The Blood-Brain Barrier in Immune Mediated Diseases of the Central Nervous System

  • Shmuel Miron
  • Anat Achiron


The blood-brain barrier (BBB) is essential for the maintenance and regulation of the neural microenvironment. The term BBB describes a complex cellular system of, astrocytes, perivascular macrophages, a basal lamina and endothelial cells that controls the exchange of molecules between the brain parenchima and the rest of the body. Astrocytes, which encircle the cerebral endothelial cells (CEC) with their extended foot processes, have a role in the induction and maintenance of BBB properties (Rubin and Staddon, 1999). The close contact between cells and astrocyte-derived factors probably mediate these effects. Furthermore, factors found in the extracellular matrix shared by astrocytes and endothelial cells seem to be involved in the maintenance of barrier properties (Engelhardt, 1997). The CEC are characterised by an extremely low rate of transcytotic transport via vesicles, and a restrictive paracellular diffusion barrier realized by the tight junctions coupling the CEC. These tight junctions, functionally connected to cytoskeletal proteins, are effective in restricting entry of proteins and cells from the blood into the brain and cerebrospinal fluid. The BBB-tight junctions are morphologically similar to epithelial tight junctions, but differ in being highly sensitive to changes in the endothelial environment (De Vries et al., 1997).


Multiple Sclerosis Tight Junction Experimental Autoimmune Encephalomyelitis Multiple Sclerosis Patient Multiple Sclerosis Lesion 
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  1. Antel, J., A., Prat 2000. Antigen and superantigen presentation in the human CNS. J Neuroimmonol 107: 118–123.CrossRefGoogle Scholar
  2. Archelos, J., and H. P. Hartung 2000. Pathogenetic role of autoantibodies in neurological diseases. Trends Neurosci. 23, 317–327.CrossRefPubMedGoogle Scholar
  3. Constant, C., (1994) Pathogenesis of multiple sclerosis. Lancet 343: 271–275.CrossRefGoogle Scholar
  4. DeVries, H., Bloom-Roosemalen, M., VanOosten, M., DeBoer, A., VanBerkel, T., D. Breimer, J., Kuiper 1996. The influence of cytokines on the integrity of the blood-brain barrier in vitro. J neuroimmunol. 64: 37–43.CrossRefGoogle Scholar
  5. Gay, D., and M. Esiri 1991. Blood-brain barrier damage in acute multiple sclerosis plaques. Brain 114: 557–572.CrossRefPubMedGoogle Scholar
  6. Grossman, R., Gonzales-Searano, F., S. Atlas. 1986 Multiple sclerosis: Gadolinium enhancement in MR imaging. Radiology; 161: 721–725.PubMedGoogle Scholar
  7. Kieseier, B., Storch, M., Archelos, J., Martino, G., H. P. Hartung 1999. Effector pathways in immune mediated central nervous system demyelination. Curr Opin Neurol 12: 323–336.CrossRefPubMedGoogle Scholar
  8. Lassman, H., 1998. Pathology of multiple sclerosis. In Compston, A., Ebers, G., Lassman, H., McDonald, I., Matthews, B., and H., Wekerle (eds) McAlpine’s Multiple Sclerosis. London, Churchill Livingstone 323–358.Google Scholar
  9. Lee, MA, Palace J., Stabler, G., Ford, J., Gearing, A., Miller K. 1999. Serum gelatinase B, TIMP-1 and TIMP-2 levels in multiple sclerosis: a longitudinal clinical and MRI study. Brain 122: 191–197.CrossRefPubMedGoogle Scholar
  10. Merril, J., and E., Benveniste 1996. Cytokines in inflammatory brain lesions: helpful and harmful. Trends Neurosci 19, 331–338.CrossRefGoogle Scholar
  11. Miller, DH. 1992 High dose steroids in acute relapse of MS: MRI evidence for a possible mechanism of therapeutic effect. J Neurol Neurosurg; 55: 450.CrossRefGoogle Scholar
  12. Owens, T., Sriram, S. (1995) The immunology of multiple sclerosis and its animal model, experimental allergic encephalomyelitis. Neurologic clinics 13: 51–73.PubMedGoogle Scholar
  13. Seeldrayers, P., Syha, J., Morrissey, S.P. 1993. Magnetic resonance imaging investigation of blood-brain barrier damage in adoptive transfer experimental autoimmune encephalomyelitis. J Neuroimmunol 46; 199–206.CrossRefPubMedGoogle Scholar
  14. Rosenberg, G., Dencof, G., Correra, N., Reiners, M, Ford C., 1996. Effect of steroids on CSF matrix metalloproteinases in multiple sclerosis: relation to blood-brain barrier injury. Neurology 46: 1626–1632.CrossRefPubMedGoogle Scholar
  15. Rubin, L., and J. M. Staddon 1999. The cell biology of the Blood brain barrier. Annu.Rev. Neurosci. 22: 11–28.CrossRefPubMedGoogle Scholar
  16. Schmidt, S., 1999. Candidate autoantigens in multiple sclerosis. Multiple Sclerosis 5. 147–160.PubMedGoogle Scholar
  17. Smith, K., Kapoor, R., P. Felts 1999. Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathology 9: 69–92.CrossRefPubMedGoogle Scholar
  18. Von Andrian, U., and C. R. Mackay 2000. T-cell function and migration two sides of the same coin. New Engl J Med 343, 14, 1020–1034.Google Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Shmuel Miron
    • 1
  • Anat Achiron
    • 1
  1. 1.Neuroimmunology UnitSheba Medical CenterRamat-GanIsrael

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