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Time-Course of Demyelination and Blood-Brain Barrier Disruption in the Semliki Forest Virus Model of Multiple Sclerosis in the Mouse

  • A. M. Butt
  • S. Kirvell
  • R. D. Egleton
  • S. Amor
  • M. B. Segal
Part of the Advances in Behavioral Biology book series (ABBI, volume 46)

Summary

Increased permeability of the blood-brain barrier (BBB) is a prominent feature of multiple sclerosis (MS). However, the cause of the BBB leak and its role in the pathogenesis of MS are unknown. The present study addressed these questions in the Semliki Forest virus (SFV) model of MS in optic nerves of Balb/C mice, using the unidirectional transfer coefficient for [14C]mannitol as a measurement of BBB permeability and immunolabelling with anti-myelin basic protein (MBP) to determine the time-course and extent of demyelination. In SFV, there was a significant increase in BBB permeability in the optic nerve, prior to the onset of demyelination. The BBB leak was blocked by treatment with cimetidine, an antihistamine which acts on H2 receptors at the BBB. Preliminary results suggested that cimetidine may also have delayed the onset or reduced the level of demyelination in the optic nerve. The results support a role for histamine in BBB leak in the SFV mouse model of MS and indicate that BBB leak may be integral to the pathogenesis of demyelination.

Keywords

Multiple Sclerosis Optic Nerve Experimental Autoimmune Encephalomyelitis Experimental Allergic Encephalomyelitis Semliki Forest Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Résumé

Une plus grande perméabilité de la BHE est une importante caractéristique de la sclérose en plaques. Toutefois, on ne connait pas la cause de cette fuite de la BHE ni son rôle dans la pathogénicité de cette maladie. Cette étude avait pour but d’élucider ces questions au moyen du modèle virus semliki forest (SFV) de la sclérose en plaques dans les nerfs optiques des souris Balb/C, en utilisant le coefficient de transfert unidirectionnel du [14C]mannitol pour mesurer la perméabilité de la BHE, et l’immunomarquage par la protéine basique anti-myeline (MBP) pour définir le temps de passage et le degré de démyelinisation. Avec le SFV on notait une perméabilité accrue de la BHE dans le nerf optique, avant le début de la démyélinisation. La fuite de la BHE était bloquée par traitement parla cimétidine, un anti-histaminique qui agit sur les récepteurs 1-12 de la BHE. Les résultats préliminaires montrent que la cimétidine a abaissé également le taux de démyélinisation ou en a retardé le début dans le nerf optique. Ces résultats suggèrent que l’histamine joue un rôle dans la fuite de la BHE dans le modèle SFV-souris de sclérose en plaques et indique que celle-ci pourrait être le facteur essentiel de la pathogénèse de démyélinisation.

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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • A. M. Butt
    • 1
  • S. Kirvell
    • 1
  • R. D. Egleton
    • 2
  • S. Amor
    • 3
  • M. B. Segal
    • 1
  1. 1.Division of Physiology, U.M.D.S.St. Thomas’ HospitalLondonUK
  2. 2.Biomedical Sciences DivisionKing’s College LondonUK
  3. 3.Department of Immunolgy, Rayne Institute, U.M.D.S.St. Thomas’ HospitalLondonUK

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