurosci. 22: 515.PubMedGoogle Scholar
  72. Murtie, J.C., Zhou, Y.X., Le, T.Q., Vana, A.C. and Armstrong, R.C., 2005, PDGF and FGF2 pathways regulate distinct oligodendrocyte lineage responses in experimental demyelination with spontaneous remyelination. Neurobiol. Dis. 19: 171.PubMedGoogle Scholar
  73. O’Leary, M.T., Hinks, G.L., Charlton, H.M. and Franklin, R.J.M., 2002, Increasing local levels of IGF-I mRNA expression using adenoviral vectors does not alter oligodendrocyte remyelination in the CNS of aged rats. Mol. Cell. Neurosci. 19: 32.PubMedGoogle Scholar
  74. Olsen, I.M. and Ffrench-Constant, C., 2005, Dynamic regulation of integrin activation by intracellular and extracellular signals controls oligodendrocyte morphology. BMC Biol. 3: 25.PubMedGoogle Scholar
  75. Omlin, F.X., 1997, Optic disc and optic nerve of the blind cape mole-rat (Georychus capensis): a proposed model for naturally occurring reactive gliosis. Brain Res. Bull. 44: 627.PubMedGoogle Scholar
  76. Penderis, J., Shields, S.A. and Franklin, R.J.M., 2003a, 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.PubMedGoogle Scholar
  77. Penderis, J., Woodruff, R.H., Lakatos, A., Li, W.W., Dunning, M.D., Zhao, C., Marchionni, M. and Franklin, R.J.M., 2003b, Increasing local levels of neuregulin (glial growth factor-2) by direct infusion into areas of demyelination does not alter remyelination in the rat CNS. Eur. J. Neurosci. 18: 2253.PubMedGoogle Scholar
  78. 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, A.L. and Martino, G., 2003, Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis. Nature 422: 688.PubMedGoogle Scholar
  79. Prineas, J.W. and Connell, F., 1979, Remyelination in multiple sclerosis. Ann. Neurol. 5: 22.PubMedGoogle Scholar
  80. Prineas, J.W., Barnard, R.O., Kwon, E.E., Sharer, L.R. and Cho, E.S., 1993, Multiple sclerosis: remyelination of nascent lesions. Ann. Neurol. 33: 137.PubMedGoogle Scholar
  81. Raff, M.C., Miller, R.H. and Noble, M., 1983, A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature 303: 390.PubMedGoogle Scholar
  82. Raine, C.S., 1997, The Norton Lecture: a review of the oligodendrocyte in the multiple sclerosis lesion. J. Neuroimmunol. 77: 135.PubMedGoogle Scholar
  83. Raine, C.S. and Wu, E., 1993, Multiple sclerosis: remyelination in acute lesions. J. Neuropathol. Exp. Neurol. 52: 199.PubMedGoogle Scholar
  84. Redwine, J.M. and Armstrong, R.C., 1998, In vivo proliferation of oligodendrocyte progenitors expressing PDGFalphaR during early remyelination. J. Neurobiol. 37: 413.PubMedGoogle Scholar
  85. Rodriguez, M., 2003, A function of myelin is to protect axons from subsequent injury: implications for deficits in multiple sclerosis. Brain 126: 751.PubMedGoogle Scholar
  86. Salter, M.G. and Fern, R., 2005, NMDA receptors are expressed in developing oligodendrocyte processes and mediate injury. Nature 438: 1167.PubMedGoogle Scholar
  87. Scolding, N., Franklin, R., Stevens, S., Heldin, C.H., Compston, A. and Newcombe, J., 1998, Oligodendrocyte progenitors are present in the normal adult human CNS and in the lesions of multiple sclerosis. Brain 121: 2221.PubMedGoogle Scholar
  88. Setzu, A., Ffrench-Constant, C. and Franklin, R.J.M., 2004, CNS axons retain their competence for myelination throughout life. Glia 45: 307.PubMedGoogle Scholar
  89. Sim, F.J., Hinks, G.L. and Franklin, R.J.M., 2000, The re-expression of the homeodomain transcription factor Gtx during remyelination of experimentally induced demyelinating lesions in young and old rat brain. Neuroscience 100: 131.PubMedGoogle Scholar
  90. Sim, F.J., Zhao, C., Penderis, J. and Franklin, R.J.M., 2002a, The age-related decrease in CNS remyelination efficiency is attributable to an impairment of both oligodendrocyte progenitor recruitment and differentiation. J. Neurosci. 22: 2451.PubMedGoogle Scholar
  91. Sobel, R.A., Chen, M., Maeda, A. and Hinojoza, J.R., 1995, Vitronectin and integrin vitronectin receptor localization in multiple sclerosis lesions. J. Neuropathol. Exp. Neurol. 54: 202.PubMedGoogle Scholar
  92. Spassky, N., Goujet-Zalc, C., Parmantier, E., Olivier, C., Martinez, S., Ivanova, A., Ikenaka, K., Macklin, W., Cerruti, I., Zalc, B. and Thomas, J.L., 1998, Multiple restricted origin of oligodendrocytes. J. Neurosci. 18: 8331.PubMedGoogle Scholar
  93. Spassky, N., Olivier, C., Perez-Villegas, E., Goujet-Zalc, C., Martinez, S., Thomas, J. and Zalc, B., 2000, Single or multiple oligodendroglial lineages: a controversy. Glia 29: 143.PubMedGoogle Scholar
  94. Stevens, B., Porta, S., Haak, L.L., Gallo, V. and Fields, R.D., 2002, Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials. Neuron 36: 855.PubMedGoogle Scholar
  95. Stidworthy, M.F., Genoud, S., Li, W.W., Leone, D.P., Mantei, N., Suter, U. and Franklin, R.J.M., 2004, Notch1 and Jagged1 are expressed after CNS demyelination, but are not a major rate-determining factor during remyelination. Brain 127: 1928.PubMedGoogle Scholar
  96. Tait, S., Gunn-Moore, F., Collinson, J.M., Huang, J., Lubetzki, C., Pedraza, L., Sherman, D.L., Colman, D.R. and Brophy, P.J., 2000, An oligodendrocyte cell adhesion molecule at the site of assembly of the paranodal axo-glial junction. J. Cell. Biol. 150: 657.PubMedGoogle Scholar
  97. Talbott, J.F., Loy, D.N., Liu, Y., Qiu, M.S., Bunge, M.B., Rao, M.S. and Whittemore, S.R., 2005, Endogenous Nkx2.2+/Olig2+ oligodendrocyte precursor cells fail to remyelinate the demyelinated adult rat spinal cord in the absence of astrocytes. Exp. Neurol. 192: 11.PubMedGoogle Scholar
  98. Targett, M.P., Sussman, J., Scolding, N., O’Leary, M.T., Compston, D.A. and Blakemore, W.F., 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.PubMedGoogle Scholar
  99. Tauber, H., Waehneldt, T.V. and Neuhoff, V., 1980, Myelination in rabbit optic nerves is accelerated by artificial eye opening. Neurosci. Lett. 16: 235.PubMedGoogle Scholar
  100. Totoiu, M.O., Nistor, G.I., Lane, T.E. and Keirstead, H.S., 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.PubMedGoogle Scholar
  101. Trapp, B.D., Peterson, J., Ransohoff, R.M., Rudick, R., Mork, S. and Bo, L., 1998, Axonal transection in the lesions of multiple sclerosis. N. Engl. J. Med. 338: 278.PubMedGoogle Scholar
  102. Vallstedt, A., Klos, J.M. and Ericson, J., 2005, Multiple dorsoventral origins of oligodendrocyte generation in the spinal cord and hindbrain. Neuron 45: 55.PubMedGoogle Scholar
  103. Viehover, A., Miller, R.H., Park, S.K., Fischbach, G. and Vartanian, T., 2001, Neuregulin: an oligodendrocyte growth factor absent in active multiple sclerosis lesions. Dev. Neurosci. 23: 377.PubMedGoogle Scholar
  104. Wang, S., Sdrulla, A.D., diSibio, G., Bush, G., Nofziger, D., Hicks, C., Weinmaster, G. and Barres, B.A., 1998, Notch receptor activation inhibits oligodendrocyte differentiation. Neuron 21: 63.PubMedGoogle Scholar
  105. Wang, S., Sdrulla, A., Johnson, J.E., Yokota, Y. and Barres, B.A., 2001, A role for the helix-loop-helix protein Id2 in the control of oligodendrocyte development. Neuron 29: 603.PubMedGoogle Scholar
  106. Wang, K.C., Kim, J.A., Sivasankaran, R., Segal, R. and He, Z., 2002, P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp. Nature 420: 74.PubMedGoogle Scholar
  107. Waxman, S.G., 1998, Demyelinating diseases-new pathological insights, new therapeutic targets. N. Engl. J. Med. 338: 323.PubMedGoogle Scholar
  108. Wilson, H.C., Onischke, C. and Raine, C.S., 2003, Human oligodendrocyte precursor cells in vitro: phenotypic analysis and differential response to growth factors. Glia 44: 153.PubMedGoogle Scholar
  109. Wolswijk, G., 1998, Chronic stage multiple sclerosis lesions contain a relatively quiescent population of oligodendrocyte precursor cells. J. Neurosci. 18: 601.PubMedGoogle Scholar
  110. Wolswijk, G., 2000, Oligodendrocyte survival, loss and birth in lesions of chronic-stage multiple sclerosis. Brain 123: 105.PubMedGoogle Scholar
  111. Wolswijk, G. and Balesar, R., 2003, Changes in the expression and localization of the paranodal protein Caspr on axons in chronic multiple sclerosis. Brain 126: 1638.PubMedGoogle Scholar
  112. Wong, S.T., Henley, J.R., Kanning, K.C., Huang, K.H., Bothwell, M. and Poo, M.M., 2002, A p75(NTR) and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein. Nat. Neurosci. 5: 1302.PubMedGoogle Scholar
  113. Woodruff, R.H., Fruttiger, M., Richardson, W.D. and Franklin, R.J.M., 2004, Platelet-derived growth factor regulates oligodendrocyte progenitor numbers in adult CNS and their response following CNS demyelination. Mol. Cell. Neurosci. 25: 252.PubMedGoogle Scholar
  114. Wren, D., Wolswijk, G. and Noble, M., 1992, In vitro analysis of the origin and maintenance of O-2A adult progenitor cells. J. Cell. Biol. 116: 167.PubMedGoogle Scholar
  115. Ye, P., Carson, J. and D’Ercole, A.J., 1995, In vivo actions of insulin-like growth factor-I (IGF-I) on brain myelination: studies of IGF-I and IGF binding protein-1 (IGFBP-1) transgenic mice. J. Neurosci. 15: 7344.PubMedGoogle Scholar
  116. Zhang, S.C., Ge, B. and Duncan, I.D., 1999, Adult brain retains the potential to generate oligodendroglial progenitors with extensive myelination capacity. Proc. Natl. Acad. Sci. USA 96: 4089.PubMedGoogle Scholar
  117. Zhao, C., Fancy, S.P., Kotter, M.R., Li, W.W. and Franklin, R.J.M., 2005a, Mechanisms of CNS remyelination-the key to therapeutic advances. J. Neurol. Sci. 233: 87.PubMedGoogle Scholar
  118. Zhao, C., Fancy, S.P., Magy, L., Urwin, J.E. and Franklin, R.J.M., 2005b, Stem cells, progenitors and myelin repair. J. Anat. 207: 251.PubMedGoogle Scholar
  119. Zhao, C., Li, W.W. and Franklin, R.J.M., 2006, Differences in the early inflammatory responses to toxin-induced demyelination are associated with the age-related decline in CNS remyelination. Neurobiol. Aging 27: 1298.PubMedGoogle Scholar

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© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Charlotte C. Bruce
    • 1
  • Robin J. M. Franklin
    • 1
  • João B. Relvas
    • 2
  1. 1.Cambridge Centre for Brain Repair, and Neuroregeneration Laboratory, Department of Veterinary MedicineUniversity of CambridgeUK
  2. 2.Department of Biology, Swiss Federal Institute of TechnologyInstitute of Cell BiologySwitzerland

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