title: Astrocyte mediated modulation of blood-brain barrier permeability does not correlate with a loss of tight junction proteins from the cellular contacts.
abstract: In the central nervous system (CNS) complex endothelial tight junctions (TJs) form a restrictive paracellular diffusion barrier, the blood-brain barrier (BBB). Pathogenic changes within the CNS are frequently accompanied by the loss of BBB properties, resulting in brain edema. In order to investigate whether BBB leakiness can be monitored by a loss of TJ proteins from cellular borders, we used an in vitro BBB model where brain endothelial cells in co-culture with astrocytes form a tight permeability barrier for 3H-inulin and 14C-sucrose. Removal of astrocytes from the co-culture resulted in an increased permeability to small tracers across the brain endothelial cell monolayer and an opening of the TJs to horseradish peroxidase as detected by electron microscopy. Strikingly, opening of the endothelial TJs was not accompanied by any visible change in the molecular composition of endothelial TJs as junctional localization of the TJ-associated proteins claudin-3, claudin-5, occludin, ZO-1 or ZO-2 or the adherens junction-associated proteins beta-catenin or p120cas did not change. Thus, opening of BBB TJs is not readily accompanied by the complete loss of the junctional localization of TJ proteins.
authors: Max Planck Institute for Physiological and Clinical Research, Bad Nauheim, Germany.
authors: Stefan
authors: S
authors: Hamm
authors: Bénédicte
authors: B
authors: Dehouck
authors: Jörg
authors: J
authors: Kraus
authors: Karen
authors: K
authors: Wolburg-Buchholz
authors: Hartwig
authors: H
authors: Wolburg
authors: Werner
authors: W
authors: Risau
authors: Roméo
authors: R
authors: Cecchelli
authors: Britta
authors: B
authors: Engelhardt
authors: Marie-Pierre
authors: MP
authors: Dehouck
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000502:physiology* / Q000648:ultrastructure; D051177:Catenins; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D062465:Claudin-3; D062507:Claudin-5; D003598:Cytoskeletal Proteins / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology* / Q000648:ultrastructure; D006735:Horseradish Peroxidase / Q000737:chemistry / Q000493:pharmacokinetics; D007444:Inulin / Q000737:chemistry / Q000493:pharmacokinetics; D008565:Membrane Proteins / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D062793:Occludin; D010539:Permeability; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D013395:Sucrose / Q000737:chemistry / Q000493:pharmacokinetics; D019108:Tight Junctions / Q000502:physiology* / Q000648:ultrastructure; D015534:Trans-Activators / Q000378:metabolism; D062827:Zonula Occludens-2 Protein; D051176:beta Catenin; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D015815:Cell Adhesion Molecules; D062465:Claudin-3; D062507:Claudin-5; C568124:Cldn3 protein, rat; C491510:Cldn5 protein, rat; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D062793:Occludin; C568987:Ocln protein, rat; D010750:Phosphoproteins; D015534:Trans-Activators; D062827:Zonula Occludens-2 Protein; D051176:beta Catenin; D013395:Sucrose; D007444:Inulin; D006735:Horseradish Peroxidase; D000095002:Delta Catenin