| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Pharmacology, University of Arizona College of Medicine, Tucson, Arizona 85724-5050
Cerebral microvessel endothelial cells that form the blood-brain barrier (BBB) have tight junctions (TJ) that are critical for maintaining brain homeostasis and low permeability. Both integral (claudin-1 and occludin) and membrane-associated zonula occluden-1 and -2 (ZO-1 and ZO-2) proteins combine to form these TJ complexes that are anchored to the cytoskeletal architecture (actin). Disruptions of the BBB have been attributed to hypoxic conditions that occur with ischemic stroke, pathologies of decreased perfusion, and high-altitude exposure. The effects of hypoxia and posthypoxic reoxygenation in cerebral microvasculature and corresponding cellular mechanisms involved in disrupting the BBB remain unclear. This study examined hypoxia and posthypoxic reoxygenation effects on paracellular permeability and changes in actin and TJ proteins using primary bovine brain microvessel endothelial cells (BBMEC). Hypoxia induced a 2.6-fold increase in [14C]sucrose, a marker of paracellular permeability. This effect was significantly reduced (~58%) with posthypoxic reoxygenation. After hypoxia and posthypoxic reoxygenation, actin expression was increased (1.4- and 2.3-fold, respectively). Whereas little change was observed in TJ protein expression immediately after hypoxia, a twofold increase in expression was seen with posthypoxic reoxygenation. Furthermore, immunofluorescence studies showed alterations in occludin, ZO-1, and ZO-2 protein localization during hypoxia and posthypoxic reoxygenation that correlate with the observed changes in BBMEC permeability. The results of this study show hypoxia-induced changes in paracellular permeability may be due to perturbation of TJ complexes and that posthypoxic reoxygenation reverses these effects.
endothelial cells; cytoarchitecture; blood-brain barrier; immunofluorescence
This article has been cited by other articles:
|
|
 |
|
  G. Schreibelt, G. Kooij, A. Reijerkerk, R. van Doorn, S. I. Gringhuis, S. van der Pol, B. B. Weksler, I. A. Romero, P.-O. Couraud, J. Piontek, et al. Reactive oxygen species alter brain endothelial tight junction dynamics via RhoA, PI3 kinase, and PKB signaling FASEB J, November 1, 2007; 21(13): 3666 - 3676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Fischer, T. Gerriets, C. Wessels, M. Walberer, S. Kostin, E. Stolz, K. Zheleva, A. Hocke, S. Hippenstiel, and K. T. Preissner Extracellular RNA mediates endothelial-cell permeability via vascular endothelial growth factor Blood, October 1, 2007; 110(7): 2457 - 2465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-L. Yeh, D.-Y. Lu, C.-J. Lin, H.-C. Liou, and W.-M. Fu Inhibition of Hypoxia-Induced Increase of Blood-Brain Barrier Permeability by YC-1 through the Antagonism of HIF-1{alpha} Accumulation and VEGF Expression Mol. Pharmacol., August 1, 2007; 72(2): 440 - 449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hom, M. A. Fleegal, R. D. Egleton, C. R. Campos, B. T. Hawkins, and T. P. Davis Comparative changes in the blood-brain barrier and cerebral infarction of SHR and WKY rats Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1881 - R1892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Koto, K. Takubo, S. Ishida, H. Shinoda, M. Inoue, K. Tsubota, Y. Okada, and E. Ikeda Hypoxia Disrupts the Barrier Function of Neural Blood Vessels through Changes in the Expression of Claudin-5 in Endothelial Cells Am. J. Pathol., April 1, 2007; 170(4): 1389 - 1397. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Bendfeldt, V. Radojevic, J. Kapfhammer, and C. Nitsch Basic Fibroblast Growth Factor Modulates Density of Blood Vessels and Preserves Tight Junctions in Organotypic Cortical Cultures of Mice: A New In Vitro Model of the Blood-Brain Barrier J. Neurosci., March 21, 2007; 27(12): 3260 - 3267. [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]
|
|
|
|
 |
|
 L. Krizanac-Bengez, M. Hossain, V. Fazio, M. Mayberg, and D. Janigro Loss of flow induces leukocyte-mediated MMP/TIMP imbalance in dynamic in vitro blood-brain barrier model: role of pro-inflammatory cytokines Am J Physiol Cell Physiol, October 1, 2006; 291(4): C740 - C749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Fleegal, S. Hom, L. K. Borg, and T. P. Davis Activation of PKC modulates blood-brain barrier endothelial cell permeability changes induced by hypoxia and posthypoxic reoxygenation Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2012 - H2019. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Veltkamp, D. A. Siebing, L. Sun, S. Heiland, K. Bieber, H. H. Marti, S. Nagel, S. Schwab, and M. Schwaninger Hyperbaric Oxygen Reduces Blood-Brain Barrier Damage and Edema After Transient Focal Cerebral Ischemia Stroke, August 1, 2005; 36(8): 1679 - 1683. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Brooks, B. T. Hawkins, J. D. Huber, R. D. Egleton, and T. P. Davis Chronic inflammatory pain leads to increased blood-brain barrier permeability and tight junction protein alterations Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H738 - H743. [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]
|
|
|
|
 |
|
 B. Wojciak-Stothard, L. Y. F. Tsang, and S. G. Haworth Rac and Rho play opposing roles in the regulation of hypoxia/reoxygenation-induced permeability changes in pulmonary artery endothelial cells Am J Physiol Lung Cell Mol Physiol, April 1, 2005; 288(4): L749 - L760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wen, D. D. Watry, M. C. G. Marcondes, and H. S. Fox Selective Decrease in Paracellular Conductance of Tight Junctions: Role of the First Extracellular Domain of Claudin-5 Mol. Cell. Biol., October 1, 2004; 24(19): 8408 - 8417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Brown, K. S. Mark, R. D. Egleton, and T. P. Davis Protection against hypoxia-induced blood-brain barrier disruption: changes in intracellular calcium Am J Physiol Cell Physiol, May 1, 2004; 286(5): C1045 - C1052. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Mark, A. R. Burroughs, R. C. Brown, J. D. Huber, and T. P. Davis Nitric oxide mediates hypoxia-induced changes in paracellular permeability of cerebral microvasculature Am J Physiol Heart Circ Physiol, January 1, 2004; 286(1): H174 - H180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Witt, K. S. Mark, S. Hom, and T. P. Davis Effects of hypoxia-reoxygenation on rat blood-brain barrier permeability and tight junctional protein expression Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2820 - H2831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Ray, A. J. Roberts, S. D. Lee, G. A. Farkas, C. Michlin, D. I. Rifkin, P. T. Ostrow, and J. A. Krasney Exercise delays the hypoxic thermal response in rats J Appl Physiol, July 1, 2003; 95(1): 272 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Brown, K. S. Mark, R. D. Egleton, J. D. Huber, A. R. Burroughs, and T. P. Davis Protection against hypoxia-induced increase in blood-brain barrier permeability: role of tight junction proteins and NF{kappa}B J. Cell Sci., February 15, 2003; 116(4): 693 - 700. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
