This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Minagar, A. Articles by Alexander, J S. Search for Related Content PubMed PubMed Citation Articles by Minagar, A. Articles by Alexander, J S. Social Bookmarking                         What's this?

Blood-brain barrier disruption in multiple sclerosis

Departments of Neurology, Psychiatry and Anesthesiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA

J Steven Alexander

Departments of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA, jalexa{at}lsuhsc.edu

The blood-brain barrier (BBB) is a complex organization of cerebral endothelial cells (C EC), pericytes and their basal lamina, which are surrounded and supported by astrocytes and perivascular macrophages. C ollectively these cells separate and form the compartments of the cerebral vascular space and the cerebral interstitium under normal conditions. Without the BBB, the ‘interior milieu’ of the central nervous system (CNS) would be flooded by humoral neurotransmitters and formed blood elements that upset normal C NS functions and lead to vascular/neural injury. Dysregulation of the BBB and transendo thelial migration of activated leukocytes are among the earliest cerebrovascular abnormalities seen in multiple sclerosis (MS) brains and parallel the release of inflammatory cytokines/chemokines. Mechanisms for breakdown of the BBB in MS are incompletely understood, but appear to involve direct effects of these cytokines/chemokines on endothelial regulation of BBB components, as well as indirect cytokine/chemokine-dependent leukocyte mediated injury.

Unique endothelial structural features of the BBB include highly organized endothelial tight junctions, the absence of class II major histocompatibility complex, abundant mitochondria and a highly developed transport system in C EC. Exposure of endothelium to proinflammatory cytokines (IFN-g, TNF-a and IL-1b) interrupts the BBB by disorganizing cell-cell junctions, decreases the brain solute barrier, enhances leukocyte endothelial adhesion and migration as well as increases expression of class II MHC and promotes shedding of endothelial ‘microparticles’ (EMP). In this review we examine interactions between cytokines/chemokines, activated leukocytes, adhesion molecules and activated C EC in the pathogenesis of BBB failure in MS.

Key Words: blood-brain barrier • chemokine • cytokine • endothelial microparticle • multiple sclerosis

Multiple Sclerosis, Vol. 9, No. 6, 540-549 (2003)
DOI: 10.1191/1352458503ms965oa


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				Y. Sonobe, H. Takeuchi, K. Kataoka, H. Li, S. Jin, M. Mimuro, Y. Hashizume, Y. Sano, T. Kanda, T. Mizuno, et al. Interleukin-25 Expressed by Brain Capillary Endothelial Cells Maintains Blood-Brain Barrier Function in a Protein Kinase C{epsilon}-dependent Manner J. Biol. Chem., November 13, 2009; 284(46): 31834 - 31842. [Abstract] [Full Text] [PDF]

				B. Bahbouhi, L. Berthelot, S. Pettre, L. Michel, S. Wiertlewski, B. Weksler, I.-A. Romero, F. Miller, P.-O. Couraud, S. Brouard, et al. Peripheral blood CD4+ T lymphocytes from multiple sclerosis patients are characterized by higher PSGL-1 expression and transmigration capacity across a human blood-brain barrier-derived endothelial cell line J. Leukoc. Biol., November 1, 2009; 86(5): 1049 - 1063. [Abstract] [Full Text] [PDF]

				A. N. van den Pol Brain Trauma Enhances Transient Cytomegalovirus Invasion of the Brain Only in Mice That Are Immunodeficient J. Virol., January 1, 2009; 83(1): 420 - 427. [Abstract] [Full Text] [PDF]

				O. Handa, J. Stephen, and G. Cepinskas Role of endothelial nitric oxide synthase-derived nitric oxide in activation and dysfunction of cerebrovascular endothelial cells during early onsets of sepsis Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1712 - H1719. [Abstract] [Full Text] [PDF]

				C Iarlori, D Gambi, A Lugaresi, A Patruno, M Felaco, M Salvatore, L Speranza, and M Reale Reduction of free radicals in multiple sclerosis: effect of glatiramer acetate (Copaxone(R)) Multiple Sclerosis, July 1, 2008; 14(6): 739 - 748. [Abstract] [PDF]

				S. Jarius, P. Eichhorn, M. H. Albert, S. Wagenpfeil, M. Wick, B. H. Belohradsky, R. Hohlfeld, D. E. Jenne, and R. Voltz Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNF{alpha}-dependent and Fc-receptor-independent way Blood, May 15, 2007; 109(10): 4376 - 4382. [Abstract] [Full Text] [PDF]

				R. A. Adams, J. Bauer, M. J. Flick, S. L. Sikorski, T. Nuriel, H. Lassmann, J. L. Degen, and K. Akassoglou The fibrin-derived {gamma}377-395 peptide inhibits microglia activation and suppresses relapsing paralysis in central nervous system autoimmune disease J. Exp. Med., March 19, 2007; 204(3): 571 - 582. [Abstract] [Full Text] [PDF]

				L. Song, S. Ge, and J. S. Pachter Caveolin-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells Blood, February 15, 2007; 109(4): 1515 - 1523. [Abstract] [Full Text] [PDF]

				E. A. van Vliet, S. da Costa Araujo, S. Redeker, R. van Schaik, E. Aronica, and J. A. Gorter Blood-brain barrier leakage may lead to progression of temporal lobe epilepsy Brain, February 1, 2007; 130(2): 521 - 534. [Abstract] [Full Text] [PDF]

				H. Toft-Hansen, R. Buist, X.-J. Sun, A. Schellenberg, J. Peeling, and T. Owens Metalloproteinases Control Brain Inflammation Induced by Pertussis Toxin in Mice Overexpressing the Chemokine CCL2 in the Central Nervous System J. Immunol., November 15, 2006; 177(10): 7242 - 7249. [Abstract] [Full Text] [PDF]

				T. W. Phares, R. B. Kean, T. Mikheeva, and D. C. Hooper Regional differences in blood-brain barrier permeability changes and inflammation in the apathogenic clearance of virus from the central nervous system. J. Immunol., June 15, 2006; 176(12): 7666 - 7675. [Abstract] [Full Text] [PDF]

				J. E. Christensen, C. de Lemos, T. Moos, J. P. Christensen, and A. R. Thomsen CXCL10 Is the Key Ligand for CXCR3 on CD8+ Effector T Cells Involved in Immune Surveillance of the Lymphocytic Choriomeningitis Virus-Infected Central Nervous System J. Immunol., April 1, 2006; 176(7): 4235 - 4243. [Abstract] [Full Text] [PDF]

				H. Xu, R. Dawson, I. J. Crane, and J. Liversidge Leukocyte Diapedesis In Vivo Induces Transient Loss of Tight Junction Protein at the Blood-Retina Barrier Invest. Ophthalmol. Vis. Sci., July 1, 2005; 46(7): 2487 - 2494. [Abstract] [Full Text] [PDF]

				B. T. Hawkins and T. P. Davis The Blood-Brain Barrier/Neurovascular Unit in Health and Disease Pharmacol. Rev., June 1, 2005; 57(2): 173 - 185. [Abstract] [Full Text] [PDF]

				R. A. Adams, M. Passino, B. D. Sachs, T. Nuriel, and K. Akassoglou Fibrin Mechanisms and Functions in Nervous System Pathology Mol. Interv., June 1, 2004; 4(3): 163 - 176. [Abstract] [Full Text] [PDF]