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The demonstration of recurrent demyelination and remyelination of axons in the central nervous system

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Summary

A model for studying recurrent demyelination and remyelination in the central nervous system was developed by means of repeated administration of Cuprizone to mice. In contrast to the demyelination seen during the first course of Cuprizone, the recurrent demyelination was markedly protracted, displayed features of a “dying-back” gliopathy, and resulted in a greatly reduce inflammatory and glial reaction. The repeat remyelination also occurred at a slower tempo, varied markedly in completeness, and was associated with a diminished regeneration of oligodendrocytes. These results demonstrated that axons of the central nervous system in this model can be recurrently remyclinated if oligodendrocytes are available, that regeneration of oligodendrocytes is dependent upon the tissue reaction to demyelination, and that remyelinated axons are not more susceptible to demyelination than normal ones.

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References

  • Allt G (1972) An ultrastructural analysis of remyelination following segmental demyelination. Acta Neuropathol (Berl) 22:333–344

    Google Scholar 

  • Ballin RHM, Thomas PK (1968) Electron microscope observations in demyelination and remyelination in experimental allergic neuritis, Part 2, Remyelination. J Neurol Sci 8:225–237

    Google Scholar 

  • Blakemore WF (1973a) Demyelination of the superior cerebellar peduncle in the mouse induced by Cuprizone. J Neurol Sci 20:63–72

    Google Scholar 

  • Blakemore WF (1973b) Remyelination of the superior cerebellar peduncle in the mouse following demyelination induced by feeding Cuprizone. J Neurol Sci 20:73–83

    Google Scholar 

  • Blakemore WF (1976) Invasion of Schwann cells into the spinal cord of the rat following local injections of lysolecithin. Neuropathol Appl Neurobiol 2:21–39

    Google Scholar 

  • Blakemore WF (1978) Observations on remyelination in the rabbit spinal cord following demyelination induced by lysolecithin. Neuropathol Appl Neurobiol 4:47–59

    Google Scholar 

  • Carlton WW (1969) Spongiform encephalopathy induced in rats and guinea pigs by Cuprizone. Exp Mol Pathol 10:274–287

    Google Scholar 

  • Collins GH (1966) An electron microscopic study of remyelination in the brainstem of thiamine deficient rats. Am J Pathol 48:259–275

    Google Scholar 

  • DalCanto MC, Lipton HL (1980) Schwann cell remyelination and recurrent demyelination in the central nervous system of mice infected with attenuated Theiler's virus. Am J Pathol 98:101–122

    Google Scholar 

  • Dyck PJ (1969) Experimental hypertrophic neuropathy. Pathogenesis of onion-bulb formations produced by repeated tourniquet applications. Arch Neurol 21:73–95

    Google Scholar 

  • Elsworth S, Howell JMcC (1973) Variation in the response of mice to Cuprizone. Res Vet Sci 14:385–387

    Google Scholar 

  • Feigin I, Popoff N (1966) Regeneration of myelin in multiple sclerosis. Neurology (Minneap) 16:364–372

    Google Scholar 

  • Feigin I, Ogata J (1971) Schwann cells and peripheral myelin within human central nervous tissues. The mesenchymal character of Schwann cells. J Neuropathol Exp Neurol 30:603–612

    Google Scholar 

  • Harrison BM (1980) Remyelination by cells introduced into a stable demyelinating lesion in the central nervous system. J Neurol Sci 46:63–81

    Google Scholar 

  • Harrison BM, McDonald WI, Ochoa J (1972) Remyelination in the Diphtheria toxin lesion. J Neurol Sci 17:293–302

    Google Scholar 

  • Hirano A, Zimmerman HM, Levine S (1969) Electron microscopic observations of peripheral myelin in a central nervous system lesion. Acta Neuropathol (Berl) 12:348–365

    Google Scholar 

  • King RH, Pollard TD, Thomas PK (1975) Aberrant remyelination in chronic relapsing experimental allergic neuritis. Neuropathol Appl Neurobiol 1:367–378

    Google Scholar 

  • Ludwin SK (1978) Central nervous system demyelination and remyelination in the mouse. An ultrastructural study of Cuprizone toxicity. Lab Invest 39:597–612

    Google Scholar 

  • Ludwin SK (1979) An autoradiographic study of cellular proliferation in remyelination of the central nervous system. Am J Pathol 95:683–696

    Google Scholar 

  • Ludwin SK (1980) Chronic demyelination inhibits remyelination in the central nervous system. An analysis of contributing factors. Lab Invest 43:382–387

    Google Scholar 

  • Ludwin SK, Johnson ES (1981) Evidence for the concept of a dying-back gliopathy in demyelinating disease. Ann Neurol (in press)

  • Mori S, Leblond CP (1970) 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 139:1–30

    Google Scholar 

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

    Google Scholar 

  • Raine CS, Wisniewski H, Prineas J (1969) An ultrastructural study of experimental demyelination and remyelination. II. Chronic experimental allergic encephalomyelitis in the peripheral nervous system. Lab Invest 21:316–327

    Google Scholar 

  • Raine CS, Snyder DH, Valsamis MP, Stone SH (1974) Chronic experimental allergic encephalomyelitis in inbred guinea pigs. An ultrastructural study. Lab Invest 31:369–380

    Google Scholar 

  • Raine CS, Traugott U, Stone SH (1978) Chronic relapsing experimental allergic encephalomyelitis. CNS plaque development in unsuppressed and suppressed animals. Acta Neuropathol (Berl) 43:43–53

    Google Scholar 

  • Schoene WC, Carpenter S, Behan PO, Geschwind N (1977) “Onion bulb” formations in the central and peripheral nervous system in association with multiple sclerosis and hypertrophic polyneuropathy. Brain 100:755–773

    Google Scholar 

  • Snyder DH, Valsamis MP, Stone SH, Raine CS (1975) Progressive demyelination and reparative phenomena in chronic experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 34:209–221

    Google Scholar 

  • Snyder DH, Stone SH, Raine CS (1977) Attempts to induce chronic experimental allergic neuritis in strain 13 and Hartley guinea pigs. J Neuropathol Exp Neurol 36:488–498

    Google Scholar 

  • Thomas PK, Lascelles RG (1967) Hyperthrophic neuropathy. Q J Med 36:223–238

    Google Scholar 

  • Weller RO (1967) An electron microscopic study of hypertrophic neuropathy of Dejerine and Sottas. J Neurol Neurosurg Psychiatry 30:111–125

    Google Scholar 

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Johnson, E.S., Ludwin, S.K. The demonstration of recurrent demyelination and remyelination of axons in the central nervous system. Acta Neuropathol 53, 93–98 (1981). https://doi.org/10.1007/BF00689988

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  • DOI: https://doi.org/10.1007/BF00689988

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