Skip to main content
SpringerLink
Log in

Dynamics of CNS Barriers: Evolution, Differentiation, and Modulation

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

Summary

1. Three main barrier layers at the interface between blood and tissue protect the central nervous system (CNS): the endothelium of brain capillaries, and the epithelia of the choroid plexus (CP) and the arachnoid. The classical work on these barriers in situ until the 1970s laid the foundations for modern understanding. Techniques for brain endothelial cell isolation and culture pioneered by Ferenc Joó in the 1970s opened up new fields of examination, enabling study of mechanisms at the cellular and molecular level.

2. Astrocytic glial cells are closely associated with the brain endothelial barrier. During evolution the barrier appears to have shifted from the glial to the endothelial layer, in parallel with the increasing importance of the microvasculature and its regulation. Vestiges of the barrier potential of glia remain in the modern mammalian CNS.

3. Evolutionary evidence suggests that the advantage derived from ionic homeostasis around central synapses was the major selective pressure leading to refinement of CNS barrier systems. This is one element of the modern multitasking’ barrier function.

4. While epithelia are constitutively able to form barriers at appropriate interfaces, the ‘default’ condition for endothelia is more leaky; inductive influences from associated cells especially astrocytes are important in generating the full blood–brain barrier (BBB) phenotype in brain capillaries. The underlying mechanisms are being elucidated at the molecular and genomics level.

5. The barrier layers of the nervous system can be modulated by a number of receptor-mediated processes, involving several signal transduction pathways, both calcium dependent and independent. Some agents acting as ‘inducers’ in the long term can act as ‘modulators’ in the short-term, with some overlap of signaling pathways. Modulating agents may be derived both from the blood and from cells associated with cerebral vessels. Less is known about the modulation of the CP.

6. The challenge for the next era of CNS barrier studies will be to apply new knowledge from proteomics and genomics to understanding the in vivo condition in physiology and pathology.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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. (1992). Comparative physiology of the blood–brain barrier. In Bradbury, M. W. B. (ed.), Physiology and Pharmacology of the Blood–Brain Barrier, Springer-Verlag, Heidelberg, pp. 371–396.

    Google Scholar 

  • Abbott, N. J. (1998). Role of intracellular calcium in regulation of brain endothelial permeability. In Pardridge W. M. (ed.) Introduction to the Blood–Brain Barrier: Methodology and Biology, Cambridge University Press, Cambridge, UK, pp. 345–353.

    Google Scholar 

  • Abbott, N. J. (2000). Inflammatory mediators and modulation of blood–brain barrier permeability. Cell. Molec. Neurobiol. 20:31–147.

    Google Scholar 

  • Abbott, N. J. (2002). Astrocyte–endothelial interactions and blood–brain barrier permeability. J. Anat. 200:629–638.

    PubMed  CAS  Google Scholar 

  • Abbott, N. J., and Revest, P. A. (1991). Control of brain endothelial permeability. Cerebrovasc. Brain Metab. Rev. 3:39–72.

    PubMed  CAS  Google Scholar 

  • Abbott, N. J., and Romero, I. A. (1996). Transporting therapeutics across the blood–brain barrier. Molec. Med. Today 2:106–113.

    CAS  Google Scholar 

  • Abbott, N. J., and Romero, I. A. (1999). Patterns of toxic damage to brain endothelium in relation to cell metabolism. In Paulson, O., Moos Knudsen, G., and Moos, T. (eds.), Brain Barrier Systems, Alfred Benzon Symposium No 45, Munksgaard, Copenhagen, pp. 269–279.

    Google Scholar 

  • Abbott, N. J., Bundgaard, M., and Cserr, H. F. (1986a). Comparative physiology of the blood–brain barrier. In Suckling, A. J., Rumsby, M. G., and Bradbury, M. W. (eds.) The Blood–Brain Barrier in Health and Disease, Ellis Horwood, Chichester, UK, pp. 52–72.

    Google Scholar 

  • Abbott, N. J., Lane, N. J., and Bundgaard, M. (1986b). The blood–brain interface in invertebrates. Ann. NY Acad. Sci. 481:20–41.

    CAS  Google Scholar 

  • Abbott, N. J., Mendonca, L. L. F., and Dolman, D. E. M. (2003). The blood–brain barrier in systemic lupus erythematosus. Lupus. 12:908–915.

    PubMed  CAS  Google Scholar 

  • Abbott, N. J., Revest, P. A., and Romero, I. A. (1992). Astrocyte–endothelial interaction: Physiology and pathology. Neuropath. Appl. Neurobiol. 18:424–433.

    Article  CAS  Google Scholar 

  • Abbott, N. J., Mitchell, G., Ward, K. J., Abdullah, F., and Smith, I. C. H. (1997). An electrophysiological method for measuring the potassium permeability of the nerve perineurium. Brain Res. 776:204–213.

    PubMed  CAS  Google Scholar 

  • Abbott, N. J., Zlokovic, B. V., Taylor, M., Hart, J., and Rogac, L. (1988). Amino acid transport by a glial blood–brain barrier: Studies in an elasmobranch fish. In Rakic, L., Begley, D. J., Davson, H., and Zlokovic B. V. (eds.), Peptide and Amino Acid Transport Mechanisms in the Central Nervous System, Macmillan Press and Serbian Academy of Sciences and Arts, London and Belgrade, pp. 241–244.

    Google Scholar 

  • Ábrahám, C. S., Deli, M. A., Joó, F., Megyeri, P., and Torpier, G. (1996). Intracarotid tumour necrosis factor-α administration increases the blood–brain barrier permeability in the cerebral cortex of newborn pig: Quantitative aspects of double labelling studies and confocal laser scanning analysis. Neurosci. Lett. 208:85–88.

    PubMed  Google Scholar 

  • Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., and Walter, P. (2002). Molecular Biology of the Cell, 4th edn., Garland Science, New York.

    Google Scholar 

  • Allt, G., and Lawrenson, J. G. (1997). Is the pial microvessel a good model for blood–brain barrier studies? Brain Res. Rev. 24:67–76.

    PubMed  CAS  Google Scholar 

  • Allt, G., and Lawrenson, J. G. (2000). The blood–nerve barrier: Enzymes, transporters and receptors—a comparison with the blood–brain barrier. Brain Res. Bull. 52:1–12.

    PubMed  CAS  Google Scholar 

  • Allt, G., and Lawrenson, J. G. (2001). Pericytes: Cell biology and pathology. Cells Tissue Organs 169:1–11.

    CAS  Google Scholar 

  • Amédée, T., Robert, A., and Coles, J. A. (1997). Potassium homeostasis and glial energy metabolism. Glia 21:46–55.

    PubMed  Google Scholar 

  • Arlotta, P., Magavi, S. S., and Macklis, J. D. (2003). Molecular manipulation of neural precursors in situ: Induction of adult cortical neurogenesis. Exp. Gerontol. 38:173–182.

    PubMed  CAS  Google Scholar 

  • Arsenijevic, D., Girardier, L., Seydoux, J., Pechere, J. C., Garcia, I., Lucas, R., Change, H. R., and Dulloo, A. G. (1998). Metabolic–cytokine responses to a second immunological challenge with LPS in mice with T. gondii infection. Am. J. Physiol. 274: E439–E445.

    PubMed  CAS  Google Scholar 

  • Balda, M. S., Flores-Maldonado, C., Cereijido, M., and Matter, K. (2000). Multiple domains of occludin are involved in the regulation of paracellular permeability. J. Cell Biochem. 78:85–96.

    PubMed  CAS  Google Scholar 

  • Balda, M. S., Whitney, J. A., Flores, C., Gonzáles, S., Cereijido, M., and Matter, K. (1996). Functional dissociation of paracellular permeability and transepithelial resistance and disruption of the apical-basolateral intramembrane diffusion barrier by expression of a mutant tight junction membrane protein. J. Cell. Biol. 134:1031–1049.

    PubMed  CAS  Google Scholar 

  • Bauer, H. C., and Bauer, H. (2000). Neural induction of the blood–brain barrier: Still an enigma. Cell. Molec. Neurobiol. 20:13–28.

    PubMed  CAS  Google Scholar 

  • Bradbury, M. W. B. (1979). The Concept of a Blood–Brain Barrier, Wiley, Chichester, UK.

    Google Scholar 

  • Brightman, M. W. (1992) Ultrastructure of brain endothelium. In Bradbury, M. W. B. (ed.), Physiology and Pharmacology of the Blood–Brain Barrier, Springer-Verlag, Heidelberg, pp. 1–22.

    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.

    PubMed  CAS  Google Scholar 

  • Butt, A. M. (1995). Effect of inflammatory agents on electrical resistance across the blood–brain barrier in pial microvessels of anaesthetized rats. Brain Res. 696:145–50.

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Chen, K. C., and Nicholson, C. (2000). Spatial buffering of potassium ions in brain extracellular space. Biophys. J. 78:2776–2797.

    Article  PubMed  CAS  Google Scholar 

  • Conti, L., Cataudella, T., and Cattaneo, E. (2003). Neural stem cells: A pharmacological tool for brain diseases? Pharmacol. Res. 47:289–297.

    PubMed  CAS  Google Scholar 

  • Cserr, H. F., and Bundgaard, M. (1984). Blood–brain interface in vertebrates: A comparative approach. Am. J. Physiol. R246:277–288.

    Google Scholar 

  • Cserr, H. F., and Patlak, C. S. (1992) Secretion and bulk flow of interstitial fluid. In Bradbury, M. W. B. (ed.), Physiology and Pharmacology of the Blood–Brain Barrier, Springer Verlag, Berlin, pp. 245–261.

    Google Scholar 

  • Davson, H., and Segal, M. B. (1995). Physiology of the CSF and the Blood–Brain Barrier, CRC Press, New York.

    Google Scholar 

  • De Vries, H. E., Kuiper, J., de Boer, A. G., Van Berkel, T. J. C., and Breimer, D. D. (1997). The blood–brain barrier in neuroinflammatory diseases. Pharmacol. Rev. 49:143–155.

    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.

    PubMed  CAS  Google Scholar 

  • Deli, M. A., Ábrahám, C. S., Kataoka, Y., and Niwa, M. (2005). Permeability studies on in vitro BBB models: Physiology, pathology, pharmacology. Cell. Molec. Neurobiol. 25:59–127.

    PubMed  Google Scholar 

  • Demeule, M., Regina, A., Jodoin, J., Laplante, A., Dagenais, C., Berthelet, F., Moghrabi, A., and Beliveau, R. (2002). Drug transport to the brain: Key roles for the efflux pump P-glycoprotein in the blood–brain barrier. Vasc. Pharmacol. 38:339–348.

    CAS  Google Scholar 

  • Desai, S., Marroni, M., Cucullo, L., Bengez, L., Mayberg, M., Hosssain, M., Grant, G., and Janigro, D. (2002). Mechanisms of endothelial survival under shear stress. Endothelium 9:89–102.

    PubMed  CAS  Google Scholar 

  • Doolittle, N. D., Miner, M. E., Hall, W. A., Siegal, T., Jerome, E., Osztie, E., McAllister, L. D., Bubalo, J. S., Kraemer, D. F., Fortin, D., Nixon, R., Muldoon, L. L., and Neuwelt, E. A. (2000). Safety and efficacy of a multicenter study using intraarterial chemotherapy in conjunction with osmotic opening of the blood–brain barrier for the treatment of patients with malignant brain tumours. Cancer 88:637–647.

    PubMed  CAS  Google Scholar 

  • Duport, S., Robert, F., Muller, D., Grau, G., Parisi, L., and 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.

    PubMed  CAS  Google Scholar 

  • Easton, A. S., and Abbott, N. J. (2002). Bradykinin increases permeability by calcium and 5-lipoxygenase in the ECV304/C6 cell culture model of the blood–brain barrier. Brain Res. 953:157–169.

    PubMed  CAS  Google Scholar 

  • Easton, A. S., Sarker, M. H., and Fraser, P. A. (1997). Two components of blood–brain barrier disruption in the rat. J. Physiol. 503:613–623.

    PubMed  CAS  Google Scholar 

  • El Hafny, 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. 167:451–460.

    PubMed  CAS  Google Scholar 

  • El Hafny, B., Chappey, O., Piciotti, M., Debray, M., Boval, B., and Roux, F. (1997). Modulation of P-glycoprotein activity by glial factors and retinoic acid in an immortalized rat brain microvessel endothelial cell line. Neurosci. Lett. 236:107–111.

    PubMed  CAS  Google Scholar 

  • Engelhardt, B., and Risau, W. (1995). Development of the blood–brain barrier. In Greenwood, J., Begley, D. J., and Segal, M. B. (eds), New Concepts of the Blood–Brain Barrier, Plenum Press, New York and London, pp. 11–33.

    Google Scholar 

  • Fenstermacher, J., Nakata, H., Tajima, A., Yen, M.-H., Acuff, V., and Gruber, K. (1992). Structural, ultrastructural and functional correlations among local capillary systems within the brain. In: Segal, M. B. (ed.), Barriers and Fluids of the Eye and Brain, Macmillan Press, London, pp. 59–71.

    Google Scholar 

  • Gaillard, P. J., and de Boer, A. G. (2000). Relationship between permeability status of the blood–brain barrier and in vitro permeability coefficient of a drug. Eur. J. Pharm. Sci. 12:95–102.

    PubMed  CAS  Google Scholar 

  • Ghersi-Egea, J. F., Finnegan, W., Chen, J. L., and Fenstermacher, J. D. (1996). Rapid distribution of intraventricularly administered sucrose into cerebrospinal fluid cisterns via subarachnoid velae in rat. Neuroscience 75:1271–1288.

    PubMed  CAS  Google Scholar 

  • Haseloff, R. F., Blasig I. E., Bauer, H.-C., and Bauer, H. (2005). In search of the astrocytic factor(s) modulating blood–brain barrier functions in brain capillary endothelial cells in vitro. Cell. Molec. Neurobiol. 25:25–39.

    PubMed  CAS  Google Scholar 

  • Hickey, W. F. (2001). Basic principles of immunological surveillance of the normal central nervous system. Glia 36:118–124.

    PubMed  CAS  Google Scholar 

  • Hoheisel, D., Nitz, T., Franke, H., Wagner, J., Hakvoort, A., Tilling, T., and Galla, H. J. (1998). Hydrocortisone reinforces the blood–brain barrier properties in a serum free cell culture system. Biochem. Biophys. Res. Comm. 247:312–315.

    PubMed  CAS  Google Scholar 

  • Hosoya, K., Ohtsuki, S., and Terasaki, T. (2002). Recent advances in the brain-to-blood efflux transport across the blood–brain barrier. Int. J. Pharm. 248:15–29.

    PubMed  CAS  Google Scholar 

  • Huber, J. D., Egleton, R. D., and Davis, T. P. (2001). Molecular physiology and pathophysiology of tight junctions in the blood–brain barrier. Trends Neurosci. 24:719–725.

    PubMed  CAS  Google Scholar 

  • Hurst, R. D., and Fritz, I. B. (1996a). Properties of an immortalised vascular endothelial/glioma cell co-culture model of the blood–brain barrier. J. Cell. Physiol. 167:81–88.

    CAS  Google Scholar 

  • Hurst, R. D., and Fritz, I. B. (1996b) Nitric oxide-induced perturbations in a cell culture model of the blood–brain barrier. J. Cell. Physiol. 167:89–94.

    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. Commun. 261:108–112.

    PubMed  CAS  Google Scholar 

  • Joó, F., and Karnushina, I. (1973). A procedure for the isolation of capillaries from rat brain. Cytobios 8:41–48.

    PubMed  Google Scholar 

  • Kacem, K., Lacombe, P., Seylaz, J., and Bonvento, G. (1998). Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: A confocal microscopy study. Glia 23:1–10.

    PubMed  CAS  Google Scholar 

  • Konsman, J. P., Tridon, V., and Dantzer, R. (2000). Diffusion and action of intracerebroventricularly injected interleukin-1 in the CNS. Neuroscience 101:957–967.

    PubMed  CAS  Google Scholar 

  • Kraemer, D. F., Fortin, D., and Neuwelt, E. A. (2002). Chemotherapeutic dose intensification for treatment of malignant brain tumors: Recent developments and future directions. Curr. Neurol. Neurosci. Rep. 2:216–224.

    PubMed  Google Scholar 

  • Krämer, S. D., Abbott, N. J., and Begley, D. J. (2001). Biological models to study blood–brain barrier permeation. In Testa, B., van de Waterbeemd, H., Folkers, G., and Guy, R. (eds.), Pharmacokinetic Optimization in Drug Research: Biological, Physicochemical and Computational Strategies, Weinheim, Wiley-VCH, pp. 127–153.

    Google Scholar 

  • Krum, J. M., Kenyon, K. L., and Rosenstein, J. M. (1997). Expression of blood–brain barrier characteristics following neuronal loss and astroglial damage after administration of anti-Thy-1 immunotoxin. Exp. Neurol. 146:33–45.

    PubMed  CAS  Google Scholar 

  • Li, J. Y., Boado, R. J., and Pardridge, W. M. (2001). Blood–brain barrier genomics. J. Cereb. Blood Flow Metab. 21:61–68.

    PubMed  CAS  Google Scholar 

  • Mandel, L. J., Bacallao, R., and Zampighi, G. (1993). Uncoupling of the molecular “fence” and paracellular “gate” functions of epithelial tight junctions. Nature 361:552–555.

    PubMed  CAS  Google Scholar 

  • Male, D. K. (1992). Immunology of brain endothelium and the blood–brain barrier. In Bradbury, M. W. B. (ed.), Physiology and Pharmacology of the Blood–Brain Barrier, Springer Verlag, Berlin, pp. 397–415.

    Google Scholar 

  • Marroni, M., Marchi N., Cucullo, L., Abbott, N. J., Signorelli, K., and Janigro, D. (2003). Vascular and parenchymal mechanisms in multiple drug resistance: A lesson from human epilepsy. Curr. Drug Targets 4:279–304.

    Google Scholar 

  • Mayhan, W. G. (2001). Regulation of blood–brain barrier permeability. Microcirculation 8:89–104.

    PubMed  CAS  Google Scholar 

  • Mizuguchi, H., Utoguchi, N., and Mayumi, T. (1997). Preparation of glial extracellular matrix: A novel method to analyze glial–endothelial interaction. Brain Res. Protoc. 1:339–343.

    CAS  Google Scholar 

  • Moos, T. (2002). Brain iron homeostasis. Danish Med. Bull. 49:279–301.

    PubMed  CAS  Google Scholar 

  • Nagy, Z., Peters, H., and Hüttner, I. (1984). Fracture faces of cell junctions in cerebral endothelium during normal and hyperosmotic conditions. Lab. Invest. 50:313–322.

    PubMed  CAS  Google Scholar 

  • Nobles, M., Revest, P. A., Couraud, P.-O., and Abbott, N. J. (1995). Characteristics of nucleotide receptors that cause elevation of cytoplasmic calcium in immortalized rat brain endothelial cells (RBE4) and in primary cultures. Br. J. Pharmacol. 115:1245–1252.

    PubMed  CAS  Google Scholar 

  • Nobles, M., and Abbott, N. J. (1996). Adhesion and growth of brain microvascular endothelial cells on treated glass. Endothelium 4:297–307.

    CAS  Google Scholar 

  • Nobles, M., and Abbott, N. J. (1998). Modulation of the effects of extracellular ATP on [Ca2+]i in rat brain microvascular endothelial cells. Eur. J. Pharmacol. 361:19–127.

    Google Scholar 

  • Olesen, S.-P. (1989). An electrophysiological study of microvascular permeability and its modulation by chemical mediators. Acta Physiol. Scand. 136(Suppl. 579):1–28.

    Google Scholar 

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

    CAS  Google Scholar 

  • Pasqualini, R., Arap, W., and McDonald, D. M. (2002). Probing the structural and molecular diversity of tumor vasculature. Trends Molec. Med. 8:563–571.

    CAS  Google Scholar 

  • Perry, V. H., Anthony, D. C., Bolton, S. J., and Brown H. C. (1997). The blood–brain barrier and the inflammatory response. Mol. Med. Today 3:225–341.

    Google Scholar 

  • Plumb, J., McQuaid. S., Mirakur, M., and Kirk, J. (2002). Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis. Brain Path. 12:154–169.

    Article  Google Scholar 

  • Proescholdt, M. G., Hutto, B., Brady, L. S., and Herkenham, M. (2000). Studies of cerebrospinal fluid flow and penetration into brain following lateral ventricle and cisterna magna injections of the tracer [14C]inulin in rat. Neuroscience 2:577–592.

    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 

  • Rapoport, S. I. (2001). Advances in osmotic opening of the blood–brain barrier to enhance CNS chemotherapy. Expert Opin. Investig. Drugs 10:1809–1818.

    PubMed  CAS  Google Scholar 

  • Regina, A., Koman, A., Piciotti, M., El Hafny, B., Center, M. S., Bergmann, R., Couraud, P. O., and Roux, F. (1998). Mrp1 multidrug resistance-associated protein and P-glycoprotein expression in rat brain microvessel endothelial cells. J. Neurochem. 71:705–715.

    Article  PubMed  CAS  Google Scholar 

  • Reichel, A., Begley, D. J., and Abbott, N. J. (2003). An overview of in vitro techniques for blood–brain barrier studies. In Nag, S. (ed.), The Blood–Brain Barrier, Biology and Research Protocols, Humana Press, Totowa, New Jersey, pp. 307–324.

    Google Scholar 

  • Reinhart, C. A., and Gloor, S. M. (1997). Co-culture blood–brain barrier models and their use for pharmatoxicological screening. Toxicol. in Vitro 11:513–518.

    Google Scholar 

  • Rennels, M. L., Gregory, T. F., Blaumanis, O. R., Fujimoto, K., and Grady, P. A. (1985). Evidence for a ‘paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space. Brain Res. 326:47–63.

    PubMed  CAS  Google Scholar 

  • Revest, P. A., Abbott, N. J., and Gillespie, J. I. (1991). Receptor-mediated changes in intracellular [Ca2+] in cultured rat brain capillary endothelial cells. Brain Res. 549:159–161.

    PubMed  CAS  Google Scholar 

  • Risau, W., and Wolburg, H. (1990). Development of the blood–brain barrier. Trends. Neurosci. 13:174–178.

    PubMed  CAS  Google Scholar 

  • Rubin, L. L., Hall, D. 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.

    PubMed  CAS  Google Scholar 

  • Saunders, N. R. (1992). Ontogenetic development of brain barrier mechanisms. In Bradbury, M. W. B. (ed.), Physiology and Pharmacology of the Blood–Brain Barrier, Springer Verlag, Berlin, pp. 327–369.

    Google Scholar 

  • Schroeter, M. L., Mertsch, K., Giese, H., Muller, 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.

    PubMed  CAS  Google Scholar 

  • Schulze, C., and Firth, J. A. (1993). Immunohistochemical localization of adherens junction components in blood–brain barrier microvessels of the rat. J. Cell Sci. 104:773–782.

    PubMed  Google Scholar 

  • Segal, M. B., and Zlokovic, B. V. (1990). The Blood–Brain Barrier, Amino Acids and Peptides, Kluwer, Dordrecht, Boston, London.

    Google Scholar 

  • Sipos, I., Dömötör, E., Abbott, N. J., and Adam-Vizi, V. (2000). The pharmacology of nucleotide receptors on primary rat brain endothelial cells grown on a biological extracellular matrix: Effects on intracellular calcium concentration. Br. J. Pharmacol. 131:1195–1203.

    PubMed  CAS  Google Scholar 

  • Stanness, K. A., Westrum, L. E., Mascagni, P., Fornaciari, E., Nelson, J. A., Stenglein, S. G., and Janigro, D. (1997). Morphological and functional characterization of an in vitro blood–brain barrier model. Brain Res. 771:329–342.

    PubMed  CAS  Google Scholar 

  • Syková, E., Hansson, E., Rönnbäck, L., and Nicholson, C. (1998). Glial regulation of the neuronal microenvironment. In Laming, P. R., Syková, E., Reichenbach, A., Hatton, G. I., and Bauer, H. (eds.), Glial Cells: Their Role in Behaviour, Cambridge University Press, Cambridge, pp. 130–163.

    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.

    PubMed  CAS  Google Scholar 

  • Trepel, M., Arap, W., and Pasqualini, R. (2002). In vivo phage display and vascular heterogeneity: Implications for targeted medicine. Curr. Opin. Chem. Biol. 6:399–404.

    PubMed  CAS  Google Scholar 

  • Utsumi, H., Chiba, H., Kamimura, Y., Osanai, M., Igarashi, Y., Tobioka, H., Mori, M., and Sawada, N. (2000). Expression of GFRa-1, receptor for GDNF, in rat brain capillary during postnatal development of the BBB. Am. J. Physiol., Cell Physiol. 279:C361–C368.

    PubMed  CAS  Google Scholar 

  • Weller, R. O., Kida, S., and Zhang, E.-T. (1992). Pathways of fluid drainage form the brain—morphological aspects and immunological significance in rat and man. Brain Path. 2:277–284.

    CAS  Google Scholar 

  • Westergaard, E., and Brightman, M. W. (1973). Transport of proteins across segments of cerebral arterioles under normal conditions. J. Comp. Neurol. 152:17–44.

    PubMed  CAS  Google Scholar 

  • Wolburg, H., and Lippoldt, A. (2002). Tight junctions of the blood–brain barrier: Development, composition and regulation. Vasc. Pharmacol. 38:332–337.

    Google Scholar 

  • Yamagata, K., Tagami, M., Takenaga, F., Yamori, Y., Nara, Y., and Itoh, S. (2003). Polyunsaturated fatty acids induce tight junctions to form in brain capillary endothelial cells. Neuroscience 116:649–656.

    PubMed  CAS  Google Scholar 

  • Xaio, H., Banks, W. A., Niehoff, M. L., and Morley, J. E. (2001). Effect of LPS on the permeability of the blood–brain barrier to insulin. Brain Res. 896:36–42.

    PubMed  CAS  Google Scholar 

  • Zenker, D., Begley, D., Rübsamen-Waigmann, H., and von Briesen, H. (2001). Effects of macrophages on the blood–brain barrier properties of cultured brain capillary endothelial cells. J. Physiol. 531P:209P.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Blood-Brain Barrier Group, Wolfson Centre for Age Related Diseases, King’s College University of London, London, UK

    N Joan Abbott

  2. Blood–Brain Barrier Group, Wolfson Centre for Age Related Diseases, Hodgkin Building, King’s College, Guy’s Campus, London, SE1 1UL

    N Joan Abbott

Authors
  1. N Joan Abbott
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N Joan Abbott.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abbott, N.J. Dynamics of CNS Barriers: Evolution, Differentiation, and Modulation. Cell Mol Neurobiol 25, 5–23 (2005). https://doi.org/10.1007/s10571-004-1374-y

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-004-1374-y

Key words

Search

Navigation