Recent Advances in the Development of Cell Culture Models for the Blood-Brain- and Blood-CSF-Barrier

  • Thorsten Nitz
  • Tanja Eisenblätter
  • Matthias Haselbach
  • Hans-Joachim Galla


Two cellular barriers effectively protect the mammalian brain from passive entrance of ions and hydrophilic compounds circulating in the bloodstream. First, the vascular capillaries of the brain are almost entirely lined by unique endothelial cells that build up the blood-brain barrier (BBB). In those very limited regions of the brain, where the endothelial cells do not provide a sufficiently tight barrier — namely in certain parts of the ventricular system, the choroid plexus — an underlying sheet of epithelial cells serves to separate blood from cerebrospinal fluid and thereby forms the blood-cerebrospinal fluid barrier (BCFB). The ability of both cell types to separate two compartments of different chemical composition arises from the formation of very tight intercellular junctions (tight junctions). These cell-cell contacts prevent diffusive permeation of blood derived compounds along the intercellular cleft between adjacent cells into the CNS or vice versa.


Vascular Endothelium Growth Factor Tight Junction Barrier Property Choroid Plexus Lysophosphatidic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Brindley, D.N. and Waggoner, D.W., 1998, Mammalian lipid phosphohydrolases. J. Biol. Chem. 273: 1–4.CrossRefGoogle Scholar
  2. Chang, C., Wang, X., Caldwell, R.B., 1997, Serum opens tight junctions and reduces ZO-1 protein in retinal epithelial cells. J. Neurochem. 69: 859–867.PubMedCrossRefGoogle Scholar
  3. Crook, R.B., Kasagami, H., Prusinger, S.B., 1981, Culture and characterisation of epithelial cell from bovine choroid plexus. J.Neurochem 37: 845–854.PubMedCrossRefGoogle Scholar
  4. El-Shabrawi, Y., Eckhardt, M., Berghold, A., Faulborn, J., Auboeck, L., Mangge, H. and Ardjomand, N., 2000, Synthesis pattern of matrix metalloproteinases (MMPs) and inhibitors (TIMPs) in human expiant organ cultures after treatment with latanoprost and dexamethasone. Eye 3a: 375–383.CrossRefGoogle Scholar
  5. English, D., Kovala, A.T., Welch, Z., Harvey, K.A., Siddiqui, R.A., Brindley, D.N. and Garcia J.G.N., 1999, Induction of Endothelial Cell Chemotaxis by Sphingosine 1-Phosphate and Stabilization of Endothelial Monolayer Barrier Function by Lysophosphatidic Acid, Potential Mediators of Hematopoietic Angiogenesis. J. Hematother. Stem Cell Res. 8: 627–634.PubMedCrossRefGoogle Scholar
  6. English, D., Cui, Y., Siddiqui, R., Patterson, C., Natarajan, V., Brindley D.N. and Garcia, J.G.N., 1999, Induction of endothelial monolayer permeability by phosphatidate. J. Cell. Biochem. 75: 105–117.PubMedCrossRefGoogle Scholar
  7. Forth, W., Henschler, D. and Rummel, W., 1987, Allgemeine und spezielle Pharmakologie und Toxikologie. B.I. Wissenschaftsverlag, Mannheim/Wien/Zürich.Google Scholar
  8. Gaits, F., Fourcade, O., Le Balle, F., Gueguen, G., Gaige, B., Gassama-Diagne, A., Fauch, J., Salles, J.B., Mauco, G., Simon, M.F. and Chap, H., 1997, Lysophosphatidic acid as a phospholipid mediator: pathways of synthesis. FEBS Lett. 410: 54–58.PubMedCrossRefGoogle Scholar
  9. Gath, U., Hakvoort, A., Wegener, J., Decker, S., Galla, H.J., 1997, Porcine choroid plexus cells in culture: expression of polarised phenotype, maintenance of barrier properties and apical secretion of CSF-components. Eur. J. Cell Biol. 74: 68–78.PubMedGoogle Scholar
  10. Goetzl, E.J., Lee, H., Toshifumi, A., Stossel, T.P., Turck, C.W. and Karliner, J.S., 2000, Gelsolin Binding and Cellular Presentation of Lysophosphatidic Acid. J. Biol. Chem. 19: 14573–14578.CrossRefGoogle Scholar
  11. Hakvoort, A., Haselbach, M., Wegener, J., Hoheisel, D., Galla, H.J., 1998, The polarity of choroid plexus epithelial cells in vitro is improved in serum-free medium. J. Neurochem. 71: 1141–1150.PubMedCrossRefGoogle Scholar
  12. Haselbach, M., Wegener, J., Decker, S., Engelbertz, C, Galla, H.J., 2001, Choroid plexus epithelial cells in culture: Regulation of barrier properties and transport processes. Micr. Res. Tech., in press.Google Scholar
  13. Hoheisel, D., Nitz, T., Franke, H., Wegener, J. and Galla, H.-J., 1998, Hydrocortisone reinforces the blood-brain barrier properties in a serum free cell culture system. Biochem. Biophys. Res. Commun. 244: 312–316.PubMedCrossRefGoogle Scholar
  14. Korte, D., 2000, PHD-Thesis Universität Münster, Germany.Google Scholar
  15. Kroll, J. and Waltenberger, J., 2000, Regulation of endothelial function and angiogenesis by vascular endothelial growth factor-A (VEGF-A). Z. Kardiol. 89: 206–218.PubMedCrossRefGoogle Scholar
  16. Meßmer, U.K., Winkel, G., Briner, V.A. and Pfeilschifter, J., 2000, Suppression of apoptosis by glucocorticoids in glomerular endothelial cells: effects on proapoptotic pathways. Br. J. Pharmacol. 129: 1673–1683.PubMedCrossRefGoogle Scholar
  17. Neufeld, G., Cohen, T., Gengrinovitch, S. and Poltorak, Z., 1999, Vascular endothelial growth factor (VEGF) and its receptor. FASEB J. 13: 9–22.PubMedGoogle Scholar
  18. Panetti, T.S., Chen, H., Misenheimer, T.M., Getzler, S.B. and Mosher D.F., 1997, Endothelial cell mitogenesis induced by LPA: inhibition by thrombospondin-1 and thrombospondin-2. J. Lab. Clin. Med. 129: 208–216.PubMedCrossRefGoogle Scholar
  19. Parmelee, J.T., Johanson, C.E., 1989, Development of potassium transport capability by choroid plexus of infant rats. Am. J. Physiol. 256: R786–R791.PubMedGoogle Scholar
  20. Ramanthan, V.K., Chung, S.J., Giacomini, K.M., Brett, CM., 1997, Taurine transport in cultured choroid plexus. Pharma Res 14: 406–409.CrossRefGoogle Scholar
  21. Risau, W., 1997, Mechanisms of angiogenesis. Nature 386: 671–674.PubMedCrossRefGoogle Scholar
  22. Schulze, C., Smales, C., Rubin, L.L. and Staddon, M.J., 1997, Lysophosphatidic Acid Increases Tight Junction Permeability in Cultured Brain Endothelial Cells. J. Neurochem. 68: 991–1000.PubMedCrossRefGoogle Scholar
  23. Simmons, C., 1992, The development of cellular polarity in transport epithelial. Sem Perinatol 16: 78–89.Google Scholar
  24. Singer, K.L., Stevenson, B.R., Woo, P.L. and Firestone, G.L., 1994, Relationship of Serine/Threonine Phosphorylation/Dephosphorylation Signaling to Glucocorticoid Regulation of Tight Junction Permeability and ZO-1-Distribution in Nontransformen Mammary Epithelial Cells. J. Biol. Chem. 269: 16108–16115.PubMedGoogle Scholar
  25. Southwell, B.R., Duan, W., Alcorn, D., Brack, C., Richardson, S.J., Köhrle, J., Schreiber, G., 1993, Thyroxine transport to the brain: role of protein synthesis by the choroid plexus. Endocrinology 133: 2116–2126.PubMedCrossRefGoogle Scholar
  26. Tewes, B., Franke, H., Hellwig, S., Hoheisel, D., Decker, S., Griesche, D., Tilling, T., Wegener, J. and Galla, H.-J., 1997, Preparation of endothelial cells in primary cultures obtained from the brains of 6-month-old pigs. In Transport Across the Blood-Brain Barrier: In Vitro and In Vivo Techniques (A.G. de Boer and W. Sutanto, eds.), Academic Publishers, Amsterdam: Harwood, pp. 91–97.Google Scholar
  27. Tokumura, A., Iimori, M., Nishioka, Y., Kitahara, M., Sakashita, M. and Tanaka, S., 1994, Lysophosphatidic acids induce proliferation of cultured vascular smooth muscle cells from rat aorta. Am. J. Physiol. 267: C204–C210.PubMedGoogle Scholar
  28. Van Meer, G., Simons, K., 1986, The function of tight junction in maintaining differences in lipid composition between the apical and basolateral cell surface domains of MDCK cell. EMBO J. 5, 1455–1464.PubMedGoogle Scholar
  29. Wegener, J. and Galla, H.-J., 1996, The role of non-lamellar lipid structures in the formation of tight junctions. Chem. Phys. Lipids 81: 229–255.CrossRefGoogle Scholar
  30. Zeuthen, T., Wright, E.M., 1981, Epithelial potassium transport: tracer and electrophysiological studies in choroid plexus. J. Membr. Biol. 60: 105–128.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Thorsten Nitz
    • 1
  • Tanja Eisenblätter
    • 1
  • Matthias Haselbach
    • 1
  • Hans-Joachim Galla
    • 1
  1. 1.Institut für Biochemie, Westfälische Wilhelms-Universität MünsterMünsterGermany

Personalised recommendations