A cell culture model of the blood-brain barrier

doi:10.1083/jcb.115.6.1725

This Article

	Full Text (PDF, 1329K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Rubin, L. L.
	Articles by Morales, J.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Rubin, L. L.
	Articles by Morales, J.


Social Bookmarking

	What's this?

ARTICLES

A cell culture model of the blood-brain barrier

LL Rubin, DE Hall, S Porter, K Barbu, C Cannon, HC Horner, M Janatpour, CW Liaw, K Manning and J Morales
Athena Neurosciences, Inc., South San Francisco, California 94080.

Endothelial cells that make up brain capillaries and constitute the blood-brain barrier become different from peripheral endothelial cells in response to inductive factors found in the nervous system. We have established a cell culture model of the blood-brain barrier by treating brain endothelial cells with a combination of astrocyte-conditioned medium and agents that elevate intracellular cAMP. These cells form high resistance tight junctions and exhibit low rates of paracellular leakage and fluid-phase endocytosis. They also undergo a dramatic structural reorganization as they form tight junctions. Results from these studies suggest modes of manipulating the permeability of the blood-brain barrier, potentially providing the basis for increasing the penetration of drugs into the central nervous system.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Forster, C., Burek, M., Romero, I. A., Weksler, B., Couraud, P.-O., Drenckhahn, D. (2008). Differential effects of hydrocortisone and TNF{alpha} on tight junction proteins in an in vitro model of the human blood-brain barrier. J. Physiol. 586: 1937-1949 [Abstract] [Full Text]
Schlegel, N., Burger, S., Golenhofen, N., Walter, U., Drenckhahn, D., Waschke, J. (2008). The role of VASP in regulation of cAMP- and Rac 1-mediated endothelial barrier stabilization. Am. J. Physiol. Cell Physiol. 294: C178-C188 [Abstract] [Full Text]
Tu, H., Kastin, A. J., Pan, W. (2007). Corticotropin-Releasing Hormone Receptor (CRHR)1 and CRHR2 Are Both Trafficking and Signaling Receptors for Urocortin. Mol. Endocrinol. 21: 700-711 [Abstract] [Full Text]
Zhang, Y., Li, C. S. W., Ye, Y., Johnson, K., Poe, J., Johnson, S., Bobrowski, W., Garrido, R., Madhu, C. (2006). Porcine Brain Microvessel Endothelial Cells as an in Vitro Model to Predict in Vivo Blood-Brain Barrier Permeability. Drug Metab. Dispos. 34: 1935-1943 [Abstract] [Full Text]
Josserand, V., Pelerin, H., de Bruin, B., Jego, B., Kuhnast, B., Hinnen, F., Duconge, F., Boisgard, R., Beuvon, F., Chassoux, F., Daumas-Duport, C., Ezan, E., Dolle, F., Mabondzo, A., Tavitian, B. (2006). Evaluation of Drug Penetration into the Brain: A Double Study by in Vivo Imaging with Positron Emission Tomography and Using an in Vitro Model of the Human Blood-Brain Barrier. J. Pharmacol. Exp. Ther. 316: 79-86 [Abstract] [Full Text]
Xu, H., Dawson, R., Crane, I. J., Liversidge, J. (2005). Leukocyte Diapedesis In Vivo Induces Transient Loss of Tight Junction Protein at the Blood-Retina Barrier. IOVS 46: 2487-2494 [Abstract] [Full Text]
Forster, C., Silwedel, C., Golenhofen, N., Burek, M., Kietz, S., Mankertz, J., Drenckhahn, D. (2005). Occludin as direct target for glucocorticoid-induced improvement of blood-brain barrier properties in a murine in vitro system. J. Physiol. 565: 475-486 [Abstract] [Full Text]
Quick, A. M., Cipolla, M. J. (2005). Pregnancy-induced up-regulation of aquaporin-4 protein in brain and its role in eclampsia. FASEB J. 19: 170-175 [Abstract] [Full Text]
Stair, E. L., Reddy, G., Ritchey, J. W., Saliki, J. T., Qualls, C. W. Jr. (2005). Effects of 1,3,5-Trinitrobenzene on Cytotoxicity and Metabolic Activity of Type I Astrocytes of Rats. International Journal of Toxicology 24: 51-57 [Abstract] [Full Text]
Schaddelee, M. P., Groenendaal, D., DeJongh, J., Cleypool, C. G. J., IJzerman, A. P., De Boer, A. G., Danhof, M. (2004). Population Pharmacokinetic Modeling of Blood-Brain Barrier Transport of Synthetic Adenosine A1 Receptor Agonists. J. Pharmacol. Exp. Ther. 311: 1138-1146 [Abstract] [Full Text]
Zenker, D., Begley, D., Bratzke, H., Rubsamen-Waigmann, H., von Briesen, H. (2003). Human blood-derived macrophages enhance barrier function of cultured primary bovine and human brain capillary endothelial cells. J. Physiol. 551: 1023-1032 [Abstract] [Full Text]
Quadri, S. K., Bhattacharjee, M., Parthasarathi, K., Tanita, T., Bhattacharya, J. (2003). Endothelial Barrier Strengthening by Activation of Focal Adhesion Kinase. J. Biol. Chem. 278: 13342-13349 [Abstract] [Full Text]
Baumgartner, W., Schutz, G. J., Wiegand, J., Golenhofen, N., Drenckhahn, D. (2003). Cadherin function probed by laser tweezer and single molecule fluorescence in vascular endothelial cells. J. Cell Sci. 116: 1001-1011 [Abstract] [Full Text]
Cheng, C. Y., Mruk, D. D. (2002). Cell Junction Dynamics in the Testis: Sertoli-Germ Cell Interactions and Male Contraceptive Development. Physiol. Rev. 82: 825-874 [Abstract] [Full Text]
Adamson, R H, Curry, F E, Adamson, G, Liu, B, Jiang, Y, Aktories, K, Barth, H, Daigeler, A, Golenhofen, N, Ness, W, Drenckhahn, D (2002). Rho and rho kinase modulation of barrier properties: cultured endothelial cells and intact microvessels of rats and mice. J. Physiol. 539: 295-308 [Abstract] [Full Text]
Lecuit, M., Vandormael-Pournin, S., Lefort, J., Huerre, M., Gounon, P., Dupuy, C., Babinet, C., Cossart, P. (2001). A Transgenic Model for Listeriosis: Role of Internalin in Crossing the Intestinal Barrier. Science 292: 1722-1725 [Abstract] [Full Text]
Nico, B, Frigeri, A, Nicchia, G., Quondamatteo, F, Herken, R, Errede, M, Ribatti, D, Svelto, M, Roncali, L (2001). Role of aquaporin-4 water channel in the development and integrity of the blood-brain barrier. J. Cell Sci. 114: 1297-1307 [Abstract]
Wang, W., Dentler, W. L., Borchardt, R. T. (2001). VEGF increases BMEC monolayer permeability by affecting occludin expression and tight junction assembly. Am. J. Physiol. Heart Circ. Physiol. 280: H434-H440 [Abstract] [Full Text]
Fischer, S., Wobben, M., Kleinstuck, J., Renz, D., Schaper, W. (2000). Effect of astroglial cells on hypoxia-induced permeability in PBMEC cells. Am. J. Physiol. Cell Physiol. 279: C935-C944 [Abstract] [Full Text]
Ban, Y., Rizzolo, L. J. (2000). Differential regulation of tight junction permeability during development of the retinal pigment epithelium. Am. J. Physiol. Cell Physiol. 279: C744-C750 [Abstract] [Full Text]
Utsumi, H., Chiba, H., Kamimura, Y., Osanai, M., Igarashi, Y., Tobioka, H., Mori, M., Sawada, N. (2000). Expression of GFRalpha -1, receptor for GDNF, in rat brain capillary during postnatal development of the BBB. Am. J. Physiol. Cell Physiol. 279: C361-C368 [Abstract] [Full Text]
Kanda, T., Yamawaki, M., Iwasaki, T., Mizusawa, H. (2000). Glycosphingolipid antibodies and blood-nerve barrier in autoimmune demyelinative neuropathy. Neurology 54: 1459-1464 [Abstract] [Full Text]
Tran, N. D., Correale, J., Schreiber, S. S., Fisher, M., Chan, P. H. (1999). Transforming Growth Factor-{beta} Mediates Astrocyte-Specific Regulation of Brain Endothelial Anticoagulant Factors � Editorial Comment. Stroke 30: 1671-1678 [Abstract] [Full Text]
Fischer, S., Clauss, M., Wiesnet, M., Renz, D., Schaper, W., Karliczek, G. F. (1999). Hypoxia induces permeability in brain microvessel endothelial cells via VEGF and NO. Am. J. Physiol. Cell Physiol. 276: C812-C820 [Abstract] [Full Text]
Grant, G. A., Abbott, N. J., Janigro, D. (1998). Understanding the Physiology of the Blood-Brain Barrier: In Vitro Models. Physiology 13: 287-293 [Abstract] [Full Text]
Dramsi, S., Levi, S., Triller, A., Cossart, P. (1998). Entry of Listeria monocytogenes into Neurons Occurs by Cell-to-Cell Spread: an In Vitro Study. Infect. Immun. 66: 4461-4468 [Abstract] [Full Text]
Adamson, R. H., Liu, B., Fry, G. N., Rubin, L. L., Curry, F. E. (1998). Microvascular permeability and number of tight junctions are modulated by cAMP. Am. J. Physiol. Heart Circ. Physiol. 274: H1885-H1894 [Abstract] [Full Text]
Sarker, M H, Easton, A S, Fraser, P A (1998). Regulation of cerebral microvascular permeability by histamine in the anaesthetized rat. J. Physiol. 507: 909-918 [Abstract] [Full Text]
Duport, S., Robert, F., Muller, D., Grau, G., Parisi, L., Stoppini, L. (1998). An in vitro blood-brain barrier model: Cocultures between endothelial cells and organotypic brain slice�cultures. Proc. Natl. Acad. Sci. USA 95: 1840-1845 [Abstract] [Full Text]
Thomas, S. A., Abbruscato, T. J., Hruby, V. J., Davis, T. P. (1997). The Entry of [D-Penicillamine2,5]Enkephalin into the Central Nervous System: Saturation Kinetics and Specificity. J. Pharmacol. Exp. Ther. 280: 1235-1240 [Abstract] [Full Text]
Hirase, T, Staddon, J., Saitou, M, Ando-Akatsuka, Y, Itoh, M, Furuse, M, Fujimoto, K, Tsukita, S, Rubin, L. (1997). Occludin as a possible determinant of tight junction permeability in endothelial cells. J. Cell Sci. 110: 1603-1613 [Abstract]
Tran, N. D., Wong, V. L.Y., Schreiber, S. S., Bready, J. V., Fisher, M., Peters, K. (1996). Regulation of Brain Capillary Endothelial Thrombomodulin mRNA Expression. Stroke 27: 2304-2311 [Abstract] [Full Text]
Staddon, J., Herrenknecht, K, Smales, C, Rubin, L. (1995). Evidence that tyrosine phosphorylation may increase tight junction permeability. J. Cell Sci. 108: 609-619 [Abstract]
Wolburg, H, Neuhaus, J, Kniesel, U, Krauss, B, Schmid, E., Ocalan, M, Farrell, C, Risau, W (1994). Modulation of tight junction structure in blood-brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes. J. Cell Sci. 107: 1347-1357 [Abstract]
Rizzolo, L., Li, Z. (1993). Diffusible, retinal factors stimulate the barrier properties of junctional complexes in the retinal pigment epithelium. J. Cell Sci. 106: 859-867 [Abstract]
Fenyves, A., Behrens, J, Spanel-Borowski, K (1993). Cultured microvascular endothelial cells (MVEC) differ in cytoskeleton, expression of cadherins and fibronectin matrix. A study under the influence of interferon-gamma. J. Cell Sci. 106: 879-890 [Abstract]
Scott, P., Bicknell, R (1993). The isolation and culture of microvascular endothelium. J. Cell Sci. 105: 269-273
Schulze, C, Firth, J. (1993). Immunohistochemical localization of adherens junction components in blood-brain barrier microvessels of the rat. J. Cell Sci. 104: 773-782 [Abstract]