Mielinização, desmielinização e remielinização no sistema nervoso central

Graça, Dominguita Lühers

doi:10.1590/S0004-282X1988000300010

Resumos

As bainhas de mielina que envolvem axônios no SNC são feitas e mantidas por oligodendrócitos. Estas células gliais formam um número variável de segmentos de mielina (internódulos): entre 1 e 200, de modo que quando uma célula é lesada junto com ela podem ser destruídos numerosos internódulos, constituindo um processo desmielinizante. Como conseqüência da destruição da célula-bainha e internódulos relacionados há uma resposta celular rápida e abundante. Esta resposta é feita por fagócitos residentes (microglia) e hematógenos. Ambas as células fagocitam os detritos celulares e de. mielina, deixando os axônios desmielinizados. Estes axônios podem permanecer desprovidos de suas bainhas e aglutinados, podem ser separados por processos de astrócitos ou podem ser remielinizados. A ocorrência do processo de remielinização depende da intensidade e tempo de exposição ao agente desmielinizante. A remielinização, com total restabelecimento da condução, pode ser realizada por oligodendrócito ou por célula de Schwann que invade o SNC sempre que os astrócitos são destruídos.

The myelin sheaths that surround axons in the CNS are made and maintained by oligodendrocytes. These glial cells can form variable numbers of myelin segments (internodules): from 1 to 200 so that when one oligodendrocyte is destroyed with preservation of the axon, many internodules can be lost, constituting a demyelinating process. As a consequence of the destruction of myelin and sheath cells a rapid and abundant cell response takes place. The response is made up by resident (microglia) and haematogenous phagocytes which phagocytose myelin and cellular debris leaving the axons demyelinated. Demyelinated axons may either stay demyelinated and clumped together or they may be separated by astrocytic processes, yet they can be remyelinated. The occurrence of remyelination depends upon the intensity and time of exposition to the demyelinating agent. Remyelination in the CNS with complete restoration of conduction may be made by oligodendrocytes or Schwann cells which invade the CNS when astrocytes are destroyed.

Dominguita Lühers Graça

Professor Adjunto, DMV, PhD - Departamento de Patologia da Universidade Federal de Santa Maria

RESUMO

As bainhas de mielina que envolvem axônios no SNC são feitas e mantidas por oligodendrócitos. Estas células gliais formam um número variável de segmentos de mielina (internódulos): entre 1 e 200, de modo que quando uma célula é lesada junto com ela podem ser destruídos numerosos internódulos, constituindo um processo desmielinizante. Como conseqüência da destruição da célula-bainha e internódulos relacionados há uma resposta celular rápida e abundante. Esta resposta é feita por fagócitos residentes (microglia) e hematógenos. Ambas as células fagocitam os detritos celulares e de. mielina, deixando os axônios desmielinizados. Estes axônios podem permanecer desprovidos de suas bainhas e aglutinados, podem ser separados por processos de astrócitos ou podem ser remielinizados. A ocorrência do processo de remielinização depende da intensidade e tempo de exposição ao agente desmielinizante. A remielinização, com total restabelecimento da condução, pode ser realizada por oligodendrócito ou por célula de Schwann que invade o SNC sempre que os astrócitos são destruídos.

SUMMARY

The myelin sheaths that surround axons in the CNS are made and maintained by oligodendrocytes. These glial cells can form variable numbers of myelin segments (internodules): from 1 to 200 so that when one oligodendrocyte is destroyed with preservation of the axon, many internodules can be lost, constituting a demyelinating process. As a consequence of the destruction of myelin and sheath cells a rapid and abundant cell response takes place. The response is made up by resident (microglia) and haematogenous phagocytes which phagocytose myelin and cellular debris leaving the axons demyelinated. Demyelinated axons may either stay demyelinated and clumped together or they may be separated by astrocytic processes, yet they can be remyelinated. The occurrence of remyelination depends upon the intensity and time of exposition to the demyelinating agent. Remyelination in the CNS with complete restoration of conduction may be made by oligodendrocytes or Schwann cells which invade the CNS when astrocytes are destroyed.

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Departamento de Patologia, Universidade Federal de Santa Maria - 91110 Santa Maria RS -Brasil.

1. Aguayo AJ, Bray GM - Developmental disorders of myelination in mouse mutants. In Sears TA (ed): Neuronal-Glial Cell Interrelationships. Springer, Berlin, 1982, pg 57.
2. Allen IV - The pathology of multiple sclerosis: fact, fiction and hypothesis. Neuropathol Appl Neurobiol 7: 169, 1981.
3. Blakemore WF - Remyelination of the superior cerebellar peduncle in the mouse following demyelination induced by feeding cuprizone. J Neurol Sci 20: 73, 1973.
4. Blakemore WF - Pattern of demyelination in the CNS. Nature 249: 577, 1974.
5. Blakemore WF - Observations on remyelination in the rabbit spinal cord following demyelination induced by lysolecithin. Neuropathol Appl Neurobiol 4: 47, 1978.
6. Blakemore WF - Myelination, demyelination and remyelination in the central nervous system. In Philipson AF, Hall LW, Pritchard WR (eds): Scientific Foundations of Veterinary Medicine. Heineman, London, 1980, pg 61.
7. Blakemore WF - Myelination, demyelination and remyelination in the CNS. In Cavanagh JB, Smith WT (eds): Recent Advances in Neuropathology. Churchill Livingstone, Edinburgh, 1982, pg 53.
8. Blakemore WF, Crang AJ, Evans RJ - The effect of chemical injury on oligodendrocytes. In Mims CA, Cuzner ML, Kelly RE (eds): Viruses and Demyeiinating Diseases. Academic Press, London, 1983, pg 167.
9. Bunge MB, Bunge RP, Ris H - Ultrastructural study of remyelination in an experimental lesion in adult cat spinal cord. J Biophys Biochem Cytol 10: 67, 1961.
10. Bunge RP, Bunge MB - Evidence that contact with connective tissue matrix is required for normal interaction between Schwann cells and nerve fibres. J Cell Biol 78: 943, 1978.
11. Bunge RP, Bunge MB, Cochran M - Some factors influencing the proliferation and differentiation of myelin-forming cells. Neurology 28 :59, 1978.
12. Clifford-Jones RE, Landon DN, McDonald WI - Remyelination during optic nerve compression. J Neurol Sci 46: 239, 1980.
13. Clifford-Jones RE, McDonald WI, Landon DN - Chronic optic nerve compression: an experimental study. Brain 108: 241, 1985.
14. French-Constant C, Raff MC - The oligodendrocyte-type-2 astrocyte cell lineage is specialized for myelination. Nature 323: 335, 1986.
15. Fish CJ - Partial demyelination in the. spinal cord. Tese. University of Cambridge, 1984.
16. Fish CJ, Blakemore WF - A model of chronic spinal cord compression in the cat. Neuropathol Appl Neurobiol 9: 109, 1983.
17. Fleury, HJA, Sheppard RD, Bornstein MB, Raine CS - Further ultrastructural observations of virus morphogenesis and myelin pathology in JHM virus encephalomyelitis. Neuropathol Appl Neurobiol 6 :165, 1980.
18. Graça DL - Investigation into ethidium bromide induced demyelination in the central nervous system. Tese. University of Cambridge, 1986.
19. Graça DL, Blakemore WF - The formation of intracytoplasmic «scrolls» followin local injections of ethidium bromide. Neuropathol Appl Neurobiol 11: 73, 1985.
20. Graça DL, Blakemore WF - Delayed remyelination in rat spinal cord following ethidium bromide injection. Neuropathol Appl Neurobiol 12: 593, 1986.
21. Harrison BM - Remyelination in the central nervous system. In Hallpike JF, Adams CWM, Tourtellotte WW (eds): Multiple Sclerosis: Pathology, Diagnosis and Treatment. Chapman, London, 1983, pg 461.
22. Harrison BM, McDonald WI - Remyelination after transient experimental compression of the spinal cord. Ann Neurol 1: 542, 1977.
23. Hirano A, Dembitzer HM - A structural analysis of the myelin sheath in the central nervous system. J Cell Biol 34: 555, 1967.
24. Hirano A, Dembitzer HM - Morphology of normal central myelinated axons. In Waxman SG (ed): Physiology and Pathobiology of Axons. Raven, New York, 1978, pg 65.
25. Kelly WR, Blakemore WF, Jagelman S, Webb HE - Demyelination induced in mice by avirulent Semliki Forest Virus: II. An ultrastructural study of focal demyelination in the brain. Neuropathol Appl Neurobiol 8: 43, 1982.
26. Kusaka H, Hirano A, Bornstein MB, Raine CS - Fine structure of astrocyte processes during serum-induced demyelination in vitro. J Neurol Sci 69: 255, 1985.
27. Lampert PW - Autoimmune and virus-induced demyelinating diseases: a review. Am J Pathol 91 :176, 1978.
28. Lampert PW - Fine structure of the demyelinating process. In Hallpike JF, Adams CWM, Tourtellotte WW (eds): Multiple Sclerosis: Pathology, Diagnosis and Management. Chapman, London, 1983, pg 29.
29. Lampert PW, Carpenter S - Electron microscopic studies on the vascular permeability and the mechanism of demyelination in experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 24: 11, 1965.
30. Leibowitz S, Hughes RAC - Immunology of the Nervous System. Edward Arnold, London, 1983.
31. Ludwin SK - Central nervous system demyelination and remyelination in the mouse: an ultrastructural study of cuprizone toxicity. Lab Invest 39: 597, 1978.
32. Ludwin SK - Chronic demyelination inhibits remyelination in the central nervous system: an analysis of contributing factors. Lab Invest 43: 382, 1980.
33. Mirsky R, Winter J, Abney ER, Pruss RM, Gavrilovic J, Raff MC - Myelin-specific proteins and glycolipids in rat Schwann cells and oligodendrocytes in culture. J Cell Biol 84: 483, 1980.
34. McDonald WI - Remyelination in relation to clinical lesions in the central nervous system. Br Med Bull 30: 186, 1974.
35. Nagashima K - Ultrastructural study of myelinating cells and sub-pial astrocytes in developing rat spinal cord. J Neurol Sci 44 :1, 1979.
36. Peters A, Palay SL, Webster H deF - The Fine Structure of the Nervous System: the Neurons and Supporting Glia. WB Saunders, Philadelphia, 1976.
37. Powell HC, Lampert PW - Oligodendrocytes and their myelin-plasma membrane connections in JHM mouse hepatitis virus encephalomyelitis. Lab Invest 33: 440, 1975.
38. Prineas JW, Raine CS - Mechanism of myelin breakdown in multiple sclerosis. J Neuropathol Exp Neurol 38: 336, 1979.
39. Raine CS - Morphology of myelin and myelination. In Morell P (ed): Myelin. Ed 2. Plenum, New York, 1984, pg 1.
40. Raine CS, Hummelgard A, Swanson E, Bornstein MB - Multiple sclerosis: serum-induced demyelination in vitro. A light and electron microscopic study. J Neurol Sci 20: 127, 1973.
41. Toro I, Ruzsa P, Rohlich P - Ultrastructure of early phagocytic stages in sinus endothelial and Kupffer cells of the liver. Exp Cell Res 26: 601, 1962.
42. Vandevelde M, Zurbriggen A, Higgins RJ, Palmer D - Spread and distribution of viral antigen in nervous system canine distemper. Acta Neuropathol (Berlin) 67: 211, 1985.
43. Waxman SG - Conduction in normal and demyelinated axons. In Pearlman AL, Collins RC (eds): Neurological Pathophysiology. Oxford Univ Press, 1984, pg 13.
44. Weller RO - Experimental demyelinating diseases and their relevance to the study of multiple sclerosis. In Matthew WB (ed): McAlpine's Multiple Sclerosis. Churchill Livingstone, Edinburgh, 1985, pg 344.
45. Whitaker JN - Demyelinating diseases. In Pearlman AL, Collins RC (eds): Neurological Pathophysiology. Oxford Univ Press, 1984, pg 274.
46. Wisniewski H, Raine CS - An ultrastructural study of experimental demyelination and remyelination: V. Central and peripheral nervous system lesions caused by diphtheria toxin. Lab Invest 25 :73, 1971.
47. Wisniewski H, Bloom BR - Primary demyelination as a non-specific consequence of a cell-mediated immune reaction. J Exp Med 141: 346, 1975.
48. Wisniewski H, Raine CS, Kay WJ - Observations on viral demyelinating encephalomyelitis: canine distemper. Lab Invest 26: 589, 1972.

Mielinização, desmielinização e remielinização no sistema nervoso central

Myelination, demyelination and remyelination in the central nervous system

Datas de Publicação

Publicação nesta coleção
17 Jun 2011
Data do Fascículo
Set 1988

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. Aguayo AJ, Bray GM - Developmental disorders of myelination in mouse mutants. In Sears TA (ed): Neuronal-Glial Cell Interrelationships. Springer, Berlin, 1982, pg 57.

[2] 2. Allen IV - The pathology of multiple sclerosis: fact, fiction and hypothesis. Neuropathol Appl Neurobiol 7: 169, 1981.

[3] 3. Blakemore WF - Remyelination of the superior cerebellar peduncle in the mouse following demyelination induced by feeding cuprizone. J Neurol Sci 20: 73, 1973.

[4] 4. Blakemore WF - Pattern of demyelination in the CNS. Nature 249: 577, 1974.

[5] 5. Blakemore WF - Observations on remyelination in the rabbit spinal cord following demyelination induced by lysolecithin. Neuropathol Appl Neurobiol 4: 47, 1978.

[6] 6. Blakemore WF - Myelination, demyelination and remyelination in the central nervous system. In Philipson AF, Hall LW, Pritchard WR (eds): Scientific Foundations of Veterinary Medicine. Heineman, London, 1980, pg 61.

[7] 7. Blakemore WF - Myelination, demyelination and remyelination in the CNS. In Cavanagh JB, Smith WT (eds): Recent Advances in Neuropathology. Churchill Livingstone, Edinburgh, 1982, pg 53.

[8] 8. Blakemore WF, Crang AJ, Evans RJ - The effect of chemical injury on oligodendrocytes. In Mims CA, Cuzner ML, Kelly RE (eds): Viruses and Demyeiinating Diseases. Academic Press, London, 1983, pg 167.

[9] 9. Bunge MB, Bunge RP, Ris H - Ultrastructural study of remyelination in an experimental lesion in adult cat spinal cord. J Biophys Biochem Cytol 10: 67, 1961.

[10] 10. Bunge RP, Bunge MB - Evidence that contact with connective tissue matrix is required for normal interaction between Schwann cells and nerve fibres. J Cell Biol 78: 943, 1978.

[11] 11. Bunge RP, Bunge MB, Cochran M - Some factors influencing the proliferation and differentiation of myelin-forming cells. Neurology 28 :59, 1978.

[12] 12. Clifford-Jones RE, Landon DN, McDonald WI - Remyelination during optic nerve compression. J Neurol Sci 46: 239, 1980.

[13] 13. Clifford-Jones RE, McDonald WI, Landon DN - Chronic optic nerve compression: an experimental study. Brain 108: 241, 1985.

[14] 14. French-Constant C, Raff MC - The oligodendrocyte-type-2 astrocyte cell lineage is specialized for myelination. Nature 323: 335, 1986.

[15] 15. Fish CJ - Partial demyelination in the. spinal cord. Tese. University of Cambridge, 1984.

[16] 16. Fish CJ, Blakemore WF - A model of chronic spinal cord compression in the cat. Neuropathol Appl Neurobiol 9: 109, 1983.

[17] 17. Fleury, HJA, Sheppard RD, Bornstein MB, Raine CS - Further ultrastructural observations of virus morphogenesis and myelin pathology in JHM virus encephalomyelitis. Neuropathol Appl Neurobiol 6 :165, 1980.

[18] 18. Graça DL - Investigation into ethidium bromide induced demyelination in the central nervous system. Tese. University of Cambridge, 1986.

[19] 19. Graça DL, Blakemore WF - The formation of intracytoplasmic «scrolls» followin local injections of ethidium bromide. Neuropathol Appl Neurobiol 11: 73, 1985.

[20] 20. Graça DL, Blakemore WF - Delayed remyelination in rat spinal cord following ethidium bromide injection. Neuropathol Appl Neurobiol 12: 593, 1986.

[21] 21. Harrison BM - Remyelination in the central nervous system. In Hallpike JF, Adams CWM, Tourtellotte WW (eds): Multiple Sclerosis: Pathology, Diagnosis and Treatment. Chapman, London, 1983, pg 461.

[22] 22. Harrison BM, McDonald WI - Remyelination after transient experimental compression of the spinal cord. Ann Neurol 1: 542, 1977.

[23] 23. Hirano A, Dembitzer HM - A structural analysis of the myelin sheath in the central nervous system. J Cell Biol 34: 555, 1967.

[24] 24. Hirano A, Dembitzer HM - Morphology of normal central myelinated axons. In Waxman SG (ed): Physiology and Pathobiology of Axons. Raven, New York, 1978, pg 65.

[25] 25. Kelly WR, Blakemore WF, Jagelman S, Webb HE - Demyelination induced in mice by avirulent Semliki Forest Virus: II. An ultrastructural study of focal demyelination in the brain. Neuropathol Appl Neurobiol 8: 43, 1982.

[26] 26. Kusaka H, Hirano A, Bornstein MB, Raine CS - Fine structure of astrocyte processes during serum-induced demyelination in vitro. J Neurol Sci 69: 255, 1985.

[27] 27. Lampert PW - Autoimmune and virus-induced demyelinating diseases: a review. Am J Pathol 91 :176, 1978.

[28] 28. Lampert PW - Fine structure of the demyelinating process. In Hallpike JF, Adams CWM, Tourtellotte WW (eds): Multiple Sclerosis: Pathology, Diagnosis and Management. Chapman, London, 1983, pg 29.

[29] 29. Lampert PW, Carpenter S - Electron microscopic studies on the vascular permeability and the mechanism of demyelination in experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 24: 11, 1965.

[30] 30. Leibowitz S, Hughes RAC - Immunology of the Nervous System. Edward Arnold, London, 1983.

[31] 31. Ludwin SK - Central nervous system demyelination and remyelination in the mouse: an ultrastructural study of cuprizone toxicity. Lab Invest 39: 597, 1978.

[32] 32. Ludwin SK - Chronic demyelination inhibits remyelination in the central nervous system: an analysis of contributing factors. Lab Invest 43: 382, 1980.

[33] 33. Mirsky R, Winter J, Abney ER, Pruss RM, Gavrilovic J, Raff MC - Myelin-specific proteins and glycolipids in rat Schwann cells and oligodendrocytes in culture. J Cell Biol 84: 483, 1980.

[34] 34. McDonald WI - Remyelination in relation to clinical lesions in the central nervous system. Br Med Bull 30: 186, 1974.

[35] 35. Nagashima K - Ultrastructural study of myelinating cells and sub-pial astrocytes in developing rat spinal cord. J Neurol Sci 44 :1, 1979.

[36] 36. Peters A, Palay SL, Webster H deF - The Fine Structure of the Nervous System: the Neurons and Supporting Glia. WB Saunders, Philadelphia, 1976.

[37] 37. Powell HC, Lampert PW - Oligodendrocytes and their myelin-plasma membrane connections in JHM mouse hepatitis virus encephalomyelitis. Lab Invest 33: 440, 1975.

[38] 38. Prineas JW, Raine CS - Mechanism of myelin breakdown in multiple sclerosis. J Neuropathol Exp Neurol 38: 336, 1979.

[39] 39. Raine CS - Morphology of myelin and myelination. In Morell P (ed): Myelin. Ed 2. Plenum, New York, 1984, pg 1.

[40] 40. Raine CS, Hummelgard A, Swanson E, Bornstein MB - Multiple sclerosis: serum-induced demyelination in vitro. A light and electron microscopic study. J Neurol Sci 20: 127, 1973.

[41] 41. Toro I, Ruzsa P, Rohlich P - Ultrastructure of early phagocytic stages in sinus endothelial and Kupffer cells of the liver. Exp Cell Res 26: 601, 1962.

[42] 42. Vandevelde M, Zurbriggen A, Higgins RJ, Palmer D - Spread and distribution of viral antigen in nervous system canine distemper. Acta Neuropathol (Berlin) 67: 211, 1985.

[43] 43. Waxman SG - Conduction in normal and demyelinated axons. In Pearlman AL, Collins RC (eds): Neurological Pathophysiology. Oxford Univ Press, 1984, pg 13.

[44] 44. Weller RO - Experimental demyelinating diseases and their relevance to the study of multiple sclerosis. In Matthew WB (ed): McAlpine's Multiple Sclerosis. Churchill Livingstone, Edinburgh, 1985, pg 344.

[45] 45. Whitaker JN - Demyelinating diseases. In Pearlman AL, Collins RC (eds): Neurological Pathophysiology. Oxford Univ Press, 1984, pg 274.

[46] 46. Wisniewski H, Raine CS - An ultrastructural study of experimental demyelination and remyelination: V. Central and peripheral nervous system lesions caused by diphtheria toxin. Lab Invest 25 :73, 1971.

[47] 47. Wisniewski H, Bloom BR - Primary demyelination as a non-specific consequence of a cell-mediated immune reaction. J Exp Med 141: 346, 1975.

[48] 48. Wisniewski H, Raine CS, Kay WJ - Observations on viral demyelinating encephalomyelitis: canine distemper. Lab Invest 26: 589, 1972.