Biology of the repair of central nervous system demyelinated lesions: an appraisal

Biologia da reparação de lesões desmielinizantes do sistema nervoso central: uma avaliação

Biology of the repair of central nervous system demyelinated lesions: an appraisal

Biologia da reparação de lesões desmielinizantes do sistema nervoso central: uma avaliação

L. A. V Peireira^I; M. A. Cruz-Höfling^II; M. S. J. Dertkigil^III; D. L. Graça^IV

^IAssistant Professor DHE/IB/UNICAMP

^IIAssociate Professor DHE/1B/UN1CAMP

^IIIGraduate Student of Medical Sciences/UNICAMP

^IVProfessor of Pathology DP/ CCS/UFSM

ABSTRACT

The integrity of myelin sheaths is maintained by oligodendrocytes and Schwann cells respectively in the central nervous system (CNS) and in the peripheral nervous system. The process of demyelination consisting of the withdrawal of myelin sheaths from their axons is a characteristic feature of multiple sclerosis, the most common human demyelinating disease. Many experimental models have been designed to study the biology of demyelination and remyelination (repair of the lost myelin) in the CNS, due to the difficulties in studying human material. In the ethidium bromide (an intercalating gliotoxic drug) model of demyelination, CNS remyelination may be carried out by surviving oligodendrocytes and/or by cells differentiated from the primitive cell lines or either by Schwann cells that invade the CNS. However, some factors such as the age of the experimental animals, intensity and time of exposure to the intercalating chemical and the topography of the lesions have marked influence on the repair of the tissue.

Key words: toxic demyelination, remyelination, central nervous system, peripheral nervous system.

RESUMO

A integridade da bainha de mielina é fornecida pelos oligodendrócitos e pelas células de Schwann, no sistema nervoso central (SNC) e no sistema nervoso periférico, respectivamente. O fenômeno de desmielinização refere-se à remoção das bainhas de mielina de axônios e este fato é característico na esclerose múltipla, a doença desmielinizante do SNC mais comum no homem. Muitos modelos experimentais têm sido utilizados para o estudo da biologia da desmielinização e remielinização no SNC, face à dificuldade de estudo de material humano. No modelo experimental da droga intercalate, gliotóxica, brometo de etídio, a remielinização do SNC pode ser efetuada por oligodendrócitos sobreviventes à lesão e/ou oriundos de diferenciação de linhagens celulares mais primitivas e por células de Schwann que invadem o SNC. No entanto, fatores como a idade dos animais, a intensidade, e o tempo de exposição ao agente intercalante e a topografia da lesão influenciam significativamente a reparação da lesão.

Palavras-chave: desmielinização tóxica, remielinização, sistema nervoso central, sistema nervoso periférico.

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Acknowledgements - This study was benefited in part by a Grant-in Aid for Scientific Research (project number 93/4994-5) from FAPESP (São Paulo, Brazil). The authors wish to thank Mrs. Adriane S.Sprogis, Antonia F. Lima (UNICAMP) and Iara E. Flores (UFSM) for the technical assistance.

33. Wolswijk G, Noble M. Cooperation between PDGF and FGF converts slowly dividing 0-2A"*"' progenitor cells to rapidly dividing cells with characteristics of 0-2A *«*»•»> progenitor cells. J Cell Biol 1992; 118:889-900.

Aceite:9-janeiro-1996.

Study carried out in the Department of Histology and Embryology (DHE), Institute of Biology (IB), State University of Campinas (UNICAMP) and Department of Pathology (DP), Health Science Center (CCS), Federal University of Santa Maria (UFSM)

Dr. Luís Antônio Violin Pereira - Department of Histology and Embryology, IB/UNICAMP - P.O.Box 6109 -13083-970 Campinas SP - Brazil. FAX [phone].

• 1. Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. Molecular biology of the ceil. Ed. 3, New York-.Garland, 1994.
• 2. Allen IV, Kirk J. Demyelinating diseases. In Adams JH, Duchen LW (eds). Greenfields neuropathology. London:Edward Arrnold, 1992:447-520.
• 3. Bertolotto A, Rocca G, Schiffer D. Chondroitin 4-sulfate proteoglycan forms an extracellular network in human and rat central nervous system. J Neurol Sci 1990;100:113-123.
• 4. Blakemore WF. Remyelination by Schwann cells of axons demyelinated by intraspinal injection of 6-aminonicotinamide in the rat. J Neurocytol. 1975;4:745-757.
• 5. Blakemore WF. Myelination, demyelination and remyelination in the CNS. In Cavanagh JB, Smith WT (eds). Recent advances in neuropathology. Edinburg:Churchill Livingstone,1982:53-81.
• 6. Blakemore WF, Eames RA, Smith KJ, McDonald WI. Remyelination in the spinal cord of the cat following intraspinal injections of lysolecithin. J Neurol Sci 1977;33:31-43.
• 7. Bunge M, Bunge, RP, Ris, H. Ultrastructural study of remyelination in an experimental lesion in adult cat spinal cord. J Biophys BiochemCytoI 1961; 10:67-94.
• 8. Eng LF, Yu ACH, Lee YL. Astrocytic response to injury. Progr Brain Res 1992;94:353-365.
• 9. Graça DL. Investigation into ethidium bromide induced demyelination in the central nervous system. PhD Thesis, University of Cambridge. Cambridge, 1986.
• 10. Graça DL. Mielinização, desmielinização e remielinização no sistema nervoso central. Arq Neuropsiquiatr 1988;46:292-297.
• 11. Graça DL. Desmielinização tóxica do sistema nervoso central. II. Aspectos biológicos das células de Schwann observados durante o processo de reparação do tecido. Arq Neuropsiquiatr 1989;47:268-273.
• 12. Graça DL, Blakemore WF. The formation of intracytoplasmic "scrolls" following local injections of ethidium bromide. Neuropathol Appl Neurobiol 1985; 11:73.
• 13. Graça DL, Blakemore WF. Delayed remyelination in the rat spinal cord following ethidium bromide injection. Neuropathol Appl Neurobiol 1986;12:593-605.
• 14. Itoyama Y, Webster HF, Richardson EP Jr, Trapp BD. Schwann cell remyelination of demyelinated axons in spinal cord multiple sclerosis lesions. Ann Neurol 1983;14:339-346.
• 15. Kelly WR, Blakemore WF, Jagelman S, Webb S. Demyelination induced in mice by avirulent Semliki Forest virus. II. An ultrastructural study of focal demyelination in the rat brain. Neuropathol Appl Neurobiol 1982;8:43-53.
• 16. Kusaka H, Hirano A, Bornstein MB, Raine CS. Fine structure of astrocytic processes during serum-induced demyelination in vitro. J Neurol Sci 1985;69:255-267.
• 17. Lampert P, Carpenter S. Electron microscopic studies on the vascular permeability and the mechanism of demyelination in the experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 1965;24:11 -24.
• 18. Linpton HL. Theiler's virus infection in mice: an unusual biphasic disease process leading to demyelination. Infec Immun 1975;11:1147-1155.
• 19. Ludwin SK. Central nervous system demyelination and remyelination in the mouse: an ultrastructural study of cuprizone toxicity. Lab Invest 1978;39:597-612.
• 20. Moore K. Embriologia Clínica Ed3, Rio de Janeiro:Interamericana 1984;354-388.
• 21. McCarthy GF, Leblon CP. Radioautographic evidence for slow astrocyte turnover and modest oligodendrocyte production in the corpus callosum of adult mice infused with 3H-thymidine. J Comp Neurol 1988; 271:589-603.
• 22. Noble M, Ataliotis P, Barnett SC, Bevan K, Bogler O, Groves A, Jat P, Wolswijk G, Wren D. Development, regeneration, and neoplasia of glia cells in the central nervous system. Ann NY Acad Sci 1991 ;633:35-47.
• 23. Pereira LAV. Efeitos do brometo de eu'dio no tronco cerebral de ratos Wistar: aspectos morfoiógicos relacionados aos processos de desmielinização e remielinização do sistema nervoso central. Tese de Mestrado. Universidade Estadual de Campinas. Campinas, 1994.
• 24. Pereira LAV, Graça DL. Biologia da neuroglia. Anais XLH Reunião Anual SBPC 1990; 1:427-429.
• 25. Pereira LAV, Graça DL, Dertkigil MSJ, Cruz-Hõfling MA. Dynamics of remyelination in the brain after exposure to ethidium bromide, 1995. Submitted for publication in J Neurophatol Appl Neurobiol.
• 26. Raff MC, Abney ER, Miller RH. Two glial cell lineages diverge prenatally in the rat opric nerve. Dev Biol 1984; 106:53-60.
• 27. Raff MC. Glial cell diversification in the rat optic nerve. Science 1989;243:1450-1455.
• 28. Raine CS. On the occurrence of Schwann cells within the normal central nervous system. J Neurocytology 1976,5:371 -380.
• 29. Raine CS. Demyelination diseases. In Davis RL et al (eds). Textbook of neuropathology. Baltimore:WilIiams & Wilkins, 1985:468-547.
• 30. Raine CS, Scheinberg L, Waltz JM. Multiple sclerosis: oligodendrocyte survival and proliferation in an active established lesion. Lab Invest 1981,45:534-546.
• 31. Reynolds R, Wilkin GP. Cellular reaction to an acute demyelinating/remyelinating lesion of the rat brain stem: localization of G_a, ganglioside immunoreuctivity. J Neurosci Res 1993;36:405-422.
• 32. Suzuki K, Zaragoren JC. Degeneration of oligodendroglia in the central nervous system of rats treated with AY9944 or triparanol. Lab Invest 1974;31:503-505.
• 34. Yajima K, Suzuki K. Demyelination and remyelination in the rat central nervous system following ethidium bromide injection. Lab Invest 1979;41:385-392.

Publication Dates

• Publication in this collection
  06 Dec 2010
• Date of issue
  June 1996