Proliferation of Oligodendrocytes and Remyelination

  • S. K. Ludwin
Part of the NATO ASI Series book series (NSSA, volume 142)


The potential for recovery from central nervous system disease has generated great interest in CNS regeneration. In demyelinating diseases, remyelination has been more extensively studied than in the past in view of the possibility for enhancing healing. Similary the post-development brain has been shown to be far more plastic than was previously believed in terms of its capacity for regeneration and proliferation. Some of the evidence for oligodendrocyte proliferation and its role in remyelination will be reviewed in this paper.


Multiple Sclerosis Schwann Cell Myelin Basic Protein Demyelinating Disease Tritiated Thymidine 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    E. K. Adrian, Jr. M. G. Williams and F. C. George, Fine structure of reactive cells in injured nervous tissue labeled with H-thimidine injected before injury, J. Comp. Neurol., 180: 815–840 (1978).CrossRefGoogle Scholar
  2. 2.
    A. J. Aguayo, G. M. Bray and S. C. Perkins, Axon-Schwann cell relationships in neuropathies of mutant mice, Ann. N.Y. Acad. Sci., 317: 512–531 (1979).Google Scholar
  3. 3.
    L. S. Arenella and R. M. Herndon, Mature oligodendrocutes. Division following experimental demyelination in adult animals, Arch. Neurol., 41: 1162–1165 (1984).CrossRefGoogle Scholar
  4. 4.
    W. F. Blakemore, Observations on remyelination in the rabbit spinal cord following demyelination induced by lysolecithin, Neurophatol. Appl. Neurobiol., 4: 47–59 (1978).CrossRefGoogle Scholar
  5. 5.
    W. F. Blakemore, Limited remyelination of CNS axons by transplanted Schwann cells, Neuropathol. Appl. Neurobiol., 11: 73 (1985).Google Scholar
  6. 6.
    L. Bologa, J. C. Bisconte, R. Jourbert, P. J. Marangos, C. Derbin, F. Rioux, and N. Herschkowitz, Accelerated differentiation of oligodendrocytes in neuronal-rich embryonic mouse cultures, Brain Res., 252: 129–136 (1982).CrossRefGoogle Scholar
  7. 7.
    L. Bologa, A. Z’Gragger, E. Rossi and N. Herschkowitz, Differentiation and proliferation: two possible mechanisms for the regeneration of oligodendrocytes in culture, J. Neurol. Sci., 57: 419–434 (1982).CrossRefGoogle Scholar
  8. 8.
    D. Cassel, P. M. Wood, R. P. Bunge and L. Glaser, Mitogenicity of brain axolemma membranes and soluble factors for dorsal root ganglion Schwann cell, J. Cell. Biochem., 18: 433–445 (1982).CrossRefGoogle Scholar
  9. 9.
    M. C. Dal Canto and R. L. Barbano, Remyelination during remission in Theiler’s virus infection, Am. J. Pathol., 116: 30–45 (1984).Google Scholar
  10. 10.
    I. D. Duncan, A. J. Aguayo, R. P. Bunge and R. P. Wood, Transplantation of rat Schwann cells grown in tissue culture into the mouse spinal cord, J. Neurol. Sci., 49: 241–252 (1981).CrossRefGoogle Scholar
  11. 11.
    E. D. Friedman, G. Nilaver, M. Perlow, P. Carmel and N. Latov, Expression of myelin basic protein immunoreactivity in shiverer mice following intracerebral fetal cortical implants, Anat. Rec., 211: 64a (1985).Google Scholar
  12. 12.
    V. L. Friedrich and N. H. Sternberger, Dividing oligodendrocyte precursors do not stain for myelin basic protein, Soc. Neurosci. Abstr., 10: 81 (1984).Google Scholar
  13. 13.
    J. Fulcrand, J. Valat and A. Privat, Myelination gliosis and reactive gliosis in the developing optic nerve of the rat, Reprod. Nutrit. Develop., 22: 11–178 (1982).Google Scholar
  14. 14.
    D. Giulian et al., Peptides from regenerating C.N.S. promote specific populations of macroglia, Proc. Natl. Acad. Sci., 82: 4287 (1985).CrossRefGoogle Scholar
  15. 15.
    M. Gumperl and N. Baumann, Central nervous sistem myelination and remyelination by brain transplants, in: “Glial-neuronal Comunication in development and regeneration”, H. Althaus, W. Seifert, eds, Plenum Press, New York (1986).Google Scholar
  16. 16.
    B. M. Harrison, Remyelination in the central nervous system, in: “Multiple Sclerosis”, J. F. Hallpike, C. W. M. Adams and W. Tourtellotte, eds, Williams and Wilkins, Baltimore, 461–478 (1983).Google Scholar
  17. 17.
    B. K. Hartman, H. C. Agrawal, D. Agrawal and S. Kalmbach, Development and maturation of central nervous system myelin: Comparison of immunohistochemical localization of proteolipid protein and basic protein in myelin and oligodendrocytes, Proc. Natl. Acad. Sci. U.S.A., 9: 4217–4220 (1982).CrossRefGoogle Scholar
  18. 18.
    R. M. Herndon, D. L. Price and L. P. Weiner, Regeneration of oligodendroglia during recovery from demyelinating disease, Science, 195: 693–694 (1977).CrossRefGoogle Scholar
  19. 19.
    K. Imamoto, J. Paterson and C. P. LeBlond, Radioautographic investigation of gliogenesis in the corpus callosum of young rats. I. Sequential changes in oligodendrocytes, J. Comp. Neurol., 180: 115–128, 132-137 (1978).CrossRefGoogle Scholar
  20. 20.
    E. S. Johnson and S. K. Ludwin, The demonstration of recurrent demyelination and remyelination of axons in the central nervous system, Acta Neuropath., 53: 93–98 (1981).CrossRefGoogle Scholar
  21. 21.
    T. Kitamura, Y. Tsuchihashi and S. Fujita, Initial response of silver-impregnated “resting microglia” to stab wounding in rabbit hippocampus, Acta Neuropath., 44: 31–39 (1978).CrossRefGoogle Scholar
  22. 22.
    N. Latov, G. Nilaver, E. A. Zimmerman, W. G. Johnson, A. J. Silverman, R. Defendi and L. Cote, Fibrillary astrocytes proliferate in response to brain injury. A study combining immunoperoxidase technique glial fibrillary acidic protein and radioantography of tritiated thymidine, Develop. Biol., 2: 381–384 (1979).CrossRefGoogle Scholar
  23. 23.
    G. E. Lemke and G. P. Brockes, Glial growth factor: a mitogenic polypeptide of the brain and pituitary, Fed. Proc., 42: 2627–2629 (1983).Google Scholar
  24. 24.
    S. K. Ludwin, Central nervous system demyelination and remyelination in the mouse. An ultrastructural study of Cuprizone toxicity, Lab. Invest., 39: 597–612 (1978).Google Scholar
  25. 25.
    S. K. Ludwin, An autoradiographic study of cellular proliferation in remyelination of the central nervous system, Am. J. Path., 95: 683–690 (1979).Google Scholar
  26. 26.
    S. K. Ludwin, Chronic demyelination inhibits remyelination in the central nervous system. An analysis of contributing factors, Lab. Invest., 43: 382–387 (1980).Google Scholar
  27. 27.
    S. K. Ludwin, Pathology of demyelination and remyelination, in: “Demyelinating Disease: Basic and Clinical Electrophysiology”, S. G. Waxman and J. M. Ritchie, eds, Raven Press, New York, 123–168 (1981).Google Scholar
  28. 28.
    S. K. Ludwin, Proliferation of oligodendrocytes following trauma to the central nervous system, Nature (Lond), 308: 274 (1984a).CrossRefGoogle Scholar
  29. 29.
    S. K. Ludwin, The function of perineuronal satellite oligodendrocytes: An immunohistochemical study, Neuropath. Appl. Neurobiol., 10: 143–149 (1984b).CrossRefGoogle Scholar
  30. 30.
    S. K. Ludwin, The reaction of oligodendrocytes and astrocytes to trauma and implantation: A combined autoradiographic and immunohistochemical study, Lab. Invest., 52: 20–30 (1985).Google Scholar
  31. 31.
    S. K. Ludwin and M. Maitland, Long term remyelination fails to reconstitute normal thickness of central myelin sheaths, J. Neurol. Sci., 64: 193–198 (1984).CrossRefGoogle Scholar
  32. 32.
    S. K. Ludwin and N. H. Sternberger, An immunochemical study of myelin proteins during demyelination and remyelination, Acta Neuropathol., 63: 240–248 (1984).CrossRefGoogle Scholar
  33. 33.
    L. Manuelidis and E. E. Manuelidis, An autoradiographic study of the proliferation and differentiation of glial cells in vitro, Acta Neuropath., 18: 193–213 (1971).CrossRefGoogle Scholar
  34. 34.
    D. L. Meinecke, F. Webster, Fine structure of diving astroglia and oligodendroglia during myelin formation in the developing mouse spinal cord, J. Comp. Neurol., 222: 47–55 (1984).CrossRefGoogle Scholar
  35. 35.
    J. E. Merril, S. Kutsunai, C. Mohlstrom, F. Hofman, J. Groopman and D. W. Golde, Proliferation of astroglia and oligodendroglia in response to human T cell-derived factors, Science, 224: 1428–1430 (1984).CrossRefGoogle Scholar
  36. 36.
    S. Mori, Uptake of H thymidine by corpus callosum cells in rats following a stab wound of the brain, Brain Res., 46: 177–186 (1972).CrossRefGoogle Scholar
  37. 37.
    S. Mori and C. P. LeBlond, Electron microscopic identification of three classes of oligodendrocytes and a preliminary study of their proliferative activity in the corpus callosum of young rats, J. Comp. Neurol., 139: 1–80 (1970).CrossRefGoogle Scholar
  38. 38.
    J. A. Paterson, Postnatal development of oligodendrocytes, in: “Eleventh International Congress of Anatomy: Glial and Neuronal Cell Biology”, E. Acosta Vidrio, S. Fedoroff, eds., Alan R. Liss, New York, 83–92 (1981).Google Scholar
  39. 39.
    J. A. Paterson, Dividing and newly produced cells in the corpus callosum of adult mouse cerebrum as detected by light microscopic radioautography, Anat. Anzeig., (Jena), 153: 149–168 (1983).Google Scholar
  40. 40.
    B. Pettmann, J-P. Delaunoy, J. Courageot, G. Devilliers and M. Sensenbrenner, Rat brain cells in culture: Effects of brain extracts on the development of oligodendroglia-like cells, Develop. Biol., 75: 278–287 (1980).CrossRefGoogle Scholar
  41. 41.
    J. W. Prineas and F. Connell, Remyelination in multiple sclerosis, Ann. Neurol., 5: 22–31 (1979).CrossRefGoogle Scholar
  42. 42.
    J. W. Prineas, The neuropathology of multiple sclerosis, in: “Handbook of Clinical Neurology”, Koetsier, ed., Elsevier Science Publishers, Amsterdam, 213–257 (1985).Google Scholar
  43. 43.
    J. W. Prineas, E. E. Kwon, E. S. Cho, L. R. Sharer, Continual breakdown and regeneration of myelin in progressive multiple sclerosis plaques, Ann. N.Y. Acad. Sci., 436: 111–32 (1984).CrossRefGoogle Scholar
  44. 44.
    A. Privat, J. Valat and J. Fulcrand, Proliferation of neuroglial cell lines in the degenerating optic nerve of young rats. A radioautographic study, J. Neuropath. Exper. Neurol., 40: 46–60 (1981a).Google Scholar
  45. 45.
    A. Privat, J. Valat, F. Lachapelle, N. Baumann and J. Fulcrand, Radioautographic evidence for the protracted proliferation of glial cells in the central nervous system of jimpy mice, Brain Res., 248: 19–31 (1981b).Google Scholar
  46. 46.
    M. C. Raff, R. H. Miller, and M. Noble, A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium, Nature (Lond)., 303: 390–396 (1983).CrossRefGoogle Scholar
  47. 47.
    M. C. Raff, E. R. Abney, J. Sok-Scang, Reconstitution of a developmental clock in vitro: a critical role for astrocytes in the timing of oligodendrocyte differentiation, Cell, 42: 61–69 (1985).CrossRefGoogle Scholar
  48. 48.
    C. S. Raine and U. Traugott, Remyelination in chronic relapsing experimental allergic encephalomyelitis and multiple sclerosis, in: “The Pathology of the Myelinated Axon”, M. Adachi, A. Hiron, S. M. Aronson, eds., Igaki-Shoin, Tokyo, 229–275 (1985).Google Scholar
  49. 49.
    C. S. Raine, L. Scheinberg and J. M. Waltz, Multiple Sclerosis. Oligodendrocyte survival and proliferation in an active established lesion, Lab. Invest., 45: 534–546 (1981).Google Scholar
  50. 50.
    M. Sensenbrenner, J-P. Delaunoy, G. Labourdette and B. Pettmann, Effects of brain extracts on the proliferation and the maturation of astroglial and oligodendroglial cells in culture, Biochem. Soc. Transact., 10: 424–426 (1982).Google Scholar
  51. 51.
    D. L. Simpson, R. Morrison, J. De Vellis and H. R. Herschwan, Epidermal growth factor binding and mitogenic activity on purified populations of cells from the central nervous system, J. Neurosci. Res., 8: 453–462 (1982).CrossRefGoogle Scholar
  52. 52.
    R. P. Skoff, Increased proliferation of oligodendrocytes in the hypomyelinated mouse mutant-jimpy, Brain Res., 248: 19–31 (1982).CrossRefGoogle Scholar
  53. 53.
    R. P. Skoff, D. L. Price and A. Stocks, Electron microscopic autoradiographic studies of gliogenesis in rat optic nerve. I. Cell Proliferation, J. Comp. Neurol., 169: 291–312 (1976).CrossRefGoogle Scholar
  54. 54.
    N. H. Sternberger, Y. Itoyama, M. W. Kies and H. deF. Webster, Myelin basic protein demonstrated immunocytochemically in oligodendroglia prior to myelin sheath formation, Proc. Nat. Acad. Sci. USA, 75: 2521–2524 (1978b).CrossRefGoogle Scholar
  55. 55.
    N. H. Sternberger, R. H. Quarles, Y. Itoyama and H. deF. Webster, Myelin-associated glycoprotein demonstrated immunocytochemically in myelin and myelin-forming cells of developing rat, Proc. Nat. Acad. Sci., 76: 1510–1514 (1979).CrossRefGoogle Scholar
  56. 56.
    R. R. Sturrock and D. A. Mcrae, Mitotic division of oligodendrocytes which have begun myelination, J. Anat., 131: 577–582 (1980).Google Scholar
  57. 57.
    R. R. Sturrock, Electron microscopic evidence for mitotic division of oligodendrocytes, J. Anat., 132: 429–432 (1981).Google Scholar
  58. 58.
    I. Tennekoon, Y. Kishimoto, I. Singh, G. Nonaka, J-M. Bourre, The differentiation of oligodendrocytes in the rat optic nerve, Develop. Biol., 79: 149–158 (1980).CrossRefGoogle Scholar
  59. 59.
    P. Willis, M. Berry, A. C. Richres, Effects of trauma on cell production in the subependymal layer of the rat neocortex, Neuropath. Appl. Neurobiol., 2: 377–388 (1976).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • S. K. Ludwin
    • 1
  1. 1.Department of Pathology (Neuropathology)Queen’s University and Kingston General HospitalKingstonCanada

Personalised recommendations