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Measurement and Prediction of Blood-Brain Barrier Permeability

In vivo, in silico and in vitro approaches

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Blood—Brain Barrier

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Abstract

In the context of drug delivery, the brain is an unusual organ, since its capillary endothelium forms a barrier between the blood and the tissue, the blood-brain barrier (BBB) (Abbott and Romero, 1996). There are many reasons why the brain requires such a barrier while most other tissues do not, with the need for precise control of the brain microenvironment for reliable neural signalling being a major factor. The brain endothelial barrier has many features in common with epithelial barriers such as the intestinal epithelium. As with epithelial barriers, in vivo, in vitro and theoretical approaches can be used to study and predict the penetration of drugs across the BBB (Habgood et al. 2000, Krämer et al. 2000).

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References

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

    Google Scholar 

  • Abbott, N.J., Roux, F., Couraud, P.-O., and Begley, DJ., 1995, Studies on an immortalized brain endothelial cell line: differentiation, permeability and transport. In New Concepts of a Blood-Brain Barrier (J. Greenwood, D.J. Begley, and M.B. Segal, eds.), Plenum Press, New York, pp.239–249.

    Google Scholar 

  • Abbott, N.J., Chugani, D.C., Zaharachuk, G., Rosen, B.R., and Lo, E.H., 1998, Delivery of diagnostic agents into brain, and imaging CNS function. Adv. Drug Delivery Rev. 37: 253–277.

    Article  Google Scholar 

  • Abraham, M.H., and Chadha, H.S., 1996, Applications of a solvation equation to drug transport properties. In Lipophilicity in Drug Action and Toxicity (V. Pliska, B. Testa, and H.van de Waterbeemd, eds.), VCH, Weinheim, pp.311–337.

    Chapter  Google Scholar 

  • Abraham, M.H., Chadha, H.S., and Mitchell, R.C., 1994, Hydrogen bonding. 33. Factors that influence the distribution of solutes between blood and brain. J. Pharm. Sci. 83: 1257–1268.

    Article  PubMed  CAS  Google Scholar 

  • Abbruscato, T.J. and Davis, T.P., 1999, Combination of hypoxia/aglycemia compromises in vitro blood-brain barrier integrity. J. Pharmacol. Exp. Ther. 289: 668–675.

    PubMed  CAS  Google Scholar 

  • Anderson, P., Dolman, D.E.M., Nicol, A., and Abbott, N.J., 1999, Solute permeability, transendothelial electrical resistance and pore size of the paracellular pathway in a novel blood-brain barrier model, ECV304/C6. J. Physiol. 515P: 8P.

    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.

    Article  CAS  Google Scholar 

  • Begley, D.J., 1996, The blood-brain barrier: principles for targeting peptides and drugs to the central nervous system. J. Pharm. Pharmacol. 48: 136–146.

    Article  PubMed  CAS  Google Scholar 

  • Begley, D.J., 1999, Methods for determining drug transport in animals. In Brain Barrier Systems (O. Paulson, G. Moos Knudsen, T. Moos and A. Svejgaard, eds.), Alfred Benzon Symposium No 45, Munksgaard, Copenhagen, pp. 91–109.

    Google Scholar 

  • Begley, D.J., Khan, E.U., Rollinson, C, Abbott, N.J., Regina, A., and Roux, F., 2000, The role of brain extracellular fluid production and efflux mechanisms in drug transport to the brain. In The Blood-Brain Barrier and Drug Delivery to the CNS (D.J. Begley, M.W. Bradbury, and J. Kreuter (eds.), Marcel Dekker, New York, pp.93–108.

    Google Scholar 

  • Begley, D.J., Lechardeur, D., Chen, Z.-D., Rollinson, C, Bardoul, M., Roux, F., Sherman, D., and Abbott, N.J., 1996, Functional expression of P-glycoprotein in an immortalized cell line of rat brain endothelial cells, RBE4. J. Neurochem. 67: 988–995.

    Article  PubMed  CAS  Google Scholar 

  • Braun, A., Hämmerle, S., Suda, K., Rothen-Rutishauser, B., Günthert, M., Krämer, S.D., and Wundedrli-Allenspach, H., 2000, Cell cultures as tools in biopharmacy, Eur. J. Pharmaceut. Sci. 11Suppl. 2: S51–60.

    Article  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 

  • Cecchelli, R., Fenart, L., Buée-Scherrer, V., Dehouck, B., Descamps, L., Duhem, C., Torpier, G., and Dehouck, M.P., 2000, In vitro models of the blood-brain barrier and their use in drug development. In The Blood-Brain Barrier and Drug Delivery to the CNS (D.J. Begley, M.W. Bradbury, and J. Kreuter, eds.), Marcel Dekker, New York, pp. 65–75.

    Google Scholar 

  • Chishty, M., Reichel, A., Begley, D.J., and Abbott, N.J., 1997, Characterization of nucleoside transporters in RBE4, an immortalized rat brain endothelial cell line. J. Physiol. 501P: 31P.

    Google Scholar 

  • Chishty, M., Reichel, A., Begley, D.J., and Abbott, N.J., 1998, Glial factors induce bloodbrain barrier-like L-leucine transport in the non-brain endothelial cell line ECV304. J. Physiol. 505P: 55–56P.

    Google Scholar 

  • Chishty, M., Reichel, A., Abbott, N.J. and Begley, DJ., 2001, Stimulation of P-glycoproteinmediated efflux by H1 and adenosine receptor ligands in RBE4 cells, as in vitro model of the blood-brain barrier. J. Physiol. P (in press).

    Google Scholar 

  • Cordon-Cardo, C., O’Brien, J.P., Casala, D., Rittman-Grauer, L., Biedler, J.L., Melamed, M.R., and Bertino, J.R., 1989, Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc. Natl. Acad. Sci. USA 86: 695–698.

    Article  PubMed  CAS  Google Scholar 

  • Cserr, H.F., Cooper, D.N., Suri, P.K., and Patlak, C.S., 1981, Efflux of radiolabelled polyethylene glycols and albumin from rat brain. Am. J. Physiol. 240: F319–328.

    PubMed  CAS  Google Scholar 

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

    Google Scholar 

  • Dehouck, B., Fenart, L., Dehouck, M.P., Pierce, A., Torpier, G., and Ceccheli, R., 1997, A new function for the LDL receptor: transcytosis of LDL across the blood-brain barrier. J. Cell Biol. 138: 877–889.

    Article  PubMed  CAS  Google Scholar 

  • Dehouck, M.-P., Dehouck, B., Schluep, C., Lemaire, M., and Cecchelli, R., 1995, Drug transport to the brain: comparison between in vitro and in vivo models of the blood-brain barrier. Eur. J. Pharmaceut. Sci. 3: 357–365.

    Article  CAS  Google Scholar 

  • Dehouck, M.P., Jolliet-Riant, P., Bree, F., Fruchart, J.-C., Cecchelli, R., and Tillement, J.-P., 1992, Drug transfer across the blood-brain barrier: correlation between in vitro and in vivo models. J. Neurochem. 58: 1790–1797.

    Article  PubMed  CAS  Google Scholar 

  • Descamps, L., Dehouck, M.P., Torpier, G., and Ceccheli, R., 1996, Receptor-mediated transcytosis of transferrin through blood-brain barrier endothelial cells. Am. J. Physiol. 270: H1149–1158.

    PubMed  CAS  Google Scholar 

  • Dolman, D.E.M., Anderson, T., Rollinson, C, and Abbott, N.J., 1997, Characterisation of a new in vitro model of the blood-brain barrier (BBB). J. Physiol. 505P: 56–57P.

    Google Scholar 

  • Easton, A.S., and Abbott, N.J., 1998, The effects of bradykinin on a cell culture model of the blood-brain barrier (BBB). J. Physiol. 505P, 49–50P.

    Google Scholar 

  • El Hafhy, 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.

    Article  Google Scholar 

  • Franke, H., Galla, H.-J., and Beuckmann, C.T., 1999, An improved low permeability in-vitro model of the blood-brain barrier: transport studies on retinoids, sucrose, halperidol, caffeine and mannitol. Brain Res. 818: 65–71.

    Article  PubMed  CAS  Google Scholar 

  • Geer, C.P., and Grossman, S.A., 1997, Interstitial fluid flow along white.matter tracts: a potentially important mechanism for the dissemination of primary brain tumours. J. Neuro-oncology 32: 193–201.

    Article  CAS  Google Scholar 

  • Grant, G.A., Abbott, N.J., and Janigro, D., 1998, Understanding the physiology of the blood-brain barrier: in vitro models. News in Physiol. Sci. 13: 287–293.

    CAS  Google Scholar 

  • Gratton, J.A., Abraham, M.H., Bradbury, M.W., and Chadha, H.S., 1997, Molecular factors influencing drug transfer across the blood-brain barrier. J. Pharm.Pharmacol. 49: 1211–1216.

    Article  PubMed  CAS  Google Scholar 

  • Greenwood J, Pryce G, Devine L, Male DK, dos Santos WLC, Calder VL, Adamson P (1996) SV40 large T immortalized cell lines of the rat blood-brain and blood-retinal barriers retain their phenotypic and immunological characteristics. J. Neuroimmunol. 71, 51–63.

    Article  PubMed  CAS  Google Scholar 

  • Habgood, M.D., Begley, D.J., and Abbott, N.J., 2000, Determinants of passive drug entry into the central nervous system. Cell. & Molecular Neurobiology 20: 231–253.

    Article  CAS  Google Scholar 

  • Hidalgo, I.J., and Li, J., 1996, Carrier-medited transport and efflux mechanisms in Caco-2 cells. Adv. Drug Deliv. Rev. 22: 53–66.

    Article  CAS  Google Scholar 

  • Homma, M., Suzuki, H., Kusuhara, H., Naito, M., Tsuro, T., and Sugiyama, Y., 1999, High affinity efflux transport system for glutathione conjugates on the luminal membrane of a mouse brain capillary endothelial cell line (MBEC4). J. Pharmacol. Exp. Ther. 288: 198–203.

    PubMed  CAS  Google Scholar 

  • Horio, M., Chin, K.V., Currier, S.J., Goldenberg, S., Williams, C., Pastan, I., Gottesmann, M.M., Handlers, J., 1989, Transepithelial transport of drugs by the multidrug transporter in cultured Madin-Darby Canine Kidney epithelia. J. Biol. Chem. 264: 14880–14884.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Huwyler, J., Froidevaux, S., Roux, F., Eberle, A.N., 1999, Characterizastion of transferrinreceptor in an immortalized cell line of rat brain endothelial cells, RBE4. J. Recept. Signal. Transduct. Res. 19: 729–739.

    Article  PubMed  CAS  Google Scholar 

  • Khan, E.U., Begley, D.J., and Abbott, N.J., 1999, RBE4, a model system for assessing drug interactions with P-glycoprotein at the blood-brain barrier. J. Physiol. 520P: 86P.

    Google Scholar 

  • Khan, E.U., Reichel, A., Begley, D.J., Roffey, S.J., Jezequel, S.G., and Abbott, N.J., 1997, The effect of drug lipophilicity on P-glycoprotein-mediated colchicine efflux at the blood-brain barrier. Int. J. Clin. Pharm. & Therap. 36: 84–86.

    Google Scholar 

  • Kiessling, F., Kartenbeck, J., and Haller, C, 1999, Cell-cell contacts in the human cell line ECV304 exhibit both endothelial and epithelial characteristics. Cell & Tissue Res. 297: 131–140.

    Article  CAS  Google Scholar 

  • Krämer, S.D., Abbott, N.J., and Begley, D.J., 2000, Biological models to study blood-brain barrier permeation. In Pharmacokinetic Optimization in Drug Research: Biological, Physiochemical and Computational Strategies (B. Testa, H.van de Waterbeemd, G. Folkers, and R. Guy, eds.), Wiley-VHCA, Zurich (in press).

    Google Scholar 

  • Levin, V.A., 1980, Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J. Med. Chem. 23: 682–684.

    Article  PubMed  CAS  Google Scholar 

  • Mendonca, L.L.F., Smith, R., Hughes, G.R.V., Dolman, D.E.M., Dobbie, M., Hurst, R.D. and Abbott, N.J. (2000), Serum antibodies from patients with neuropsychiatric lupus erythematosus cause activation and damage to an in vitro blood-brain barrier model. J. Physiol. 525P, 38P.

    Google Scholar 

  • Mertsch, K., Haseloff, R.F., and Blasig, I.E., 1997, Investigation of radical scavengers by using an in vitro model of blood-brain barrier. Devel. Animal Vet. Sci. 27: 881–886.

    Google Scholar 

  • Minn, A., El-Bachá, R.D.S., Bayol-Denizot, C., Lagrange, P., Suleman, F.G., Gradinaru, D., 2000, Drug metabolism in brain: benefits and risks. In The Blood-Brain Barrier and Drug Delivery to the CNS (D.J. Begley, M.W. Bradbury, and J. Kreuter (eds.), Marcel Dekker, New York, pp.145–170.

    Google Scholar 

  • Muruganandam, A., Herx, L.M., Monette, R., Durkin, J.P., and Stanimirovic, D.B., 1997, Development of immortalized cerebrovascular endothelial cell line as an in vitro model of the human blood-brain barrier. FASEB J. 11: 1187–1197.

    PubMed  CAS  Google Scholar 

  • Nicholson, C., and Syková, E., 1998, Extracellular space structure revealed by diffusion analysis. Trends Neurosci. 21: 207–215.

    Article  PubMed  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: 119–127.

    Article  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.

    Article  PubMed  CAS  Google Scholar 

  • Oldendorf, W.H., 1974, Lipid solubility and drug penetration of the blood-brain barrier. Proc. Soc. Exp. Biol. Med. 147: 813–816.

    PubMed  CAS  Google Scholar 

  • Pastan, I., Gottesman, M.M., Ueda, K., Lovelace, E., Rutherford, A.V., and Willingham, M.C., 1988, A retrovirus carrying MDR1 cDNA confers multidrug resistance and polarized expression of P-glycoprotein in MDCK cells. Proc. Natl. Acad. Sci. USA 85: 4486–4490.

    Article  PubMed  CAS  Google Scholar 

  • Pardridge, W.M., 1998, CNS drug design based on principles of blood brain barrier transport. J. Neurochem. 70: 1781–1792.

    Article  PubMed  CAS  Google Scholar 

  • Polli, J.W., Humphreys, J.E., Wring, S.A., Burnette, T.C., Read, K.D., Hersey, A., Butina, D., Bertolotti, L., Pugnaghi, F., and Serabjit-Singh, C.S., 2000,. A comparison of MDCK and bovine brain endothelial cells (BBECs) as a blood-brain barrier screen in early drug discovery. In Progress in Reduction, Refinement and Replacement of Animal Experimentation (M. Balls, A.-M.van Zeller, and M. Haider, eds.), Elsevier, New York, pp.271–289.

    Google Scholar 

  • Quinonéro, J., Tchélingérian, J.-L., Vignais, L., Foignant-Chaverot, N., Colin, C, Horellou, P., Liblau, R., Barbin, G., Strosberg, A.D., Jacque, C., and Couraud P-O., 1997, Gene transfer to the central nervous system by transplantation of cerebral endothelial cells. Gene Therapy 4: 111–119.

    Article  PubMed  Google Scholar 

  • Reeve-Chen, Z.-D., and Abbott, N.J., 1998, Glial factors increase the functional activity of P-glycoprotein in immortalised rat brain endothelial cells (RBE4). J. Physiol. 505P: 55P.

    Google Scholar 

  • Regina, A., Roux, F., Revest, P.A., 1997, Glucose transport in immortalized rat brain capillary endothelial cells in vitro; transport activity and GLUT-1 expression. Biochim. Biophys. Acta 1335: 135–143.

    Article  PubMed  CAS  Google Scholar 

  • Regina, A., Romero, I.A., Greenwood, J., Adamson, P., Bourre, J.-M., Couraud, P.-O., and Roux, F., 1999, Dexamethasone regulation of P-glycoprotein activity in an immortalized rat brain endothelial cell line, GPNT. J. Neurochem. 73: 1954–1963.

    PubMed  CAS  Google Scholar 

  • Reichel, A., Begley, D.J., and Abbott, N.J., 2000, Carrier-mediated delivery of metabotropic glutamate receptor ligands to the CNS: Structural tolerance and potential of the L-system amino acid transporter at the blood-brain barrier. J. Cerebral Blood Flow & Metab. 20: 168–174.

    Article  CAS  Google Scholar 

  • Reichel, A., Aleshaiker, A., Begley, DJ., and Abbott, N.J., 1996, In vitro screening for drugs interacting with P-glycoprotein drug efflux using immortalised rat brain endothelial cells (RBE4). J. Physiol. 491P: 36P.

    Google Scholar 

  • Reichel, A., Begley, D.J., Abbott, N.J. and Chichty, M., 2001, Relationship between affinity for nucleoside transporters at the blood-brain barrier and physicochemical properties of adenosine analogues. J. Physiol. (Proc) in press..

    Google Scholar 

  • Reichel, A., Chishty, M., Begley, DJ., and Abbott, N.J., 1998, Carrier-mediated transport of S-adenosylmethionine across the blood-brain barrier in vitro. J. Physiol. 505P: 48P.

    Google Scholar 

  • Reichel, A., Reeve-Chen, Z.-D., Begley, DJ., and Abbott, N.J., 1996, A method to assess functional activity of P-glycoprotein in vitro based on the energy requirements of the transporter. Adv. Exp. Med. Biol. 183–187.

    Google Scholar 

  • Reichel, A., Siva, J., Abbott, N.J., and Begley, D.J., 1999, Affinity for the P-glycoprotein efflux pump at the blood-brain barrier may explain the absence of central side effects of some modern antihistamines. J. Physiol 515P: 4–5P.

    Google Scholar 

  • Rist, R.J., Romero, I.A., Chan, M.W.K., Couraud, P.-O., Roux, F., and Abbott, N.J., 1997, F-actin cytoskeleton and sucrose permeability of immortalised brain microvascular endothelial cell monolayers: effects of cAMP and astrocytic factors. Brain Res. 768: 10–18.

    Article  PubMed  CAS  Google Scholar 

  • Rollinson, C., and Abbott, N.J., 1998, Comparison of the phenotype of immortalized brain endothelial cells (RBE4) with in situ brain endothelium: a lectin and antibody study. J. Physiol. 505: 54–55P.

    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 

  • Saheki, A., Terasaki, T., Tamai, I., and Tsuji, A., 1994, In vivo and in vitro blood-brain barrier transport of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors. Pharmaceut. Res. 11: 305–311.

    Article  CAS  Google Scholar 

  • Sisodiya, S.M., Lin, W.-R., Squier, M.V. and Thorn, M., 2001, Multidrug resistance protein 1 in focal cortical dysplasia. Lancet 357: 42–43.

    Article  PubMed  CAS  Google Scholar 

  • Smith, Q.R., and Stoll, J., 1999, Molecular characterization of amino acid transporters at the blood-brain barrier. In Brain Barrier Systems (O. Paulson, G. Moos Knudsen, T. Moos and A. Svejgaard, eds.), Alfred Benzon Symposium No 45, Munksgaard, Copenhagen, pp.303–317.

    Google Scholar 

  • Suda, K., Rothen-Rutishauser, B.M., Günthert, M., and Wunderli-Allenspach, H., 1999, Confocal laser scanning microscopy as a potent tool for the characterisation of blood-brain barrier cell culture models. J. Physiol. 520P, 85P.

    Google Scholar 

  • Sugiyama Y., Kusuhara, H., Suzuki, H., 1999, Kinetic and biochemical analysis of carriermediated efflux of drugs through the blood-brain and blood-cerebrospinal fluid barriers: importance in the drug delivery to the brain. J. Controlled Release 62: 179–186.

    Article  CAS  Google Scholar 

  • Suzuki, H., Terasaki, T., and Sugiyama, Y. (1997) Role of efflux transport across the blood-brain barrier and blood-cerebrospinal fluid barrier on the disposition of xenobiotics in the central nervous system. Adv. Drug Delivery Rev. 25: 257–285.

    Article  CAS  Google Scholar 

  • Tsuji, A., 2000, Specific mechanisms for transporting drugs into the brain. In The Blood-Brain Barrier and Drug Delivery to the CNS (DJ. Begley, M.W. Bradbury, and J. Kreuter, eds.), Marcel Dekker, New York, pp.121-144.

    Google Scholar 

  • Tatsuta, T., Naito, M., Oh-hara, T., Sugawara, I., Tsuruo, T., 1992, Functional involvement of P-glycoprotein in blood-brain barrier. J. Biol. Chem. 28: 20383–20391.

    Google Scholar 

  • Van Asperen, J., Mayer, U., Van Tellingen, O., and Beijnen, J.H., 1997, The functional role of P-glycoprotein in the blood-brain barrier. J. Pharm. Sci. 86: 881–884.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Blood-Brain Barrier Group, Centre for Neuroscience Research, King’s College London, London, SEI 1UK, UK

    N. Joan Abbott, Mansoor Chishty, Janet A. Taylor & David J. Begley

  2. Bioanalysis and Drug Metablolism, GlaxoSmithKline, Ware, Herts, SG12 0DP, UK

    Kevin D. Read

  3. Schering AG, Research Pharmacokinetics, Muellerstrasse 178, D-13342, Berlin, Germany

    Andreas Reichel

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  1. N. Joan Abbott
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  2. Andreas Reichel
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  3. Mansoor Chishty
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  1. Israel Institute for Biological Research, Ness-Ziona, Israel

    David Kobiler , Shlomo Lustig  & Shlomo Shapira ,  & 

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Abbott, N.J., Reichel, A., Chishty, M., Read, K.D., Taylor, J.A., Begley, D.J. (2001). Measurement and Prediction of Blood-Brain Barrier Permeability. In: Kobiler, D., Lustig, S., Shapira, S. (eds) Blood—Brain Barrier. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0579-2_4

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