Skip to main content

Advertisement

SpringerLink
Log in

In Search of the Astrocytic Factor(s) Modulating Blood–Brain Barrier Functions in Brain Capillary Endothelial Cells In Vitro

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Summary

1. The blood–brain barrier (BBB) is formed by brain capillary endothelial cells (ECs). There are various cell types, in particular astrocytes, but also pericytes and neurons, located in close vicinity to the capillary ECs which may influence formation and function of the BBB. Based on this consideration, this paper discusses various aspects of the influence of the surrounding cells on brain capillary ECs with special focus on the role of astrocytes.

2. Based on the morphology of the BBB, important aspects of brain EC functions are summarized, such as transport functions and maintenance of low paracellular permeability. Moreover, various facets are discussed with respect to the influence of astrocytes, pericytes, microglia, and neurons on the BBB. Data on the role of glial cells in the ontogenesis of the BBB are presented subsequently. The knowledge on this subject is far from being complete, however, these data imply that the neural/neuronal environment rather than glial cells may be of importance in the maturation of the barrier.

3. The role of glial cells in the induction and maintenance of the BBB is discussed under physiological as well as pathological conditions. Although the literature presents manifold evidence for a great variety of effects induced by astroglia, there are also many controversies, which may result from different cellular models and experimental conditions used in the respective studies. Numerous factors secreted by astrocytes have been shown to induce a BBB phenotype. On the molecular level, increased expression of barrier-relevant proteins (e.g., tight junction proteins) is documented in the presence of astrocyte-derived factors, and many studies demonstrate the improvement of physiological parameters, such as increased transendothelial resistance and decreased paracellular permeability, in different in vitro models of the BBB. Moreover, one has to take into account that the interaction of brain ECs and astrocytes is bi-directional, and that the other cell types surrounding the brain microvasculature also contribute to BBB function or dysfunction, respectively.

4. In conclusion, it is expected that the present and future research focused on molecular mechanisms and signaling pathways will produce new and exciting insights into the complex network of BBB regulation: the cornerstone is laid.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abbott, N. J., Hughes, C. C., Revest, P. A., and Greenwood, J. (1992). Development and characterisation of a rat brain capillary endothelial culture: Towards an in vitro blood–brain barrier. J. Cell Sci. 103(Pt 1):23–37.

    PubMed  CAS  Google Scholar 

  • Abbruscato, T. J., and Davis, T. P. (1999). Protein expression of brain endothelial cell E-cadherin after hypoxia/aglycemia: Influence of astrocyte contact. Brain Res. 842:277–286.

    Article  PubMed  CAS  Google Scholar 

  • Abdul-Khaliq, H., Schubert, S., Stoltenburg-Didinger, G., Troitzsch, D., Bottcher, W., Hubler, M., Meissler, M., Grosse-Siestrop, C., Alexi-Meskishvili, V., Hetzer, R., and Lange, P. E. (2000) Protein S-100beta in brain and serum after deep hypothermic circulatory arrest in rabbits: Relationship to perivascular astrocytic swelling. Clin. Chem. Lab. Med. 38:1169–1172.

    Article  PubMed  CAS  Google Scholar 

  • Arthur, F. E., Shivers, R. R., and Bowman, P. D. (1987). Astrocyte-mediated induction of tight junctions in brain capillary endothelium: An efficient in vitro model. Dev. Brain Res. 36:155–159.

    Article  Google Scholar 

  • Balabanov, R., and Dore-Duffy, P. (1998). Role of the CNS microvascular pericyte in the blood–brain barrier. J. Neurosci. Res. 53:637–644.

    Article  PubMed  CAS  Google Scholar 

  • Bauer, H. (1999). Glucose transporters in mammalian brain development. In Pardridge, W. B. (ed.), Introduction to the Blood–Brain Barrier, Cambridge University Press, Cambridge, UK, pp. 175–187.

    Google Scholar 

  • Bauer, H. C., and Bauer, H. (2000). The blood–brain barrier: Still an enigma? Cell. Mol. Neurobiol. 20:13–29.

    Article  PubMed  CAS  Google Scholar 

  • Bauer, H. C., Bauer, H., Lametschwandtner, A., Amberger, A., Ruiz, P., and Steiner, M. (1993). Neovascularization and the appearance of morphological characteristics of the blood–brain barrier in the embryonic mouse central nervous system. Dev. Brain Res. 75:269–278.

    Article  CAS  Google Scholar 

  • Bauer, H., Sonnleitner, U., Lametschwandtner, A., Steiner, M., Adam, H., and Bauer H. C. (1995). Ontogenic expression of the erythroid-type glucose transporter (GLUT1) in the telencephalon of the mouse: Corrrelation to the tightening of the blood–brain barrier. Dev. Brain Res. 86:317–325.

    Article  CAS  Google Scholar 

  • Bauer, H. C., Tontsch, U. Amberger, A., and Bauer, H. (1990). gamma-Glutamyl transpeptidase (GGTP) and Na+, K+-ATPase activities in different subpopulations of cloned cerebral endothelial cells: Response to glial stimulation. Biochem. Biophys. Res. Co. 168:358–363.

    Article  CAS  Google Scholar 

  • Beck, D. W., Vinters, H. V., Hart, M. N., and Cancilla, P. A. (1984). Glial cells influence polarity of the blood–brain barrier. J. Neuropath. Exp. Neurol. 43:219–224.

    Article  PubMed  CAS  Google Scholar 

  • Benistant, C., Dehouck, M. P., Fruchart, J. C., Cecchelli, R., and Lagarde, M. (1995). Fatty acid composition of brain capillary endothelial cells—effect of the coculture with astrocytes. J. Lipid Res. 36:2311–2319.

    PubMed  CAS  Google Scholar 

  • Blasig, I. E., Giese, H., Schroeter, M. L., Sporbert, A., Utepbergenov, D. I., Buchwalow, I. B., Neubert, K., Schönfelder, G., Freyer, D., Schimke, I., Siems, W.-E., Paul, M., Haseloff, R. F., and Blasig, R. (2001). NO and oxy-radical metabolism in new cell lines of rat brain capillary endothelial cells forming the blood–brain barrier. Microvasc. Res. 62:114–127.

    Article  PubMed  CAS  Google Scholar 

  • Bowman, P. D., Betz, A. L., Ar, D., Wolinsky, J. S., Penney, J. B., Shivers, R. R., and Goldstein, G. W. (1981). Primary culture of capillary endothelium from rat-brain. In Vitro Cell. Dev. B 17:353–361.

    Article  CAS  Google Scholar 

  • Brightman, M. W., and Reese, T. S. (1969). Junctions between intimately apposed cell membranes in the vertebrate brain. J. Cell Biol. 40:648–677.

    Article  PubMed  CAS  Google Scholar 

  • Brillault, J., Berezowski, V., Cecchelli, R., and Dehouck, M. P. (2002). Intercommunications between brain capillary endothelial cells and glial cells increase the transcellular permeability of the blood brain barrier during ischaemia. J. Neurochem. 83:807–817

    Article  PubMed  CAS  Google Scholar 

  • Butt, A. M., Jones, H. C., and Abbott, N. J. (1990). Electrical resistance across the blood–brain barrier in anaesthetised rats: A developmental study. J. Physiol.-London 429:47–62.

    PubMed  CAS  Google Scholar 

  • Caley, D. W., and Maxwell, D. S. (1970). Development of the blood and extracellular spaces during postnatal maturation of rat cerebral cortex. J. Comp. Neurol. 138:31–48.

    Article  PubMed  CAS  Google Scholar 

  • Collins, V. P. (2002). Cellular mechanisms targeted during astrocytoma progression. Cancer Lett. 188:1–7.

    Article  PubMed  CAS  Google Scholar 

  • Crone, C., and Olesen, S. P. (1982). Electrical resistance of brain microvascular endothelium. Brain Res. 241:49–55.

    Article  PubMed  CAS  Google Scholar 

  • Davson, H., and Oldendorf, W. H. (1967). Transport in the central nervous system. Proc. R. Soc. Med. 60:326–328.

    PubMed  CAS  Google Scholar 

  • DeBault, L. E., and Cancilla, P. A. (1980). gamma-Glutamyl transpeptidase in isolated brain endothelial cells and induction by glial cells in vitro. Science 207:653–655.

    Article  PubMed  CAS  Google Scholar 

  • Dehouck, M. P., Meresse, S., Delorme, P., Fruchart, J. C., and Cecchelli, R. (1990). An easier, reproducible, and mass-production method to study the blood–brain barrier in vitro. J. Neurochem. 54:1798–1801.

    Article  PubMed  CAS  Google Scholar 

  • Dehouck, M. P., Vigne, P., Torpier, G., Breittmayer, J. P., Cecchelli, R., and Frelin, C. (1997). Endothelin-1 as a mediator of endothelial cell-pericyte interactions in bovine brain capillaries. J. Cerebr. Blood F. Met. 17:464-469.

    Article  CAS  Google Scholar 

  • Dermietzel, R. (1974). Junctions in the central nervous system of the cat. III. Gap junctions and membrane-associated orthogonal particle complexes (MOPC) in astrocytic membranes. Cell Tissue Res. 149:121–135.

    Article  PubMed  CAS  Google Scholar 

  • Dermietzel, R., and Krause, D. (1991). Molecular anatomy of the blood–brain barrier as defined by immunocytochemistry. Int. Rev. Cytol. 12:57–109.

    Article  Google Scholar 

  • Dietrich, W. D., Alonso, O., and Halley M. (1994). Early microvascular and neuronal consequences of traumatic brain injury: A light and electron microscopic study in rats. J. Neurotraum. 11:289-301.

    Article  CAS  Google Scholar 

  • ElHafny, B., Bourre, J. M., and Roux, F. (1996). Synergistic stimulation of gamma-glutamyl transpeptidase and alkaline phosphatase activities by retinoic acid and astroglial factors in immortalized rat brain microvessel endothelial cells. J. Cell Physiol. 167:451–468.

    Article  CAS  Google Scholar 

  • Estrada, C., Bready, J. V., Berliner, J. A., Pardridge, W. M., and Cancilla, P. A. (1990). Astrocyte growth stimulation by a soluble factor produced by cerebral endothelial cells in vitro. J. Neuropath. Exp. Neurol. 49:539–549.

    Article  PubMed  CAS  Google Scholar 

  • Fidler, I. J., Yano, S., Zhang, R. D., Fujimaki, T., and Bucana, C. D. (2002). The seed and soil hypothesis: Vascularisation and brain metastasis. Lancet Oncol. 3:53–57.

    Article  PubMed  CAS  Google Scholar 

  • Fischer, S., Wobben, M., Kleinstuck, J., Renz, D., and Schaper, W. (2000). Effect of astroglial cells on hypoxia-induced permeability in PBMEC cells. Am. J. Physiol.-Cell Physiol. 279:C935–C944.

    PubMed  CAS  Google Scholar 

  • Gaillard, P. J., van der Sandt, J. C., Voorwinden, L. H., Vu, D., Nielsen, J. L., de Boer, A. G., and Breimer, D. D. (2000). Astrocytes increase the functional expression of P-glycoprotein in an in vitro model of the blood–brain barrier. Pharm. Res. 17:1198–1205.

    Article  PubMed  CAS  Google Scholar 

  • Garberg, P. (1998). In vitro models of the blood–brain barrier. ATLA-Altern. Lab. Anim. 26:821–847.

    Google Scholar 

  • Giese, H., Mertsch, K., and Blasig, I. E. (1995). Effect of MK-801 and U83836E on a porcine brain capillary endothelial cell barrier during hypoxia. Neurosci. Lett. 191:169–172.

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Mariscal, L., Betanzos, A., Nava, P., and Jaramillo, B. E. (2003). Tight junction proteins. Prog. Biophys. Mol. Bio. 81:1–44.

    Article  CAS  Google Scholar 

  • Gotow, T., and Hashimoto, P. H. (1984). Plasma-membrane organization of astrocytes in elasmobranchs with special reference to the brain barrier system. J. Neurocytol. 13:727–742.

    Article  PubMed  CAS  Google Scholar 

  • Greenwood, J. (1991). Astrocytes, cerebral endothelium, and cell culture. The pursuit of an in vitro blood–brain barrier. Ann. NY Acad. Sci. 633:424–431.

    Article  Google Scholar 

  • Habgood, M. D., Sedgwick, J. E. C., Dziegielewska, K. M., and Saunders, N. R. (1992). A developmentally regulated blood–cerebrospinal fluid barrier exchange during postnatal brain development in the rat. J. Physiol.-London 468:73–83.

    Google Scholar 

  • Hayashi, Y., Nomura, M., Yamagishi, S., Harada, S., Yamashita, J., and Yamamoto, H. (1997). Induction of various blood–brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes. Glia 19:13-26.

    Article  PubMed  CAS  Google Scholar 

  • Hirano, A., Kawanami T., and Llena J. F. (1994). Electron-microscopy of the blood–brain-barrier in disease. Microsc. Res. Techniq. 27:543–556.

    Article  CAS  Google Scholar 

  • Holash, J. A., Noden, D. M., and Stewart, P. A. (1993). Re-evaluation the role of astrocytes in blood–brain barrier induction. Dev. Dynam. 197:14–25.

    CAS  Google Scholar 

  • Igarashi, Y., Utsumi, H., Chiba, H., Yamada-Sasamori, Y., Tobioka, H., Kamimura, Y., Furuuchi, K., Kokai, Y., Nakagawa, T., Mori, M., and Sawada, N. (1999). Glial cell line-derived neurotrophic factor induces barrier function of endothelial cells forming the blood–brain barrier. Biochem. Biophys. Res. Co. 261:108–112.

    Article  CAS  Google Scholar 

  • Kastin, A. J., Akerstrom, V., and Pan, W. H. (2003). Glial cell line-derived neurotrophic factor does not enter normal mouse brain. Neurosci. Lett. 348:239–241.

    Article  Google Scholar 

  • Kramer, S. D., Schutz, Y. B., Wunderli-Allenspach, H., Abbott, N. J., and Begley, D. J. (2002). Lipids in blood–brain barrier models in vitro II: Influence of glial cells on lipid classes and lipid fatty acids. In Vitro Cell. Dev.-An. 38:566–571.

    Article  Google Scholar 

  • Krum, J. M. (1996). Effect of astroglial degeneration on neonatal blood–brain barrier marker expression. Exp. Neurol. 142:29–35.

    Article  PubMed  CAS  Google Scholar 

  • Krum, J. M., and Rosenstein, J. M. (1999). Transient coexpression of nestin, GFAP, and vascular endothelial growth factor in mature reactive astroglia following neural grafting or brain wounds. Exp. Neurol. 160:348–360.

    Article  PubMed  CAS  Google Scholar 

  • Kumagai, A. K. (1999). Glucose transport in brain and retina: Implications in the management and complications of diabetes. Diabetes-Metab. Res. 15:261–273.

    Article  CAS  Google Scholar 

  • Lee, S. W., Kim, W. J., Choi, Y. K., Song, H. S., Son, M. J., Gelman, I. H., Kim, Y. J., and Kim, K. W. (2003). SSeCKS regulates angiogenesis and tight junction formation in blood–brain barrier. Nat. Med. 9:900–906

    Article  PubMed  CAS  Google Scholar 

  • Liebner, S., Fischmann, A., Rascher, G., Duffner, F., Grote, E. H., Kalbacher, H., and Wolburg, H. (2000). Claudin-1 and claudin-5 expression and tight junction morphology are altered in blood vessels of human glioblastoma multiforme. Acta Neuropathol. 100:323–331.

    Article  PubMed  CAS  Google Scholar 

  • Mark, K. S., and Davis, T. P. (2002). Cerebral microvascular changes in permeability and tight junctions induced by hypoxia-reoxygenation. Am. J. Physiol.-Heart C. 282:H1485–1494.

    CAS  Google Scholar 

  • Machein, M. R, Kullmer, J., Fiebich, B. L., Plate, K. H., and Warnke, P. C. (1999). Vascular endothelial growth factor expression, vascular volume, and capillary permeability in human brain tumors. Neurosurgery 44:732–740.

    Article  PubMed  CAS  Google Scholar 

  • Maher, F., Vannucci, S. J., and Simpson, I. A. (1993). Glucose transporter proteins in brain. FASEB J. 8:1003–1011.

    Google Scholar 

  • Maxwell, K., Berliner, J. A., and Cancilla P. A. (1987). Induction of gamma-glutamyl transpeptidase in cultured endothelial cells by a product released by astrocytes. Brain Res. 410:309–314.

    Article  PubMed  CAS  Google Scholar 

  • Mertsch, K., Haseloff, R. F., and Blasig, I. E. (1997). Investigations of radical scavengers by using an in vitro model of blood–brain barrier. In van Zutphen, L. F. M., and Balls, M. (eds.), Animal Alternatives, Welfare and Ethics, Elsevier, Amsterdam, The Netherlands, pp. 881–886.

    Google Scholar 

  • Mertsch, K., Haseloff, R. F., Schroeter, M. L., and Blasig, I. E. (1999). In vitro models of the blood–brain barrier for the investigation of cerebroprotective agents. In Carter A. J., and Kettenmann H. (eds.), Practical Handbook of Methods, Forschungszentrum Jülich, Jülich, Germany, pp. 99–124.

    Google Scholar 

  • Meyer, J., Rauh, J., and Galla, H.-J. (1991). The susceptibility of cerebral endothelial cells to astroglial induction of blood–brain barrier enzymes depends on their proliferative state. J. Neurochem. 57:1971–1977.

    Article  PubMed  CAS  Google Scholar 

  • Mi, H. Y., Haeberle, H., and Barres, B. A. (2001). Induction of astrocyte differentiation by endothelial cells. J. Neurosci. 21:1538–1547.

    PubMed  CAS  Google Scholar 

  • Mischeck, U., Meyer, J., and Galla, H. J. (1989). Characterization of gamma-glutamyl transpeptidase activity of cultured endothelial cells from porcine brain capillaries. Cell Tissue Res. 256:221–226.

    Article  PubMed  CAS  Google Scholar 

  • Nehls, V., and Drenckhahn, D. (1991). Heterogeneity of microvascular pericytes for smooth muscle type alpha-actin. J. Cell Biol. 113:147–154.

    Article  PubMed  CAS  Google Scholar 

  • Papadopoulos, M. C., Saadoun, S., Davies, D. C., and Bell, B. A. (2001a). Emerging molecular mechanisms of brain tumour oedema. Brit. J. Neurosurg. 15:101–108.

    Article  CAS  Google Scholar 

  • Papadopoulos, M. C., Saadon, S., Woodrow, C. J., Davies, D. C., Costa-Martins, P., Moss, R. F., Krishan, S., and Bell, B. A. (2001b). Occludin expression in microvessels of neoplastic and non-neoplastic human brain. Neuropath. Appl. Neuro. 27:384–395.

    Article  CAS  Google Scholar 

  • Papandrikopoulou, A., Frei, A., and Grasser, M. G. (1989). Cloning and expression of gamma-glutamyltranspeptidase from isolated porcine brain capillaries. Eur. J. Biochem. 183:693–698.

    Article  PubMed  CAS  Google Scholar 

  • Pardridge, W. M. (1999). Blood–brain barrier biology and methodology. J. Neurovirol. 5:556–569.

    Article  PubMed  CAS  Google Scholar 

  • Pardridge, W. M., Triguero, D., Yang, J., and Cancilla, P. A. (1990). Comparison of in vitro and in vivo models of drug transcytosis through the blood–brain barrier. J. Pharmacol. Exp. Ther. 253:884–891.

    PubMed  CAS  Google Scholar 

  • Persidsky, Y., Ghorpade, A., Rasmussen, J., Limoges, J., Liu, X. J., Stins, M., Fiala, M., Way, D., Kim, K. S., Witte, M. H., Weinand, M., Carhart, L., and Gendelman, H. E. (1999). Microglial and astrocyte chemokines regulate monocyte migration through the blood–brain barrier in human immnodeficiency virus-1 encephalitis. Am. J. Pathol. 15:1599–1611.

    Google Scholar 

  • Plateel, M., Teisier, E., and Cecchelli, R. (1997). Hypoxia dramatically increases the nonspecific transport of blood–borne proteins to the brain. J. Neurochem. 68:874–877.

    Article  PubMed  CAS  Google Scholar 

  • Proescholdt, M. A., Merill, M. J., Ikejiri, B., Walbridge, S., Akbasak, A., Jacobson, S., and Oldfield, E. H. (2001). Site-specific immune response to implanted gliomas. J. Neurosurg. 95:1012–1019.

    Article  PubMed  CAS  Google Scholar 

  • Ramsauer, M., Krause, D., and Dermietzel, R. (2002) Angiogenesis of the blood–brain barrier in vitro and the function of cerebral pericytes. FASEB J. 16:1274–1276.

    PubMed  CAS  Google Scholar 

  • Rascher, G., Fischmann, A., Krüger, S., Duffner, F., Grote, E.-H., and Wolburg, H. (2002). Extracellular matrix and the blood–brain barrier in glioblastoma multiforme: Spatial segregation of tenascin and agrin. Acta Neuropathol. 104:85–91.

    Article  PubMed  CAS  Google Scholar 

  • Reese, T. S., and Karnovsky, M. J. (1967). Fine structural localization of a blood brain barrier to exogenous peroxidase. J. Cell Biol. 34:207–217.

    Article  PubMed  CAS  Google Scholar 

  • Reuss, B., Dono, R., and Unsicker, K. (2003). Functions of fibroblast growth factor (FGF)-2 and FGF-5 in astroglial differentiation and blood–brain barrier permeability: Evidence from mouse mutants. J. Neurosci. 23:6404–6412.

    PubMed  CAS  Google Scholar 

  • Richards, L. J., Kilpatrick, T. J., Dutton, R., Tan, S. S., Gearing, D. P., Bartlett, P. F., and Murphy, M. (1996). Leukaemia inhibitory factor or related factors promote the differentiation of neuronal and astrocytic precursors within the developing murine spinal cord. Eur. J. Neurosci. 8:291–299.

    Article  PubMed  CAS  Google Scholar 

  • Risau, W. (1991). Induction of blood–brain barrier endothelial cell differentiation. Ann. NY Acad. Sci. 633:405–419.

    Article  PubMed  CAS  Google Scholar 

  • Risau, W. (1997). Mechanisms of angiogenesis. Nature 386:671–674.

    Article  PubMed  CAS  Google Scholar 

  • Risau, W., Hallmann, R., and Albrecht, U. (1986a). Differentiation-dependent expression of proteins in brain endothelium during development of the blood–brain barrier. Dev. Biol. 117:537–545.

    Article  CAS  Google Scholar 

  • Risau, W., Hallmann, R. Albrecht, U., and Henke-Fahle, S. (1986b). Brain induces the expression of an early cell surface marker for blood–brain barrier-specific endothelium. EMBO J. 5:3179–3183.

    CAS  Google Scholar 

  • Roncali, L., Nico, B., Ribatti, D., Bertassi, M., and Mancini, L. (1986). Microscopical and ultrastructural investigation of the development of blood–brain barrier in the chick embryo optic tectum. Acta Neuropathol. 70:193–201.

    Article  PubMed  CAS  Google Scholar 

  • Roux, F., Durieu-Trautmann, O., Chaverot, N., Claire, M., Mailly, P., Bourre, J. M., Strosberg, A. D., and Couraud, P. O. (1994). Regulation of gamma-glutamyl-transpeptidase and alkaline-phosphatase activities in immortalized rat-brain microvessel endothelial-cells. J. Cell Physiol. 159:101–113.

    Article  PubMed  CAS  Google Scholar 

  • Rubin, L. L., Hall, E., Porter, S., Barbu, K., Cannon, C., Horner, H. C., Janatpour, M., Liaw, C. W., Manning, K., Morales, J., Tanner, L. I. Tomaselli, K. J., and Bard, F. (1991). A cell culture model of the blood–brain barrier. J. Cell Biol. 115:1725–1735.

    Article  PubMed  CAS  Google Scholar 

  • Rubin, L. L., and Staddon, J. M. (1999). The cell biology of the blood–brain barrier. Annu. Rev. Neurosci. 22:11–28.

    Article  PubMed  CAS  Google Scholar 

  • Saunders, N. R., Knott, G. W., and Dziegielewska, K. M. (2000). Barriers in the immature brain. Cell. Mol. Neurobiol. 20:29–41.

    Article  PubMed  CAS  Google Scholar 

  • Schroeter, M. L., Mertsch, K., Giese, H., Müller, S., Sporbert, A., Hickel, B., and Blasig, I. E. (1999). Astrocytes enhance radical defence in capillary endothelial cells constituting the blood–brain barrier. FEBS Lett. 449:241–244.

    Article  PubMed  CAS  Google Scholar 

  • Schroeter, M. L., Müller, S., Lindenau, J., Wiesner, B., Hanisch, U. K., Wolf, G., and Blasig, I. E. (2001). Astrocytes induce manganese superoxide dismutase in brain capillary endothelial cells. NeuroReport 8:2513–2517.

    Article  Google Scholar 

  • Stanness, K. A., Guatteo, E., and Janigro D. (1996). A dynamic model of the blood–brain barrier “in vitro.” Neurotoxicology 17:481–496.

    PubMed  CAS  Google Scholar 

  • Stevenson, B. R., and Keon, B. H. (1998). The tight junction: Morphology to molecules. Annu. Rev. Cell Dev. Bi. 14:89–109.

    Article  CAS  Google Scholar 

  • Stewart, P. A., and Hayakawa, K. (1994). Early structural changes in blood–brain barrier vessels of the rat embryo. Dev. Brain Res. 78:25–34.

    Article  CAS  Google Scholar 

  • Stewart, P. A., and Wiley, M. J. (1981). Developing nervous tissue induces formation of the blood–barrier characteristics in invading endothelial cells: A study using Quail-chick transplantation chimeras. Dev. Biol. 84:183–192.

    Article  PubMed  CAS  Google Scholar 

  • Tao-Cheng, J.-H., Nagy, Z., and Brightman, M. W. (1987). Tight junctions of brain endothelium in vitro are enhanced by astroglia. J. Neurosci. 7:3293–3299.

    PubMed  CAS  Google Scholar 

  • Tao-Cheng, J.-H., Nagy, Z., and Brightman, M. W. (1990). Astrocytic orthogonal arrays in intramembranous particle assemblies modulated by brain endothelial cells in vitro. J. Neurocytol. 19:143–153.

    Article  PubMed  CAS  Google Scholar 

  • Tontsch, U., and Bauer, H. C. (1991). Glial cells and neurons induce blood–brain barrier related enzymes in cultured cerebral endothelial cells. Brain Res. 539:247–253.

    Article  PubMed  CAS  Google Scholar 

  • Tran, N. D., Correale, J., Schreiber, S. S., and Fisher, M. (1999). Transforming growth factor-beta mediates astrocyte-specific regulation of brain endothelial anticoagulant factors. Stroke 30:1671–1677.

    PubMed  CAS  Google Scholar 

  • Tsukita, S., Furuse, M., and Itoh, M. (1999). Structural and signalling molecules come together at tight junctions. Curr. Opin. Cell Biol. 11:628-633.

    Article  PubMed  CAS  Google Scholar 

  • van Deurs, B. (1979). Structural aspects of brain barriers, with special reference to the permeability of the cerebral endothelium and choroidal epithelium. Int. Cytol. 65:117–191.

    Article  Google Scholar 

  • Wiranowska, M., Gonzalvo, A. A., Saporta, S., Gonzalez, O. R., and Prockop. L. D. (1992). Evaluation of blood–brain barrier permeability and the effect of interferon in mouse glioma model. J. Neurooncol. 14:225–236.

    Article  PubMed  CAS  Google Scholar 

  • Wolburg, H. (1995). Orthogonal arrays of intramembranous particles: A review with special reference to astrocytes. J. Hirnforsch. 36:239–258.

    PubMed  CAS  Google Scholar 

  • Xu, J., and Ling, E. A. (1994). Studies of the ultrastructure and permeability of the blood–brain barrier in the developing corpus callosum in postnatal rat brain using electron dense tracers. J. Anat. 84:227–237.

    Google Scholar 

  • Yoshida, Y., Yamada, M., Wakabayashi, K., and Ikuta, F. (1988). Endothelial fenestrae in the rat fetal cerebrum. Dev. Brain Res. 44:211–219.

    Article  CAS  Google Scholar 

  • Zhang, W. D., Smith, C., Shapiro, A., Monette, R., Hutchison, J., and Stanimirovic, D. (1999). Increased expression of bioactive chemokines in human cerebromicrovascular endothelial cells and astrocytes subjected to simulated ischemia in vitro. J. Neuroimmunol. 101:148–160.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Forschungsinstitut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, D-13125, Berlin, Germany

    R. F. Haseloff & I. E. Blasig

  2. Universität Salzburg, Fachbereich Organismische Biologie, A-5020, Salzburg, Austria

    H. -C. Bauer & H. Bauer

Authors
  1. R. F. Haseloff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. E. Blasig
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. -C. Bauer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Bauer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. F. Haseloff.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Haseloff, R.F., Blasig, I.E., Bauer, H.C. et al. In Search of the Astrocytic Factor(s) Modulating Blood–Brain Barrier Functions in Brain Capillary Endothelial Cells In Vitro. Cell Mol Neurobiol 25, 25–39 (2005). https://doi.org/10.1007/s10571-004-1375-x

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-004-1375-x

Key words

Search

Navigation