Summary
Multiple sclerosis is considered to be an autoimmune demyelinating disease of the central nervous system. Damage to the blood-brain barrier, of which endothelial cells are the main constitutent, occurs in multiple sclerosis, probably due to immunological mechanisms. We report here the results of immune-mediated damage to these cells, produced by immunizing guinea pigs with an endothelial cell membrane fraction. The fraction was obtained from cerebral endothelial cells grown in vitro and was free from myelin basic protein. The immunized animals developed a chronic neurological illness with evidence of delayed hypersensitivity to the cell membrane fraction but not to myelin antigens. Histological examination of the brain in the acute stage showed mononuclear cell infiltrates aroud blood vessels, while in the chronic phase large areas of demyelination, especially in the periventricular region, were present. This bore a striking similarity to the brain in multiple sclerosis. This may prove to be a useful new animal model for the investigation of the human demyelinating disease.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Boman T (1964) Blood-brain barrier damage in multiple sclerosis. Supra-vital test observations. Acta Neurol Scand [suppl 10] 40:21–24
Brown WJ (1978) The capillaries in acute and subacute multiple sclerosis plaques — a morphometric analysis. Neurology 28:84–92
DeBault LE, Cancilla PA (1980) γ-Glutamyl transpeptidase in isolated brain endothelial cells: induction by lia cells in vitro. Science 207:653–655
Drewes LD, Lidinsky WA (1981) Studies of cerebral capillary endothelial membrane. Adv Exp Med Biol 131:17–27
Field EJ, Raine CS (1966) Experimental allergic encephalomyelitis. An electron-microscopic study. Am J Pathol 49:537–553b
Keith AB (1978) Sex difference in Lewis rats in the incidence of recurrent experimental allergic encephalomyelitis. Nature 272:824–825
Leammli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Lassmann H, Wiśniewski HM (1978) Chronic relapsing EAE. Time course of neurological symptoms and pathology. Acta Neuropathol (Berl) 43:35–42
Lassmann H, Wiśniewski HM (1979) Chronic relapsing experimental allergic encephalomyelitis. Clinicopathological comparison with multiple sclerosis. Arch Neurol 39:490–497
McMillan SA, Haire M, Middleton D (1980) Antibodies to lymphocytes and smooth muscle in the sera of patients with multiple sclerosis. Clin Immunol Immunopathol 16:374–385
Mrsũlja BB, Mrsũlja BT, Fujimoto T, Klatzo I, Spatz M (1976) Isolation of brain capillaries. A simplified technique. Brain Res 110:361–365
Orlowski M, Sessa G, Green JP (1974) γ-Glutamyl transpeptidase in brain capillaries: possible site of a blood brain barrier for amino acides. Science 184:66–68
Park WM, Gingrich RD, Dahle CE, Hoak JC (1985) Identification and characterization of an endothelial cell. Specific antigen with a monoclonal antibody. Blood 66:816–823
Paterson PY (1977) Autoimmune neurologic disease. Experimental animal system and implications for multiple sclerosis. In: Talal N (ed) Autoimmunity, genetics, immunologic, virologic, and clinical aspects. Academic Press, New York, pp 633–692
Poser CM, Behan PO (1982) Late onset of Guillain-Barré syndrome. J Neuroimmunol 3:27–42
Raine CS, Stone SH (1977) Animal model for multiple sclerosis. Chronic experimental allergic encephalomyelitis in inbred pigs. NY State J Med 77:1693–1696
Richert JR, Kies MW, Alvord EC Jr (1981) Enhanced transfer of experimental allergic encephalomyelitis with Lewis rat lymph node cells. J Neuroimmunol 1:195–203
Schimmel SD, Kent C, Bischoff R, Vagelos PR (1973) Plasma membranes from cultured muscle cells. Isolation procedure and separation of putative plasma-membrane marker enzymes. Proc Natl Acad Sci USA 70:3195–3199
Spatz M, Bembry J, Dodson RF, Hervonen H, Murray MR (1980) Endothelial cell cultures derived from isolated microvessels. Brain Res 191:577–582
Traugott U, Stone SH, Raine CS (1982) Chronic relapsing experimental autoimmune encephalomyelitis. Treatment with combination of myelin components promotes clinical and structural recovery. J Neurol Sci 56:65–73
Tsukada N, Ahmed SA, Behan WMH, Behan, PO (1986a) Similarities between the Forssman carotid syndrome and experimental allergic encephalomyelitis. Acta Neuropathol (Berl) 69:234–243
Tsukada N, Inoue I, Yanagisawa N, Behan WMH, Behan PO (1986b) Anti-endothelial cell antibody and immune complexes in the sera of animals with acute experimental allergic encephalomyelitis and chronic relapsing experimental perimental allergic encephalomyelitis. J Neuroimmunol 12:89–97
Wiśniewski HM, Keith AB (1977) Chronic relapsing experimental allergic encephalomyelitis. An experimental model of multiple sclerosis. Ann Neurol 1:144–148
Author information
Authors and Affiliations
Additional information
Supported by the Intractable Diseases Division, Public Health Bureau, Japanese Ministry of Health and Welfare, the grant (61570385) from Japanese Ministry of Education and the Multiple Sclerosis Society of Great Britain
Rights and permissions
About this article
Cite this article
Tsukada, N., Koh, CS., Yanagisawa, N. et al. A new model for multiple sclerosis: Chronic experimental allergic encephalomyelitis induced by immunization with cerebral endothelial cell membrane. Acta Neuropathol 73, 259–266 (1987). https://doi.org/10.1007/BF00686620
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00686620