Skip to main content
SpringerLink
Log in

Chronic relapsing experimental allergic encephalomyelitis: its value as an experimental model for multiple sclerosis

  • Survey Of Progress
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Summary

Comparison of the pathohistology of chronic relapsing experimental allergic encephalomyelitis (CR-EAE) and multiple sclerosis (MS) reveals a close similarity. Thus, CR-EAE appears to be a valuable model for the study of pathogenetic factors leading to the formation of MS lesions, although the induction of the disease may be different (active sensitization with CNS antigens and adjuvant in CR-EAE versus unknown etiology in MS). CR-EAE furthermore mimicks the pathohistological patterns of other related human inflammatory demyelinating diseases (i.e., acute perivenous leukoencephalomyelitis and acute hemorrhagic leukoencephalomyelitis). The expression of an acute, predominantly inflammatory versus chronic inflammatory demyelinating disease in this model depends upon the time interval between sensitization and sampling of the animals. Recent evidence is discussed that a cooperation between cellular and humoral immune mechanisms, directed against multiple CNS antigens, is responsible for the formation of large demyelinated plaques in EAE and MS.

Zusammenfassung

Die neuropathologischen Veränderungen in Gehirn und Rückenmark von Tieren mit chronisch rezidivierender experimenteller allergischer Enzephalomyelitis (CR-EAE) entsprechen weitgehend denen der Multiplen Sklerose (MS). Obwohl Unterschiede in der Ätiologie beider Erkrankungen wahrscheinlich sind, erscheint die CR-EAE als geeignetes Modell zum Studium der Pathogenese der entzündlichen Entmarkungsherde der MS. Weiters können im Modell der CR-EAE auch die pathohistologischen Veränderungen anderer, akuter, entzündlicher Entmarkungserkrankungen, der akuten perivenösen Leukoenzephalomyelitis und der akuten hämorrhagischen Leukoenzephalomyelitis gefunden werden. Das Auftreten einer akuten Leukoenzephalomyelitis einerseits oder einer chronischen Entmarkungsenzephalitis andererseits hängt vom Zeitintervall zwischen Immunisation und der pathohistologischen Untersuchung der Tiere ab. Neuere Befunde weisen darauf hin, daß bei der CR-EAE sowohl zelluläre als auch humorale Immunmechanismen, gegen multiple ZNS-Antigene gerichtet, an der Pathogenese großer Entmarkungsherde beteiligt sind.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Alvord EC (1970) Acute disseminated encephalomyelitis and “allergic” neuroencephalopathies. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 9. Elsevier, New York, pp 500–571

    Google Scholar 

  2. Arnon R, Crisp E, Kelley R, Ellison GW, Myers LM, Tourtellotte WW (1980) Antiganglioside antibodies in multiple sclerosis. J Neurol Sci 46:179–186

    Google Scholar 

  3. Bauer HJ, Poser S, Ritter G (1980) Progress in multiple sclerosis research. Springer, Berlin Heidelberg New York

    Google Scholar 

  4. Bernard CCA (1976) Experimental autoimmune encephalomyelitis in mice: genetic control of susceptibility. J Immunogenet 3:263–274

    Google Scholar 

  5. Boese A (1980) Search for the cause of multiple sclerosis and other chronic diseases of the central nervous system. Verlag Chemie, Weinheim

    Google Scholar 

  6. Bornstein MB, Appel SH (1961) The application of tissue culture to the study of experimental “allergic” encephalomyelitis. I. Patterns of demyelination. J Neuropathol Exp Neurol 20:141–147

    Google Scholar 

  7. Bornstein MB, Appel SH (1965) Tissue culture studies of demyelination. Ann NY Acad Sci 122:280–286

    Google Scholar 

  8. Brosnan CF, Stoner GL, Bloom BR, Wisniewski HM (1977) Studies on demyelination by activated lymphocytes in the rabbit eye. II. Antibody dependent cell mediated demyelination. J Immunol 118:2103–2110

    Google Scholar 

  9. Brown AM, McFarlin DE, Raine CS (1981) Chronic relapsing EAE in the mouse. J Neuropathol Exp Neurol 40:320

    Google Scholar 

  10. Charcot JM (1968) Histologie de la sclerose en plaque. Gaz Hôp (Paris) 41:554–566

    Google Scholar 

  11. Dorfman SH, Fry JM, Silberberg DH, Grose C, Manning MC (1978) Cerebroside antibody titers in antisera capable of myelination inhibition and demyelination. Brain Res 147: 410–415

    Google Scholar 

  12. Dupouey P, Schuller E, Coulon-Morelec MJ (1972) Presence of antigalactodiglyceride antibodies in the serum of patients suffering from multiple sclerosis. In: Leibowitz U (ed) Progress in multiple sclerosis. Research and treatment. Academic Press, New York, pp 141–153

    Google Scholar 

  13. Ferraro A, Cazzullo CL (1948) Chronic experimental allergic encephalomyelitis in monkeys. J Neuropathol Exp Neurol 7:235–260

    Google Scholar 

  14. Ferraro A, Jervis G (1940) Experimental disseminated encephalopathy in the monkey. Arch Neurol 43:195–209

    Google Scholar 

  15. Fraenkel M, Jakob A (1913) Zur Pathologie der Multiplen Sklerose mit besonderer Berücksichtigung der akuten Formen. Z Ges Neurol Psychiatr 14:565–603

    Google Scholar 

  16. Fry JM, Weissbarth S, Lehrer GM, Bornstein MB (1974) Cerebroside antibody inhibits sulfatide synthesis and myelination and demyelinates in cord tissue cultures. Science 183:540–542

    Google Scholar 

  17. Ghatak NR, Hirano A, Doron Y, Zimmerman HH (1973) Remyelination in multiple sclerosis with peripheral type myelin. Arch Neurol 29:262–267

    Google Scholar 

  18. Ibrahim MZM, Adams CWM (1963) The relationship between enzyme activity and neuroglia in plaques of multiple sclerosis. J Neurol Neurosurg Psychiatry 26:101–110

    Google Scholar 

  19. Ibrahim MZM, Adams CWM (1965) The relations between enzyme activity and neuroglia in early plaques of multiple sclerosis. J Pathol Bacteriol 90:239–243

    Google Scholar 

  20. Itoyama Y, Sternberger NW, Webster H de F, Quarles RH, Cohen SR, Richardson EP (1980) Immunocytochemical observations on the distribution of myelin-associated glycoprotein and myelin basic protein in multiple sclerosis lesions. Ann Neurol 7:167–177

    Google Scholar 

  21. Jellinger K (1969) Einige morphologische Aspekte der Multiplen Sklerose. Wien Z Nervenheilkd [Suppl] II:12–37

    Google Scholar 

  22. Jervis GA, Koprowski H (1948) Experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 7:309–320

    Google Scholar 

  23. Karcher D, Lassmann H, Lowenthal A, Kitz K, Wisniewski HM (1982) Antibodies restricted heterogeneity in serum and cerebrospinal fluid of chronic relapsing experimental allergic encephalomyelitis. J Neuroimmunol 2:93–106

    Google Scholar 

  24. Keith AB, McDermott JR (1980) Optimum conditions for inducing chronic relapsing experimental allergic encephalomyelitis in guinea pigs. J Neurol Sci 46:353–364

    Google Scholar 

  25. Kies MW, Murphy JB, Alvord EC (1960) Fractionation of guinea pig brain proteins with encephalitogenic activity. Fed Proc 19:207

    Google Scholar 

  26. Kristensson K, Wisniewski HM (1977) Chronic relapsing experimental allergic encephalomyelitis. Studies in vascular permeability changes. Acta Neuropathol (Berl) 39:189–194

    Google Scholar 

  27. Lampert PW (1965) Demyelination and remyelination in experimental allergic encephalomyelitis. J Neuropathol Exp Neurol 24:371–385

    Google Scholar 

  28. Lampert PW, Kies MW (1967) Mechanism of demyelination in allergic encephalomyelitis of guinea pigs. An electron microscopic study. Exp Neurol 18:210–223

    Google Scholar 

  29. Lassmann H (1983) A comparative neuropathology of chronic experimental allergic encephalomyelitis and multiple sclerosis. Neurology Series. Springer, Berlin Heidelberg New York (in press)

    Google Scholar 

  30. Lassmann H, Wisniewski HM (1978) Chronic relapsing EAE. Time course of neurological symptoms and pathology. Acta Neuropathol 43:35–42

    Google Scholar 

  31. Lassmann H, Wisniewski HM (1979) Chronic relapsing experimental allergic encephalomyelitis. Clinicopathological comparison with multiple sclerosis. Arch Neurol 36:490–497

    Google Scholar 

  32. Lassmann H, Wisniewski HM (1979) Chronic relapsing experimental allergic encephalomyelitis. Effect of age at the time of sensitization on clinical course and pathology. Acta Neuropathol 47:111–116

    Google Scholar 

  33. Lassmann H, Kitz K, Wisniewski HM (1980) Chronic relapsing experimental allergic encephalomyelitis in rats and guinea pigs—a comparison. In: Boese A (ed) Search for the cause of MS and other chronic diseases of the central nervous system. Verlag Chemie, Weinheim, pp 96–104

    Google Scholar 

  34. Lassmann H, Kitz K, Wisniewski HM (1980) Structural variability of demyelinating lesions in different models of subacute and chronic experimental allergic encephalomyelitis. Acta Neuropathol 51:191–201

    Google Scholar 

  35. Lassmann H, Kitz K, Wisniewski HM (1981) Ultrastructural variability of demyelinating lesions in experimental allergic encephalomyelitis and multiple sclerosis. Acta Neuropathol [Suppl] VII:173–175

    Google Scholar 

  36. Lassmann H, Budka H, Schnaberth G (1981) Inflammatory demyelinating polyradiculitis in a patient with multiple sclerosis. Arch Neurol 38:99–102

    Google Scholar 

  37. Lassmann H, Kitz K, Wisniewski HM (1981) In vivo effect of sera from animals with chronic relapsing experimental allergic encephalomyelitis on central and peripheral myelin. Acta Neuropathol 55:297–306

    Google Scholar 

  38. Lassmann H, Schwerer B, Kitz K, Egghart M, Bernheimer H (1982) Pathogenetic aspects of demyelinating lesions in chronic relapsing experimental allergic encephalomyelitis: possible interaction of cellular and humoral immune mechanisms. Prog Brain Res (in press)

  39. Lassmann H, Stemberger H, Kitz K, Wisniewski HM (1983) In vivo demyelinating activity of sera from animals with chronic experimental allergic encephalomyelitis: antibody nature of the demyelinating factors and the role of complement. J Neurol Sci (in press)

  40. Madrid RE, Wisniewski HM, Iqbal K, Pullakart RK, Lassmann H (1981) Relapsing experimental allergic encephalomyelitis induced with isolated myelin and with myelin basic protein plus myelin lipids. J Neurol Sci 50:399–411

    Google Scholar 

  41. Marburg O (1906) Die sogenannte „akute Multiple Sklerose“. Jahrb Psychiatr 27:211–312

    Google Scholar 

  42. McFarlin DE, Blank SE, Kibler RF (1974) Recurrent experimental allergic encephalomyelitis in the Lewis rat. J Immunol 113:712–715

    Google Scholar 

  43. Mehta PD, Lassmann H, Wisniewski HM (1981) Immunologic studies of chronic relapsing EAE in guinea pigs: similarities to multiple sclerosis. J Immunol 127:334–338

    Google Scholar 

  44. Morgan IM (1946) Allergic encephalomyelitis in monkeys in response to injection of normal monkey cord. J Bacteriol 51:614–615

    Google Scholar 

  45. Niedieck B (1975) On a glycolipid hapten of myelin. Prog Allergy 18:353–422

    Google Scholar 

  46. Ortiz-Ortiz L, Weigle WO (1976) Cellular events in the induction of experimental allergic encephalomyelitis in rats. J Exp Med 144:604–616

    Google Scholar 

  47. Panitch H, Ciccone C (1981) Induction of recurrent experimental allergic encephalomyelitis with myelin basic protein. Ann Neurol 9:433–438

    Google Scholar 

  48. Paterson PY (1960) Transfer of allergic encephalomyelitis in rats by means of lymph node cells. J Exp Med 111:119–135

    Google Scholar 

  49. Paterson PY, Jacobs AF, Coia EM (1965) Complement-fixing antibrain antibodies and allergic encephalomyelitis. II. Further studies concerning their protective role. Ann NY Acad Sci 124:292–298

    Google Scholar 

  50. Peters G (1935) Zur Frage der Beziehungen zwischen der disseminierten, nicht eitrigen Enzephalomyelitis und der Multiplen Sklerose. Z Ges Neurol Psychiatr 153:356–384

    Google Scholar 

  51. Pette H (1928) Über die Pathogenese der Multiplen Sklerose. Dtsch Z Nervenheilkd 105:76–132

    Google Scholar 

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

    Google Scholar 

  53. 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 

  54. Raine CS, Scheinberg L, Waltz JM (1981) Multiple sclerosis: oligodendrocyte survival and proliferation in an active established lesions. Lab Invest 45:534–546

    Google Scholar 

  55. Ravkina L, Rogova V, Lazarenko L (1978) Chronic experimental allergic encephalomyelitis in rhesus monkeys and its modification by treatment. J Neurol Sci 38:281–293

    Google Scholar 

  56. Rivers TM, Schwendtker FF (1935) Encephalomyelitis accampanied by myelin destruction experimentally produced in monkeys. J Exp Med 61:689–702

    Google Scholar 

  57. Rivers TM, Sprunt DH, Berry GP (1933) Observation on attempts to produce acute disseminated encephalomyelitis in monkeys. J Exp Med 58:39–53

    Google Scholar 

  58. Roboz-Einstein E, Robertson DM, Di Caprio JM, Moore W (1962) The isolation from bovine spinal cord of a homogenous protein with encephalitogenic activity. J Neurochem 9:353–361

    Google Scholar 

  59. Rossolimo GJ (1904) Multiple Sklerose. In: Flatau E, Jacobsohn L, Minor L (Hrsg) Handbuch der Pathologischen Anatomie des Nervensystems. Karger, Berlin, S 691–698

    Google Scholar 

  60. Ryberg B (1978) Multiple specifities of antibrain antibodies in multiple sclerosis and chronic myelopathy. J Neurol Sci 38:357–382

    Google Scholar 

  61. Saida T, Silberberg DH, Fry JM, Manning MC (1977) Demyelinating anti-galactocerebroside antibodies in EAN and EAE. J Neuropathol Exp Neurol 36:627

    Google Scholar 

  62. Schmidt RM (1979) Multiple Sklerose. VEB Gustav Fischer Verlag, Jena

    Google Scholar 

  63. Seitelberger F, Jellinger K, Tschabitscher H (1958) Zur Genese der akuten Entmarkungsenzephalitis. Wien Klin Wochenschr 70:453–459

    Google Scholar 

  64. Shiraki H, Yonezawa T, Kuroiwa Y (1976) The aetiology and pathogenesis of the demyelinating diseases. Japan Science Press, Tokyo

    Google Scholar 

  65. 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 

  66. Stone SH, Lerner EM (1965) Chronic disseminated allergic encephalomyelitis in guinea pigs. Ann NY Acad Sci 122:227–241

    Google Scholar 

  67. Stone SH, Lerner EM, Goode JH (1969) Acute and chronic autoimmune encephalomyelitis: age, strain and sex dependency. The importance of the source of antigen. Proc Soc Exp Biol Med 132:341–344

    Google Scholar 

  68. Strähuber A (1903) Über Degenerations- und Proliferationsvorgänge bei Multipler Sklerose des Nervensystems, nebst Bemerkungen zur Aetiologie und Pathogenese der Erkrankung. Zieglers Beitr Pathol Anat Allg Pathol 33:409–480

    Google Scholar 

  69. Suzuki K, Andrews JM, Waltz JM, Terry RD (1969) Ultrastructural studies of multiple sclerosis. Lab Invest 30:444–454

    Google Scholar 

  70. Tabira T, Itoyama Y, Kuroiwa Y (1982) Continuous antigenic stimulation in chronic relapsing EAE. Abstr IX. Int Congr Neuropathol, Vienna, p 134

    Google Scholar 

  71. Traugott U, Stone SH, Raine CS (1978) Experimental allergic encephalomyelitis: Migration of early T cells from the circulation to the CNS. J Neurol Sci 36:55–61

    Google Scholar 

  72. Traugott U, Stone SH, Raine CS (1979) Chornic relapsing experimental allergic encephalomyelitis: Correlation of circulating lymphocyte fluctuation with disease activity in suppressed and unsuppressed animals. J Neurol Sci 41:17–29

    Google Scholar 

  73. Traugott U, Shevach E, Chiba I, Stone SH, Raine CS (1982) Chronic relapsing experimental allergic encephalomyelitis: identification and dynamics of T and B cells within the central nervous system. Cell Immunol 68:261–275

    Google Scholar 

  74. Uchimura I, Shiraki H (1957) A contribution of the classification and the pathogenesis of demyelinating encephalomyelitis. J Neuropathol Exp Neurol 16:139–208

    Google Scholar 

  75. Vinken PJ, Bruyn GW (1970) Handbook of clinical neurology, vol 9. Elsevier, New York

    Google Scholar 

  76. Waksman BH, Morrison LR (1951) Tuberkulin type sensitivity to spinal cord antigen in rabbits with isoallergic encephalomyelitis. J Immunol 66:421–444

    Google Scholar 

  77. Weiner HL, Hauser SL (1982) Neuroimmunology. I. Immunoregulation in neurological disease. Ann Neurol 11:437–449

    Google Scholar 

  78. Wisniewski HM, Keith AB (1977) Chronic relapsing experimental allergic encephalomyelitis—an experimental model of multiple sclerosis. Ann Neurol 1:144–148

    Google Scholar 

  79. Wisniewski HM, Lassmann H (1980) Chronic relapsing EAE: its application to study of human inflammatory demyelinating diseases. In: Bauer H, Poser S, Ritter G (eds) Progress in multiple sclerosis research. Springer, Berlin Heidelberg New York, pp 11–17

    Google Scholar 

  80. Wisniewski HM, Prineas J, Raine CS (1969) An ultrastructural study of experimental demyelination and remyelination in the peripheral and central nervous system. I. Acute experimental allergic encephalomyelitis. Lab Invest 21:105–118

    Google Scholar 

  81. Wisniewski HM, Brosnan CF, Bloom RR (1980) Bystander and antibody dependent cell-mediated demyelination. In: Davison AN, Cuzner MC (eds) The suppression of experimental allergic encephalomyelitis and multiple sclerosis. Academic Press, London, pp 45–58

    Google Scholar 

  82. Wisniewski HM, Lassmann H, Brosnan CF, Mehta PD, Lidsky AA, Madrid RE (1982) Multiple sclerosis: immunological and experimental aspects. In: Matthews WB, Glaser GH (eds) Recent advances in clinical neurology, vol 3. Churchill-Livingstone, London, pp 95–124

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neurological Institute, University of Vienna, Schwarzspanierstr. 17, A-1090, Vienna, Austria

    Hans Lassmann

Authors
  1. Hans Lassmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by Austrian Science Research Fund, Project S25/07

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lassmann, H. Chronic relapsing experimental allergic encephalomyelitis: its value as an experimental model for multiple sclerosis. J Neurol 229, 207–220 (1983). https://doi.org/10.1007/BF00313549

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00313549

Key words

Search

Navigation