Abstract
Multiple sclerosis (MS) is a demyelinating disease characterized by the breakdown of the blood-brain barrier (BBB), and accumulation of inflammatory infiltrates in the central nervous system. Tight junctions are specialized cell-cell adhesion structures and critical components of the BBB that have previously been shown to be abnormally distributed in MS tissue. To evaluate whether experimental autoimmune encephalomyelitis (EAE) provides a suitable model for this aspect of MS disease, we examined the expression and distribution of ZO-1 over the course of disease in EAE. We observed a dramatic relocalization of ZO-1 which precedes overt clinical disease and correlates with the sites of inflammatory cell accumulation. Treatment of in vitro cultures of murine brain endothelial cells with components of EAE induction provided similar findings, with relocalization of ZO-1 and increased permeability of endothelial monolayers. BBB disruption in the EAE model appears to parallel disease progression in MS, with direct effects on the cerebrovascular endothelium, making it an ideal tool for future evaluation of tight junction breakdown and repair in MS-like pathology.
Copyright © 2010 Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blood-Brain Barrier / physiopathology*
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Brain / cytology
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Calcium-Binding Proteins / metabolism
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Capillary Permeability / physiology*
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Cell Adhesion Molecules / metabolism
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Cells, Cultured
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Dextrans / pharmacokinetics
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Disease Models, Animal
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Disease Progression
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Encephalomyelitis, Autoimmune, Experimental / chemically induced
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Encephalomyelitis, Autoimmune, Experimental / pathology*
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Encephalomyelitis, Autoimmune, Experimental / physiopathology*
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Endothelial Cells / physiology
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Female
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Gene Expression Regulation / physiology
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Glycoproteins / adverse effects
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Lipopolysaccharides / pharmacology
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Membrane Proteins / metabolism
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Mice
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Mice, Inbred C57BL
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Microfilament Proteins
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Myelin-Oligodendrocyte Glycoprotein
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Nerve Fibers, Myelinated / pathology
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Occludin
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Peptide Fragments / adverse effects
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Pertussis Toxin / adverse effects
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Phosphoproteins / metabolism
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Receptors, Cell Surface / metabolism
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Spinal Cord / pathology
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Tight Junctions / pathology
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Tight Junctions / physiology
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Zonula Occludens-1 Protein
Substances
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Aif1 protein, mouse
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Calcium-Binding Proteins
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Cell Adhesion Molecules
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Dextrans
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F11r protein, mouse
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Glycoproteins
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Lipopolysaccharides
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Membrane Proteins
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Microfilament Proteins
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Myelin-Oligodendrocyte Glycoprotein
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Occludin
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Ocln protein, mouse
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Peptide Fragments
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Phosphoproteins
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Receptors, Cell Surface
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Tjp1 protein, mouse
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Zonula Occludens-1 Protein
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myelin oligodendrocyte glycoprotein (35-55)
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Pertussis Toxin