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The Blood-Brain Barrier

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Abstract

The concept of a blood-brain barrier (BBB) dates back to experiments performed by Paul Ehrlich. Using “intravital tracers” which change their color depending on their oxidative state, he intended to estimate the oxygen consumption of the bodily organs. An important prerequisite of this approach, however, would have been an equal distribution of these tracers at the beginning of the experiment, but this was not what he found: Hydrophilic dyes uniformly did not reach the parenchyma, which led his student, the Berlin physician Lewandowski to claim that the capillary wall provides a barrier for certain molecules in the brain, but it was not before the golden era of electron microscopy that Reese and Karnovsky detected what they called “morphological barriers” of the BBB. In this article, we provide an overview of what maintains barrier function for blood-molecules, clarify that a BBB for solutes is neither mechanistically equal to a barrier for immune cells nor in regard to the sites of entry (capillaries versus post-capillary venules), formulate areas of lack of knowledge and consequently, raise open questions to be addressed in the future.

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References

  • Abbott NJ, Rönnbäck L, Hansson E (2006) Astrocyte–endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 7:41–53

    Article  PubMed  CAS  Google Scholar 

  • Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ (2010) Structure and function of the blood-brain barrier. Neurobiol Dis 37:13–25

    Article  PubMed  CAS  Google Scholar 

  • Abbruscato TJ, Lopez SP, Mark KS, Hawkins BT, Davis TP (2002) Nicotine and cotinine modulate cerebral microvascular permeability and protein expression of ZO-1 through nicotinic acetylcholine receptors expressed on brain endothelial cells. J Pharm Sci 91:2525–2538

    Article  PubMed  CAS  Google Scholar 

  • Agrawal S, Anderson P, Durbeej M, van Rooijen N, Ivars F, Opdenakker G, Sorokin LM (2006) Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis. J Exp Med 203:1007–1019

    Article  PubMed  CAS  Google Scholar 

  • Alvarez JI, Dodelet-Devillers A, Kebir H, Ifergan I, Fabre PJ, Terouz S, Sabbagh M, Wosik K, Bourbonnière L, Bernard M, van Horssen J, de Vries HE, Charron F, Prat A (2011) The Hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence. Science 334:1727–1731

    Article  PubMed  CAS  Google Scholar 

  • Armulik A, Abramsson A, Betsholtz C (2005) Endothelial/pericyte interactions. Circ Res 97:512–523

    Article  PubMed  CAS  Google Scholar 

  • Armulik A, Genove G, Mäe M, Nisancioglu MH, Wallgard E, Niaudet C, He L, Norlin J, Lindblom P, Strittmatter K, Johansson BR, Betsholtz C (2010) Pericytes regulate the blood-brain barrier. Nature 468:557–561

    Article  PubMed  CAS  Google Scholar 

  • Arthur FE, Shivers RR, Bowman PD (1987) Astrocyte-mediated induction of tight junctions in brain capillary endothelium: an efficient in vitro model. Brain Res 433:155–159

    PubMed  CAS  Google Scholar 

  • Aurrand-Lions MA, Duncan L, Du Pasquier L, Imhof BA (2000) Cloning of JAM-2 and JAM-3: an emerging junctional adhesion molecular family? Curr Top Microbiol Immunol 251:91–98

    Article  PubMed  CAS  Google Scholar 

  • Bartholomäus I, Kawakami N, Odoardi F, Schläger C, Miljkovic D, Ellwart JW, Klinkert WE, Flügel-Koch C, Issekutz TB, Wekerle H, Flügel A (2009) Effector T cell interactions with meningeal vascular structures in nascent autoimmune CNS lesions. Nature 462:94–98

    Article  PubMed  Google Scholar 

  • Bechmann I, Mor G, Nilsen J, Eliza M, Nitsch R, Naftolin F (1999) FasL (CD95L, Apo1L) is expressed in the normal rat and human brain: evidence for the existence of an immunological brain barrier. Glia 27:62–74

    Article  PubMed  CAS  Google Scholar 

  • Bechmann I, Priller J, Kovac A, Böntert M, Wehner T, Klett FF, Bohsung J, Stuschke M, Dirnagl U, Nitsch R (2001) Immune surveillance of mouse brain perivascular spaces by blood-borne macrophages. Eur J Neurosci 14:1651–1658

    Article  PubMed  CAS  Google Scholar 

  • Bechmann I, Galea I, Perry VH (2007) What is the blood-brain barrier (not)? Trends Immunol 28(1):5–11

    Article  PubMed  CAS  Google Scholar 

  • Begley DJ (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 DJ (2004) ABC transporters and the blood–brain barrier. Curr Pharm Des 10:1295–1312

    Article  PubMed  CAS  Google Scholar 

  • Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R, Zlokovic BV (2010) Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron 68:409–427

    Article  PubMed  CAS  Google Scholar 

  • Bernacki J, Dobrowolska A, Nierwińska K, Małecki A (2008) Physiology and pharmacological role of the blood-brain barrier. Pharmacol Rep 60:600–622

    PubMed  CAS  Google Scholar 

  • Betz AL, Firth JA, Goldstein GW (1980) Polarity of the blood-brain barrier: distribution of enzymes between the luminal and antiluminal membranes of brain capillary endothelial cells. Brain Res 192:17–28

    Article  PubMed  CAS  Google Scholar 

  • Bodor N, Buchwald P (2002) Barriers to remember: brain-targeting chemical delivery systems and Alzheimer’s disease. Drug Discov Today 7:766–774

    Article  PubMed  CAS  Google Scholar 

  • Bouldin TW, Krigman MR (1975) Differential permeability of cerebral capillary and choroid plexus to lanthanum ion. Brain Res 99:444–448

    Article  PubMed  CAS  Google Scholar 

  • Bradbury MW, Stubbs J, Hughes IE, Parker P (1963) The distribution of potassium, sodium, chloride and urea between lumbar cerebrospinal fluid and serum in human subjects. Clin Sci 25:97–105

    PubMed  CAS  Google Scholar 

  • Cardoso FL, Brites D, Brito MA (2010) Looking at the blood-brain barrier: molecular anatomy and possible investigation approaches. Brain Res Rev 64:328–363

    Article  PubMed  CAS  Google Scholar 

  • Claudio L, Kress Y, Norton WT, Brosnan CF (1989) Increased vesicular transport and decreased mitochondrial content in blood–brain barrier endothelial cells during experimental autoimmune encephalomyelitis. Am J Pathol 135:1157–1168

    PubMed  CAS  Google Scholar 

  • Daneman R, Agalliu D, Zhou L, Kuhnert F, Kuo CJ, Barres BA (2009) Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis. Proc Natl Acad Sci U S A 106:641–646

    Article  PubMed  CAS  Google Scholar 

  • Daneman R, Zhou L, Kebede AA, Barres BA (2010) Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 468:562–566

    Article  PubMed  CAS  Google Scholar 

  • Dangerfield J, Larbi KY, Huang MT, Dewar A, Nourshargh S (2002) PECAM-1 (CD31) homophilic interaction up-regulates alpha6beta1 on transmigrated neutrophils in vivo and plays a functional role in the ability of alpha6 integrins to mediate leukocyte migration through the perivascular basement membrane. J Exp Med 196:1201–1211

    Article  PubMed  CAS  Google Scholar 

  • Dean M, Rzhetsky A, Allikmets R (2001) The human ATP-binding cassette (ABC) transporter superfamily. Genome Res 11:1156–1166

    Article  PubMed  CAS  Google Scholar 

  • Dente CJ, Steffes CP, Speyer C, Tyburski JG (2001) Pericytes augment the capillary barrier in in vitro cocultures. J Surg Res 97:85–91

    Article  PubMed  CAS  Google Scholar 

  • Dogrukol-Ak D, Kumar VB, Ryerse JS, Farr SA, Verma S, Nonaka N, Nakamachi T, Ohtaki H, Niehoff ML, Edwards JC, Shioda S, Morley JE, Banks WA (2009) Isolation of peptide transport system-6 from brain endothelial cells: therapeutic effects with antisense inhibition in Alzheimer and stroke models. J Cereb Blood Flow Metab 29:411–422

    Article  PubMed  CAS  Google Scholar 

  • Ebnet K, Suzuki A, Ohno S, Vestweber D (2004) Junctional adhesion molecules (JAMs): more molecules with dual functions? J Cell Sci 117:19–29

    Article  PubMed  CAS  Google Scholar 

  • Ehrlich P (1885) Das Sauerstoffbedürfnis des Organismus. In: Eine Farbenanalytische Studie, Hirschwald, Berlin

  • Erickson KK, Sundstrom JM, Antonetti DA (2007) Vascular permeability in ocular disease and the role of tight junctions. Angiogenesis 10:103–117

    Article  PubMed  Google Scholar 

  • Fanning AS, Jameson BJ, Jesaitis LA, Anderson JM (1998) The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem 273:29745–29753

    Article  PubMed  CAS  Google Scholar 

  • Feldman GJ, Mullin JM, Ryan MP (2005) Occludin: structure, function and regulation. Adv Drug Deliv Rev 57:883–917

    Article  PubMed  CAS  Google Scholar 

  • Felts PA, Smith KJ (1996) Blood-brain barrier permeability in astrocyte-free regions of the central nervous system remyelinated by Schwann cells. Neuroscience 75:643–655

    Article  PubMed  CAS  Google Scholar 

  • Fischer S, Wobben M, Marti HH, Renz D, Schaper W (2002) Hypoxia-induced hyperpermeability in brain microvessel endothelial cells involves VEGF-mediated changes in the expression of zonula occludens-1. Microvasc Res 63:70–80

    Article  PubMed  CAS  Google Scholar 

  • Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S (1993) Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 123:1777–1788

    Article  PubMed  CAS  Google Scholar 

  • Furuse M, Itoh M, Hirase T, Nagafuchi A, Yonemura S, Tsukita S (1994) Direct association of occludin with ZO-1 and its possible involvement in the localization of occludin at tight junctions. J Cell Biol 127:1617–1626

    Article  PubMed  CAS  Google Scholar 

  • Gingrich MB, Traynelis SF (2000) Serine proteases and brain damage—is there a link? Trends Neurosci 23:399–407

    Article  PubMed  CAS  Google Scholar 

  • Gumbiner B, Lowenkopf T, Apatira D (1991) Identification of a 160-kDa polypeptide that binds to the tight junction protein ZO-1. Proc Natl Acad Sci U S A 88:3460–3464

    Article  PubMed  CAS  Google Scholar 

  • Hansen AJ (1985) Effect of anoxia on ion distribution in the brain. Physiol Rev 65:101–148

    PubMed  CAS  Google Scholar 

  • Hawkins BT, Davis TP (2005) The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57:173–185

    Article  PubMed  CAS  Google Scholar 

  • Hirase T, Staddon JM, Saitou M, Ando-Akatsuka Y, Itoh M, Furuse M, Fujimoto K, Tsukita S, Rubin LL (1997) Occludin as a possible determinant of tight junction permeability in endothelial cells. J Cell Sci 110:1603–1613

    PubMed  CAS  Google Scholar 

  • Huber JD, Egleton RD, Davis TP (2001) Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier. Trends Neurosci 24:719–725

    Article  PubMed  CAS  Google Scholar 

  • Igarashi Y, Utsumi H, Chiba H, Yamada-Sasamori Y, Tobioka H, Kamimura Y, Furuuchi K, Kokai Y, Nakagawa T, Mori M, 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

    Article  PubMed  CAS  Google Scholar 

  • Inoko A, Itoh M, Tamura A, Matsuda M, Furuse M, Tsukita S (2003) Expression and distribution of ZO-3, a tight junction MAGUK protein, in mouse tissues. Genes Cells 8:837–845

    Article  PubMed  CAS  Google Scholar 

  • Itoh M, Nagafuchi A, Yonemura S, Kitani-Yasuda T, Tsukita S, Tsukita S (1993) The 220-kD protein colocalizing with cadherins in non-epithelial cells is identical to ZO-1, a tight junction-associated protein in epithelial cells: cDNA cloning and immunoelectron microscopy. J Cell Biol 121:491–502

    Article  PubMed  CAS  Google Scholar 

  • Jaeger CB, Blight AR (1997) Spinal cord compression injury in guinea pigs: structural changes of endothelium and its perivascular cell associations after blood-brain barrier breakdown and repair. Exp Neurol 144:381–399

    Article  PubMed  CAS  Google Scholar 

  • Janzer RC, Raff MC (1987) Astrocytes induce blood–brain barrier properties in endothelial cells. Nature 325:253–257

    Article  PubMed  CAS  Google Scholar 

  • Johnson-Léger C, Imhof BA (2003) Forging the endothelium during inflammation: pushing at a half-open door? Cell Tissue Res 314:93–105

    Article  PubMed  Google Scholar 

  • Kastin A, Pan W (2003) Peptide transport across the blood–brain barrier. Prog Drug Res 61:79–100

    PubMed  CAS  Google Scholar 

  • Kofuji P, Newman EA (2004) Potassium buffering in the central nervous system. Neuroscience 129:1045–1056

    Article  PubMed  CAS  Google Scholar 

  • Kubota K, Furuse M, Sasaki H, Sonoda N, Fujita K, Nagafuchi A, Tsukita S (1999) Ca(2+)-independent cell-adhesion activity of claudins, a family of integral membrane proteins localized at tight junctions. Curr Biol 9:1035–1038

    Article  PubMed  CAS  Google Scholar 

  • Lee SW, Kim WJ, Choi YK, Song HS, Son MJ, Gelman IH, Kim YJ, Kim KW (2003) SSeCKS regulates angiogenesis and tight junction formation in blood-brain barrier. Nat Med 9:900–906

    Article  PubMed  CAS  Google Scholar 

  • Lewandowski M (1900) Zur Lehre von der Cerebrospinalflüssigkeit. Z Klin Med 40:480–494

    Google Scholar 

  • Li F, Lan Y, Wang Y, Wang J, Yang G, Meng F, Han H, Meng A, Wang Y, Yang X (2011) Endothelial Smad4 maintains cerebrovascular integrity by activating N-cadherin through cooperation with Notch. Dev Cell 20:291–302

    Article  PubMed  CAS  Google Scholar 

  • Liebner S, Kniesel U, Kalbacher H, Wolburg H (2000) Correlation of tight junction morphology with the expression of tight junction proteins in blood-brain barrier endothelial cells. Eur J Cell Biol 79:707–717

    Article  PubMed  CAS  Google Scholar 

  • Liebner S, Corada M, Bangsow T, Babbage J, Taddei A, Czupalla CJ, Reis M, Felici A, Wolburg H, Fruttiger M, Taketo MM, von Melchner H, Plate KH, Gerhardt H, Dejana E (2008) Wnt/beta-catenin signaling controls development of the blood-brain barrier. J Cell Biol 183:409–417

    Article  PubMed  CAS  Google Scholar 

  • Liu X, Tu M, Kelly RS, Chen C, Smith BJ (2004) Development of a computational approach to predict blood-brain barrier permeability. Drug Metab Dispos 32:132–139

    Article  PubMed  CAS  Google Scholar 

  • Liu Y, Wada R, Yamashita T, Mi Y, Deng CX, Hobson JP, Rosenfeldt HM, Nava VE, Chae SS, Lee MJ, Liu CH, Hla T, Spiegel S, Proia RL (2008) Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J Clin Invest 106:951–961

    Article  Google Scholar 

  • Liu WY, Wang ZB, Zhang LC, Wei X, Li L (2012) Tight junction in blood-brain barrier: an overview of structure, regulation, and regulator substances. CNS Neurosci Ther 18:609–615

    Article  PubMed  CAS  Google Scholar 

  • Martìn-Padura I, Lostaglio S, Schneemann M, Williams L, Romano M, Fruscella P, Panzeri C, Stoppacciaro A, Ruco L, Villa A, Simmons D, Dejana E (1998) Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol 142:117–127

    Article  PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Muller WA (2003) Leukocyte-endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol 24:327–334

    PubMed  CAS  Google Scholar 

  • Murphy E, Sturm E (1923) Conditions determining the transplantability of tissues in the brain. J Exp Med 38:183–197

    Article  PubMed  CAS  Google Scholar 

  • Nadal A, Fuentes E, Pastor J, McNaughton PA (1995) Plasma albumin is a potent trigger of calcium signals and DNA synthesis in astrocytes. Proc Natl Acad Sci U S A 92:1426–1430

    Article  PubMed  CAS  Google Scholar 

  • Nag S, Begley DJ (2005) Blood–brain barrier, exchange of metabolites and gases. In: Kalimo H (ed) Pathology and genetics. Cerebrovascular diseases. ISN Neuropath. Press, Basel, pp 22–29

    Google Scholar 

  • Nitta T, Hata M, Gotoh S, Seo Y, Sasaki H, Hashimoto N, Furuse M, Tsukita S (2003) Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol 161:653–660

    Article  PubMed  CAS  Google Scholar 

  • Odoardi F, Sie C, Streyl K, Ulaganathan VK, Schläger C, Lodygin D, Heckelsmiller K, Nietfeld W, Ellwart J, Klinkert WE, Lottaz C, Nosov M, Brinkmann V, Spang R, Lehrach H, Vingron M, Wekerle H, Flügel-Koch C, Flügel A (2012) T cells become licensed in the lung to enter the central nervous system. Nature 488:675–679

    Article  PubMed  CAS  Google Scholar 

  • Ohno K, Pettigrew KD, Rapoport SI (1978) Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat. Am J Physiol 235:299–307

    Google Scholar 

  • Paik JH, Skoura A, Chae SS, Cowan AE, Han DK, Proia RL, Hla T (2004) Sphingosine-1-phosphate receptor regulation on N-cadherin mediates vascular stabilization. Genes Dev 18:2392–2403

    Article  PubMed  CAS  Google Scholar 

  • Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD (2006) Blood-brain barrier: structural components and function under physiologic and pathologic conditions. J NeuroImmune Pharmacol 1:223–236

    Article  PubMed  Google Scholar 

  • Price DL, Ludwig JW, Mi H, Schwarz TL, Ellisman MH (2002) Distribution of rSlo Ca2+-activated K+ channels in rat astrocyte perivascular endfeet. Brain Res 956:183–193

    Article  PubMed  CAS  Google Scholar 

  • Rao R (2009) Occludin phosphorylation in regulation of epithelial tight junctions. Ann N Y Acad Sci 1165:62–68

    Article  PubMed  CAS  Google Scholar 

  • Reese TS, Karnovsky MJ (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34:207–217

    Article  PubMed  CAS  Google Scholar 

  • Roberts LM, Black DS, Raman C, Woodford K, Zhou M, Haggerty JE, Yan AT, Cwirla SE, Grindstaff KK (2008) Subcellular localization of transporters along the rat blood-brain barrier and blood-cerebral-spinal fluid barrier by in vivo biotinylation. Neuroscience 155:423–438

    Article  PubMed  CAS  Google Scholar 

  • Saitou M, Furuse M, Sasaki H, Schulzke JD, Fromm M, Takano H, Noda T, Tsukita S (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11(12):4131–4142

    Article  PubMed  CAS  Google Scholar 

  • Sakakibara A, Furuse M, Saitou M, Ando-Akatsuka Y, Tsukita S (1997) Possible involvement of phosphorylation of occludin in tight junction formation. J Cell Biol 137:1393–1401

    Article  PubMed  CAS  Google Scholar 

  • Shimizu F, Sano Y, Maeda T, Abe MA, Nakayama H, Takahashi R, Ueda M, Ohtsuki S, Terasaki T, Obinata M, Kanda T (2008) Peripheral nerve pericytes originating from the blood–nerve barrier expresses tight junctional molecules and transporters as barrier-forming cells. J Cell Physiol 217:388–399

    Article  PubMed  CAS  Google Scholar 

  • Shin K, Margolis B (2006) Zoning out tight junctions. Cell 126:647–649

    Article  PubMed  CAS  Google Scholar 

  • Sixt M, Engelhardt B, Pausch F, Hallmann R, Wendler O, Sorokin LM (2001) Endothelial cell laminin isoforms, laminins 8 and 10, play decisive roles in T cell recruitment across the blood-brain barrier in experimental autoimmune encephalomyelitis. J Cell Biol 153:933–946

    Article  PubMed  CAS  Google Scholar 

  • Sorokin L (2010) The impact of the extracellular matrix on inflammation. Nat Rev Immunol 10:712–723

    Article  PubMed  CAS  Google Scholar 

  • Stevenson BR, Siliciano JD, Mooseker MS, Goodenough DA (1986) Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J Cell Biol 103:755–766

    Article  PubMed  CAS  Google Scholar 

  • Stewart PA, Wiley MJ (1981) Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: a study using quail-chick transplantation chimeras. Dev Biol 84:183–192

    Article  PubMed  CAS  Google Scholar 

  • Toft-Hansen H, Buist R, Sun XJ, Schellenberg A, Peeling J, Owens T (2006) Metalloproteinases control brain inflammation induced by pertussis toxin in mice overexpressing the chemokine CCL2 in the central nervous system. J Immunol 177:7242–7249

    PubMed  CAS  Google Scholar 

  • Toyofuku T, Yabuki M, Otsu K, Kuzuya T, Hori M, Tada M (1998) Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes. J Biol Chem 273:12725–12731

    Article  PubMed  CAS  Google Scholar 

  • Umeda K, Matsui T, Nakayama M, Furuse K, Sasaki H, Furuse M, Tsukita S (2004) Establishment and characterization of cultured epithelial cells lacking expression of ZO-1. J Biol Chem 279:44785–44794

    Article  PubMed  CAS  Google Scholar 

  • Verkman AS (2002) Aquaporin water channels and endothelial cell function. J Anat 200:617–627

    Article  PubMed  CAS  Google Scholar 

  • Winkler EA, Bell RD, Zlokovic BV (2011) Central nervous system pericytes in health and disease. Nat Neurosci 14:1398–1405

    Article  PubMed  CAS  Google Scholar 

  • Wolburg H, Lippoldt A (2002) Tight junctions of the blood-brain barrier: development, composition and regulation. Vasc Pharmacol 38:323–337

    Article  CAS  Google Scholar 

  • Wolburg H, Noell S, Mack A, Wolburg-Buchholz K, Fallier-Becker P (2009) Brain endothelial cells and the glio–vascular complex. Cell Tissue Res 335:75–96

    Article  PubMed  Google Scholar 

  • Wu C, Ivars F, Anderson P, Hallmann R, Vestweber D, Nilsson P, Robenek H, Tryggvason K, Song J, Korpos E, Loser K, Beissert S, Georges-Labouesse E, Sorokin LM (2009) Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte extravasation into the brain. Nat Med 15:519–527

    Article  PubMed  CAS  Google Scholar 

  • Zlokovic BV (2008) The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron 57:178–201

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Our studies on the BBB are supported by the DFG (FOR1336).

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The authors declare that they have no conflict of interest.

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Correspondence to Ingo Bechmann.

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Dyrna, F., Hanske, S., Krueger, M. et al. The Blood-Brain Barrier. J Neuroimmune Pharmacol 8, 763–773 (2013). https://doi.org/10.1007/s11481-013-9473-5

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