Skip to main content
SpringerLink
Log in

Blood–Brain Barrier Models

  • Reference work entry
  • First Online:
Handbook of Neurochemistry and Molecular Neurobiology

Abstract:

In the last 25 years, a great number of cell culture–based blood–brain barrier (BBB) models have been developed. First, primary cultures and passages of cerebral endothelial cells were used as monolayers for experiments. Later, immortalized cell lines have been established and used as BBB models. As brain endothelial cells lose easily their specific characteristics in culture, and the importance of signals from the cells of the neurovascular unit in the induction of BBB properties has been recognized, in the next stage of BBB modeling monocultures were replaced by coculture systems using glial cells, neurons, or pericytes. These models are valuable tools to study cell–cell interaction in the neurovascular unit, modulation of BBB permeability in physiological, pathological, and pharmacological conditions. Some of the BBB models can serve as permeability screens for the pharmaceutical industry.

This chapter will summarize the most frequently used types of in vitro BBB models of bovine, human, porcine, and rodent origin, and their main applications.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 249.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

1400W:

N-(3-aminomethyl)benzylacetamidine

Ac-LDL:

acetylated low-density lipoprotein

ACE:

angiotensin converting enzyme

ALP:

alkaline phosphatase

ASCT2:

sodium-dependent neutral amino acid transporter type 2

ATA2:

amino acid transporter A2

BBB:

blood-brain barrier

BCRP:

brain multidrug resistance protein

CNS:

central nervous system

CNT-2:

sodium-coupled nucleoside transporter

COMT:

catechol-ortho-methyl-transferase

CRT:

creatine transporter

cyclic AMP:

adenosine 3′,5′-cyclic monophosphate

cyclic GMP:

guanosine 3′,5′-cyclic monophosphate

DETA-NONOate:

2,2′-(Hydroxynitrosohydrazino)bis-ethanamine

DPPE:

N,N-diethyl-2-[4-(phenylmethyl)-phenoxy]ethanamine

EAAT:

excitatory amino acid transporter

ECE-1:

endothelin converting enzyme-1

eNOS:

endothelial nitric oxide synthase

EVOM:

epithelial Volt-Ohm meter

FGF1:

acidic fibroblast growth factor

FGF2:

basic fibroblast growth factor

GAT2:

GABA transporter 2 (same as BGT1)

γ-GT:

γ-glutamyl-transpeptidase

GDNF:

glial cell line-derived neurotrophic factor

GLUT-1:

glucose transporter-1

gp120:

120 kDa glycoprotein

HIV-1:

human immunodeficiency virus-1

HTLV-1:

human T-cell leukemia virus type-1

JAM:

junctional adhesion molecule

LAT-1:

large neutral amino-acid transporter-1

LDL:

low density lipoprotein

L-NAME:

N ω-nitro-l-arginine methyl ester

LPS:

lipopolysaccharide

LRP:

low-density lipoprotein-related receptor

MAO A and B:

monoamine oxidase A and B

MCT-1:

monocarboxylic acid transporter

MK-801:

dizocilpine

MRP:

multidrug resistance protein

neuroAIDS:

neurological symptoms of acquired immunodeficiency syndrome

NET:

norepinephrine transporter

NMDA:

N-methyl-d-aspartic acid

NO:

nitric oxide

OAT3:

organic anion transporter 3

OATP2:

organic anion-transporting polypeptide 2

OGD:

oxygen-glucose deprivation

P e :

endothelial permeability coefficient

PECAM-1:

platelet-endothelial cell adhesion molecule-1

PLA2:

phospholipase A2

RAGE:

receptor for advanced glycation end-products

SERT:

serotonin transporter

SKF 96365:

1-[2-(4-Methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole hydrochloride

TAUT:

taurin transporter

TEER:

transendothelial electrical resistance

TGF-β:

transforming growth factor-β

TJ:

tight junctions

U83836E:

(-)-2-((4-(2,6-Di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl)methyl)-3,4-dihydro-2,3,7,8-tetramethyl-2H-1-benzopyran-6-ol, 2HCl

UGT:

UDP-glucoronyl-transferase

VCAM-1:

vascular cell adhesion molecule-1

VEGF:

vascular endothelial cell growth factor

ZO-1, -2:

zonula occludens protein 1 and 2

References

  • Abbott NJ. 2000. Inflammatory mediators and modulation of blood-brain barrier permeability. Cell Mol Neurobiol 20: 131–147.

    Article  CAS  PubMed  Google Scholar 

  • Abbott NJ. 2002. Astrocyte-endothelial interactions and the blood-brain barrier permeability. J Anat 200: 629–638.

    Article  CAS  PubMed  Google Scholar 

  • Abbott NJ. 2005. Dynamics of CNS barriers: Evolution, differentiation and modulation. Cell Mol Neurobiol 25: 5–23.

    Article  PubMed  Google Scholar 

  • Abbott NJ, Hughes CCW, Revest PA, Greenwood J. 1992. Development and characterisation of a rat brain capillary endothelial culture: Towards an in vitro blood-brain barrier. J Cell Sci 103: 23–37.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Abulrob A, Sprong H, Van Bergen en Henegouwen P, Stanimirovic D. 2005. The blood-brain barrier transmigrating single domain antibody: Mechanisms of transport and antigenic epitopes in human brain endothelial cells. J Neurochem 95: 1201–1214.

    Article  CAS  PubMed  Google Scholar 

  • Alt C, Duvefelt K, Franzen B, Yang Y, Engelhardt B. 2005. Gene and protein expression profiling of the microvascular compartment in experimental autoimmune encephalomyelitis in C57Bl/6 and SJL mice. Brain Pathol 15: 1–16.

    Article  CAS  PubMed  Google Scholar 

  • Annunziata P, Cioni C, Santonini R, Paccagnini E. 2002. Substance P antagonist blocks leakage and reduces activation of cytokine-stimulated rat brain endothelium. J Neuroimmunol 131: 41–49.

    Article  CAS  PubMed  Google Scholar 

  • Annunziata P, Cioni C, Toneatto S, Paccagnini E. 1998. HIV-1 gp120 increases the permeability of rat brain endothelium cultures by a mechanism involving substance P. AIDS 12: 2377–2385.

    Article  CAS  PubMed  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.

    CAS  PubMed  Google Scholar 

  • Badger JL, Stins MF, Kim KS. 1999. Citrobacter freundii invades and replicates in human brain microvascular endothelial cells. Infect Immun 67: 4208–4215.

    CAS  PubMed  Google Scholar 

  • Banks WA. 1999. Physiology and pathology of the blood-brain barrier: Implications for microbial pathogenesis, drug delivery and neurodegenerative disorders. J Neurovirol 5: 538–555.

    Article  CAS  PubMed  Google Scholar 

  • Batrakova EV, Li S, Vinogradov SV, Alakhov VY, Miller DW, et al. 2001a. Mechanism of pluronic effect on P-glycoprotein efflux system in blood-brain barrier: Contributions of energy depletion and membrane fluidization. J Pharmacol Exp Ther 299: 483–493.

    CAS  Google Scholar 

  • Batrakova EV, Miller DW, Li S, Alakhov VY, Kabanov AV, et al. 2001b. Pluronic P85 enhances the delivery of digoxin to the brain: In vitro and in vivo studies. J Pharmacol Exp Ther 296: 551–557.

    CAS  Google Scholar 

  • Bauer HC, Bauer H. 2000. Neural induction of the blood-brain barrier: Still an enigma. Cell Mol Neurobiol 20: 13–28.

    Article  CAS  PubMed  Google Scholar 

  • Berezowski V, Landry C, Dehouck M-P, Cecchelli R, Fenart L. 2004. Contribution of glial cells and pericytes to the mRNA profiles of P-glycoprotein and multidrug resistance-associated proteins in an in vitro model of the blood-brain barrier. Brain Res 1018: 1–9.

    Article  CAS  PubMed  Google Scholar 

  • Boveri M, Berezowski V, Price A, Slupek S, Lenfant AM, et al. 2005. Induction of blood-brain barrier properties in cultured brain capillary endothelial cells: Comparison between primary glial cells and C6 cell line. Glia 51: 187–198.

    Article  PubMed  Google Scholar 

  • Boveri M, Kinsner A, Berezowski V, Lenfant AM, Draing C, et al. 2006. Highly purified lipoteichoic acid from gram-positive bacteria induces in vitro blood-brain barrier disruption through glia activation: Role of pro-inflammatory cytokines and nitric oxide. Neuroscience 137: 1193–1209.

    Article  CAS  PubMed  Google Scholar 

  • Bowman PD, Betz AL, Wolinsky JS, Penny JB, Shivers RR, et al. 1981. Primary cultures of capillary endothelium from rat brain. In Vitro 17: 353–362.

    Article  CAS  PubMed  Google Scholar 

  • Bowman PD, Ennis SR, Rarey KE, Betz AL, Goldstein GW. 1983. Brain microvessel endothelial cells in tissue culture: A model for study of blood-brain barrier permeability. Ann Neurol 14: 396–402.

    Article  CAS  PubMed  Google Scholar 

  • Brightman MW, Reese TS. 1969. Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol 40: 648–677.

    Article  CAS  PubMed  Google Scholar 

  • Brillault J, Berezowski V, Cecchelli R, 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  CAS  PubMed  Google Scholar 

  • Brown J, Reading SJ, Jones S, Fitchett CJ, Howl J, et al. 2000. Critical evaluation of ECV304 as a human endothelial cell model defined by genetic analysis and functional responses: A comparison with the human bladder cancer derived epithelial cell line T24/83. Lab Invest 80: 37–45.

    Article  CAS  PubMed  Google Scholar 

  • Brown RC, Mark KS, Egleton RD, Huber JD, Burroughs AR, et al. 2003. Protection against hypoxia-induced increase in blood-brain barrier permeability: Role of tight junction proteins and NFκB. J Cell Sci 116: 693–700.

    Article  CAS  PubMed  Google Scholar 

  • Brückener KE, el Bayâ A, Galla H-J, Schmidt MA. 2003. Permeabilization in a cerebral endothelial barrier model by pertussis toxin involves the PKC effector pathway and is abolished by elevated levels of cAMP. J Cell Sci 116: 1837–1846.

    Article  PubMed  CAS  Google Scholar 

  • Cecchelli R, Dehouck B, Descamps L, Fenart L, Buée-Scherrer V, et al. 1999. In vitro model for evaluating drug transport across the blood-brain barrier. Adv Drug Deliv Rev 36: 165–178.

    Article  CAS  PubMed  Google Scholar 

  • Cestelli A, Catania C, D'Agostino S, Di Liegro I, Licata L, et al. 2001. Functional feature of a novel model of blood brain barrier: Studies on permeation of test compounds. J Control Release 76: 139–147.

    Article  CAS  PubMed  Google Scholar 

  • Chen L, Kis B, Busija DW, Yamashita H, Ueta Y. 2005. Adrenomedullin protects rat cerebral endothelial cells from oxidant damage in vitro. Regul Pept 130: 27–34.

    Article  CAS  PubMed  Google Scholar 

  • Chishty M, Reichel A, Siva J, Abbott NJ, Begley DJ. 2001. Affinity for the P-glycoprotein efflux pump at the blood-brain barrier may explain the lack of CNS side-effects of modern antihistamines. J Drug Target 9: 223–228.

    Article  CAS  PubMed  Google Scholar 

  • Chopineau J, Robert S, Fenart L, Cecchelli R, Lagoutte B, et al. 1998. Monoacylation of ribonuclease A enables its transport across an in vitro model of the blood-brain barrier. J Control Release 56: 231–237.

    Article  CAS  PubMed  Google Scholar 

  • Coisne C, Dehouck L, Faveeuw C, Delplace Y, Miller F, et al. 2005. Mouse syngenic in vitro blood-brain barrier model: A new tool to examine inflammatory events in cerebral endothelium. Lab Invest 85: 734–746.

    Article  CAS  PubMed  Google Scholar 

  • Cucullo L, Hallene K, Dini G, Dal Toso R, Janigro D. 2004. Glycerophosphoinositol and dexamethasone improve transendothelial electrical resistance in an in vitro study of the blood-brain barrier. Brain Res 997: 147–151.

    Article  CAS  PubMed  Google Scholar 

  • de Boer AG, van der Sandt ICJ, Gaillard PJ. 2003. The role of drug transporters at the blood-brain barrier. Annu Rev Pharmacol Toxicol 43: 629–656.

    Article  CAS  PubMed  Google Scholar 

  • de Vries HE, Blom-Roosemalen MC, de Boer AG, van Berkel TJ, Breimer DD, et al. 1996a. Effect of endotoxin on permeability of bovine cerebral endothelial cell layers in vitro. J Pharmacol Exp Ther 277: 1418–1423.

    CAS  Google Scholar 

  • de Vries HE, Blom-Roosemalen MC, van Oosten M, de Boer AG, van Berkel TJ, et al. 1996b. The influence of cytokines on the integrity of the blood-brain barrier in vitro. J Neuroimmunol 64: 37–43.

    Article  CAS  Google Scholar 

  • De Bault LE, Cancilla PA. 1980. Gamma-glutamyl transpeptidase in isolated brain endothelial cells: Induction by glial cells in vitro. Science 207: 653–655.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Dehouck M-P, Méresse S, Dehouck B, Fruchart JC, Cecchelli R. 1992. In vitro reconstituted blood-brain barrier. J Control Release 21: 81–92.

    Article  CAS  Google Scholar 

  • Deli MA. 2005. The role of blood-brain barrier in neurodegenerative diseases. Molecular Bases of Neurodegeneration. Di Liegro I, Savettieri G, editors. Kerala, India: Research Signpost; pp. 137–161.

    Google Scholar 

  • Deli MA, Ábrahám CS, Kataoka Y, Niwa M. 2005. Permeability studies on in vitro blood-brain barrier models: Physiology, pathology, and pharmacology. Cell Mol Neurobiol 25: 59–127.

    Article  PubMed  Google Scholar 

  • Deli MA, Ábrahám CS, Niwa M, Falus A. 2003. N,N-diethyl-2-[4-(phenylmethyl)phenoxy]-ethanamide increases the permeability of primary mouse cerebral endothelial cell monolayers. Inflamm Res 52: S39–S40.

    Article  CAS  PubMed  Google Scholar 

  • Deli MA, Dehouck M-P, Ábrahám CS, Cecchelli R, Joó F. 1995a. Penetration of small molecular weight substances through cultured bovine brain capillary endothelial cells: The early effects of 3′,5′-cyclic adenosine monophosphate. Exp Physiol 80: 675–678.

    CAS  Google Scholar 

  • Deli MA, Dehouck M-P, Cecchelli R, Ábrahám CS, Joó F. 1995b. Histamine induces a selective albumin permeation through the blood-brain barrier in vitro. Inflamm Res 44: S56–S57.

    Article  CAS  Google Scholar 

  • Deli MA, Descamps L, Dehouck M-P, Cecchelli R, Joó F, et al. 1995c. Exposure of tumor necrosis factor α to the luminal membrane induces a delayed increase of permeability and formation of cytoplasmic actin stress fibers in brain capillary endothelial cells cocultured with astrocytes. J Neurosci Res 41: 717–726.

    Article  CAS  Google Scholar 

  • Deli MA, Sakaguchi S, Nakaoke R, Ábrahám CS, Takahata H, et al. 2000. PrP fragment 106–126 is toxic to cerebral endothelial cells expressing PrP(C). Neuroreport 11: 3931–3936.

    Article  CAS  PubMed  Google Scholar 

  • Descamps L, Cecchelli R, Torpier G. 1997. Effects of tumor necrosis factor on receptor-mediated endocytosis and barrier functions of bovine brain capillary endothelial cell monolayers. J Neuroimmunol 74: 173–184.

    Article  CAS  PubMed  Google Scholar 

  • Descamps L, Coisne C, Dehouck B, Cecchelli R, Torpier G. 2003. Protective effect of glial cells against lipopolysaccharide-mediated blood-brain barrier injury. Glia 42: 46–58.

    Article  PubMed  Google Scholar 

  • Diaz CM, Penfold PL, Provis JM. 1998. Modulation of the resistance of a human endothelial cell line by human retinal glia. Aust N Z J Ophthalmol 26: S62–S64.

    Article  PubMed  Google Scholar 

  • Dobbie MS, Hurst RD, Klein NJ, Surtees RAH. 1999. Upregulation of intracellular adhesion molecule-1 expression on human endothelial cells by tumour necrosis factor-α in an in vitro model of the blood-brain barrier. Brain Res 830: 330–336.

    Article  CAS  PubMed  Google Scholar 

  • Dohgu S, Takata F, Yamauchi A, Nakagawa S, Egawa T, et al. 2005. Brain pericytes contribute to the induction and up-regulation of blood-brain barrier functions through transforming growth factor-beta production. Brain Res 1038: 208–215.

    Article  CAS  PubMed  Google Scholar 

  • Doolittle ND, Abrey LE, Bleyer WA, Brem S, Davis TP, et al. 2005. New frontiers in translational research in neuro-oncology and the blood-brain barrier: Report of the tenth annual Blood-Brain Barrier Disruption Consortium Meeting. Clin Cancer Res 11: 421–428.

    PubMed  Google Scholar 

  • Doolittle ND, Miner ME, Hall WA, Siegal T, Jerome E, et al. 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 tumors. Cancer 88: 637–647.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Dömötör E, Sipos I, Kittel A, Abbott NJ, Ádám-Vízi V. 1998. Improved growth of cultured brain microvascular endothelial cells on glass coated with a biological matrix. Neurochem Int 33: 473–478.

    Article  PubMed  Google Scholar 

  • Easton AS, Abbott JN. 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.

    Article  CAS  PubMed  Google Scholar 

  • El Hafny B, Bourre JM, 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  CAS  PubMed  Google Scholar 

  • Enerson BE, Drewes LR. 2006. The rat blood-brain barrier transcriptome. J Cereb Blood Flow Metab 26: 959–973.

    Article  CAS  PubMed  Google Scholar 

  • Farkas A, Szatmári E, Orbók A, Wilhelm I, Wejksza K, et al. 2005. Hyperosmotic mannitol induces Src kinase-dependent phosphorylation of beta-catenin in cerebral endothelial cells. J Neurosci Res 80: 855–861.

    Article  CAS  PubMed  Google Scholar 

  • Fenart L, Casanova A, Dehouck B, Duhem C, Slupek S, et al. 1999. Evaluation of effect of charge and lipid coating on ability of 60-nm nanoparticles to cross an in vitro model of the blood-brain barrier. J Pharmacol Exp Ther 291: 1017–1022.

    CAS  PubMed  Google Scholar 

  • Fillebeen C, Dehouck B, Benaïssa M, Dhennin-Duthille I, Cecchelli R, et al. 1999. Tumor necrosis factor-α increases lactoferrin transcytosis through the blood-brain barrier. J Neurochem 73: 2491–2500.

    Article  CAS  PubMed  Google Scholar 

  • Fischer S, Clauss M, Wiesnet M, Renz D, Schaper W, et al. 1999. Hypoxia induces permeability in brain microvessel endothelial cells via VEGF and NO. Am J Physiol Cell Physiol 276: C812–C820.

    CAS  Google Scholar 

  • Fischer S, Renz D, Schaper W, Karliczek GF. 1995. In vitro effects of fentanyl, methohexital, and thiopental brain endothelial permeability. Anesthesiology 82: 451–458.

    Article  CAS  PubMed  Google Scholar 

  • Fischer S, Renz D, Schaper W, Karliczek GF. 2001. In vitro effects of dexamethasone on hypoxia-induced hyperpermeability and expression of vascular endothelial growth factor. Eur J Pharmacol 411: 231–243.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Franzen B, Duvefelt K, Jonsson C, Engelhardt B, Ottervald J, et al. 2003. Gene and protein expression profiling of human cerebral endothelial cells activated with tumor necrosis factor-alpha. Brain Res Mol Brain Res 115: 130–146.

    Article  CAS  PubMed  Google Scholar 

  • Gaillard PJ, de Boer AB, Breimer DD. 2003. Pharmacological investigations on lipopolysaccharide-induced permeability changes in the blood-brain barrier in vitro. Microvasc Res 65: 24–31.

    Article  CAS  PubMed  Google Scholar 

  • Gaillard PJ, de Boer AG. 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.

    Article  CAS  PubMed  Google Scholar 

  • Garberg P, Ball M, Borg N, Cecchelli R, Fenart L, et al. 2005. In vitro models for the blood-brain barrier. Toxicol. In Vitro 19: 299–334.

    Article  CAS  PubMed  Google Scholar 

  • Garcia CM, Darland DC, Massingham LJ, D'Amore PA. 2004. Endothelial cell-astrocyte interactions and TGF beta are required for induction of blood-neural barrier properties. Brain Res Dev Brain Res 152: 25–38.

    Article  CAS  PubMed  Google Scholar 

  • Ge S, Song L, Pachter JS. 2005. Where is the blood-brain barrier … really? J Neurosci Res 79: 421–427.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Girod J, Fenart L, Regina A, Dehouck M-P, Hong G, et al. 1999. Transport of cationized anti-tetanus Fab'2 fragments across an in vitro blood-brain barrier model: Involvement of the transcytosis pathway. J Neurochem 73: 2002–2008.

    CAS  PubMed  Google Scholar 

  • Gloor SM, Weber A, Adachi N, Frei K. 1997. Interleukin-1 modulates protein tyrosine phosphatase activity and permeability of brain endothelial cells. Biochem Biophys Res Commun 239: 804–809.

    Article  CAS  PubMed  Google Scholar 

  • Grabb PA, Gilbert MR. 1995. Neoplastic and pharmacological influence on the permeability of an in vitro blood-brain barrier. J Neurosurg 82: 1053–1058.

    Article  CAS  PubMed  Google Scholar 

  • Greenwood J, Pryce G, Devine L, Male DK, dos Santos WL, et al. 1996. SV40 large immortalised cell lines of the rat blood-brain and blood-retinal barriers retain their phenotypic and immunological characteristics. J Neuroimmunol 71: 51–63.

    Article  CAS  PubMed  Google Scholar 

  • Gumbleton M, Audus KL. 2001. Progress and limitations in the use of in vitro cell cultures to serve as a permeability screen for the blood-brain barrier. J Pharm Sci 90: 1681–1698.

    Article  CAS  PubMed  Google Scholar 

  • Hamm S, Dehouck B, Kraus J, Wolburg-Buchholz K, Wolburg H, et al. 2004. Astrocyte mediated modulation of blood-brain barrier permeability does not correlate with a loss of tight junction proteins from the cellular contacts. Cell Tissue Res 315: 157–166.

    Article  PubMed  Google Scholar 

  • Hart MN, Van Dyk LF, Moore SA, Shasby DM, Cancilla PA. 1987. Differential opening of the brain endothelial barrier following neutralization of the endothelial luminal anionic charge in vitro. J Neuropathol Exp Neurol 46: 141–153.

    Article  CAS  PubMed  Google Scholar 

  • Haseloff RF, Blasig IE, Bauer H-C, Bauer H. 2005. 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.

    Article  CAS  PubMed  Google Scholar 

  • Haseloff RF, Krause E, Bigl M, Mikoteit K, Stanimirovic D, et al. 2006. Differential protein expression in brain capillary endothelial cells induced by hypoxia and posthypoxic reoxygenation. Proteomics 6: 1803–1809.

    Article  CAS  PubMed  Google Scholar 

  • Hayashi K, Nakao S, Nakaoke R, Nakagawa, S., Kitagawa, N., et al. 2004. Effects of hypoxia on endothelial/pericytic co-culture model of the blood-brain barrier. Regul Pept 123: 77–83.

    Article  CAS  PubMed  Google Scholar 

  • Hoheisel D, Nitz T, Franke H, Wegener J, Hakvoort A, et al. 1998. Hydroocortisone reinforces the blood-brain barrier properties in a serum free cell culture system. Biochem Biophys Res Commun 247: 312–315.

    Article  CAS  PubMed  Google Scholar 

  • Hori S, Ohtsuki S, Hosoya K, Nakashima E, Terasaki T. 2004. A pericyte-derived angiopoietin-1 multimeric complex induces occludin gene expression in brain capillary endothelial cells through Tie-2 activation in vitro. J Neurochem 89: 503–513.

    Article  CAS  PubMed  Google Scholar 

  • Hosoya K, Tetsuka K, Nagase K, Tomi M, Saeki S, et al. 2000. Conditionally immortalized brain capillary endothelial cell lines established from a transgenic mouse harboring temperature-sensitive simian virus 40 large T-antigen gene. AAPS Pharmsci 2(3): E27, pp. 1–11. [http://www.pharmsci.org]

  • Hudson LC, Bragg DC, Tompkins MB, Meeker RB. 2005. Astrocytes and microglia differentially regulate trafficking of lymphocyte subsets across brain endothelial cells. Brain Res 1058: 148–160.

    Article  CAS  PubMed  Google Scholar 

  • Hurst RD, Clark JB. 1997. Nitric oxide-induced blood-brain barrier dysfunction is not mediated by inhibition of mitochondrial respiratory chain activity and/or energy depletion. Nitric Oxide 1: 121–129.

    Article  CAS  PubMed  Google Scholar 

  • Hurst RD, Clark JB. 1998. Alterations in transendothelial electrical resistance by vasoactive agonists and cyclic AMP in a blood-brain barrier model system. Neurochem Res 23: 149–154.

    Article  CAS  PubMed  Google Scholar 

  • Hurst RD, Clark JB. 1999. Butyric acid mediated induction of enhanced transendothelial resistance in an in vitro model blood-brain barrier system. Neurochem Int 35: 261–267.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Hurst RD, Heales SJR, Dobbie MS, Barker JE, Clark JB. 1998. Decreased endothelial cell glutathione and increased sensitivity to oxidative stress in an in vitro blood-brain barrier model system. Brain Res 802: 232–240.

    Article  CAS  PubMed  Google Scholar 

  • Igarashi Y, Utsumi H, Chiba H, Yamada-Sasamori Y, Tobioka H, et al. 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  CAS  PubMed  Google Scholar 

  • Jong AY, Stins MF, Huang S-H, Chen SHM, Kim KS. 2001. Traversal of Candida albicans across human blood-brain barrier in vitro. Infect Immun 69: 4536–4544.

    Article  CAS  PubMed  Google Scholar 

  • Joó F. 1985. The blood-brain barrier in vitro: Ten years of research on microvessels isolated from the brain. Neurochem Int 7: 1–25.

    Article  PubMed  Google Scholar 

  • Joó F. 1992. The cerebral microvessels in culture, an update. J Neurochem 58: 1–17.

    Article  PubMed  Google Scholar 

  • Joó F. 1993. The blood-brain barrier in vitro: The second decade. Neurochem Int 23: 499–521.

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Kása P, Pákáski M, Joó F, Lajtha A. 1991. Endothelial cells from human fetal brain microvessels may be cholinoceptive, but do not synthesize acetylcholine. J Neurochem 56: 2143–2146.

    Article  PubMed  Google Scholar 

  • Kiessling F, Kartenbeck J, 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  PubMed  Google Scholar 

  • Kim JA, Tran ND, Li Z, Yang F, Zhou W, et al. 2006. Brain endothelial hemostasis regulation by pericytes. J Cereb Blood Flow Metab 26: 209–217.

    Article  PubMed  CAS  Google Scholar 

  • Kis B, Deli MA, Kobayashi H, Ábrahám CS, Yanagita T, et al. 2001. Adrenomedullin regulates blood-brain barrier functions in vitro. Neuroreport 12: 4139–4142.

    Article  CAS  PubMed  Google Scholar 

  • Kondo T, Kinouchi H, Kawase M, Yoshimoto T. 1996. Astroglial cells inhibit the increasing permeability of brain endothelial cell monolayer following hypoxia/reoxygenation. Neurosci Lett 208: 101–104.

    Article  CAS  PubMed  Google Scholar 

  • Krizanac-Bengez L, Kapural M, Parkinson F, Cucullo L, Hossain M, et al. 2003. Effects of transient loss of shear stress on blood-brain barrier endothelium: Role of nitric oxide and IL-6. Brain Res 977: 239–246.

    Article  CAS  PubMed  Google Scholar 

  • Krizanac-Bengez L, Mayberg MR, Cunningham E, Hossain M, Ponnampalam S, et al. 2006. Loss of shear stress induces leukocyte-mediated cytokine release and blood-brain barrier failure in dynamic in vitro blood-brain barrier model. J Cell Physiol 206: 68–77.

    Article  CAS  PubMed  Google Scholar 

  • Krizbai IA, Deli MA. 2003. Signalling pathways regulating the tight junction permeability in the blood-brain barrier. Cell Mol Biol (Noisy-le-grand) 49: 23–31.

    CAS  Google Scholar 

  • Kusch-Poddar M, Drewe J, Fux I, Gutmann H. 2005. Evaluation of the immortalized human brain capillary endothelial cell line BB19 as a human cell culture model for the blood-brain barrier. Brain Res 1064: 21–31.

    Article  CAS  PubMed  Google Scholar 

  • Kusuhara H, Sugiyama Y. 2001a. Efflux transport systems for drugs at the blood-brain barrier and blood-cerebrospinal fluid barrier (Part 1). Drug Discov Today 6: 150–156.

    Article  CAS  Google Scholar 

  • Kusuhara H, Sugiyama Y. 2001b. Efflux transport systems for drugs at the blood-brain barrier and blood-cerebrospinal fluid barrier (Part 2). Drug Discov Today 6: 206–212.

    Article  CAS  Google Scholar 

  • Kusuhara H, Suzuki H, Naito M, Tsuruo T, Sugiyama Y. 1998. Characterization of efflux transport of organic anions in a mouse brain capillary endothelial cell line. J Pharmacol Exp Ther 285: 1260–1265.

    CAS  PubMed  Google Scholar 

  • Lee S-W, Kim WJ, Choi YK, SongHS, Son M. J., et al. 2003. SSeCKS regulates angiogenesis and tight junction formation in blood-brain barrier. Nat Med 9: 900–906.

    Article  CAS  PubMed  Google Scholar 

  • Liu NQ, Lossinsky AS, Popik W, Li X, Gujuluva C, et al. 2002. Human immunodeficiency virus type 1 enters brain microvascular endothelia by macropinocytosis dependent on lipid rafts and the mitogen-activated protein kinase signaling pathway. J Virol 76: 6689–6700.

    Article  CAS  PubMed  Google Scholar 

  • Lundquist S, Renftel M, Brillault J, Fenart L, Cecchelli R, et al. 2002. Prediction of drug transport through the blood-brain barrier in vivo: A comparison between two in vitro cell models. Pharm Res 19: 976–981.

    Article  CAS  PubMed  Google Scholar 

  • Mackic JB, Stins M, Jovanovic S, Kim KS, Bartus RT, et al. 1999. Cereport (RMP-7) increases the permeability of human brain microvascular endothelial cell monolayers. Pharm Res 16: 1360–1365.

    Article  CAS  PubMed  Google Scholar 

  • Mark KS, Burroughs AR, Brown RC, Huber JD, Davis TP. 2004. Nitric oxide mediates hypoxia-induced changes in paracellular permeability of cerebral microvasculature. Am J Physiol Heart Circ Physiol 286: H174–H180.

    Article  CAS  PubMed  Google Scholar 

  • Mathieu C, Fouchet P, Gauthier LR, Lassalle B, Boussin FD, et al. 2006. Coculture with endothelial cells reduces the population of cycling LeX neural precursors but increases that of quiescent cells with a side population phenotype. Exp Cell Res 312: 707–718.

    Article  CAS  PubMed  Google Scholar 

  • Miller F, Fenart L, Landry V, Coisne C, Cecchelli R, et al. 2005. The MAP kinase pathway mediates transcytosis induced by TNF-alpha in an in vitro blood-brain barrier model. Eur J Neurosci 22: 835–844.

    Article  PubMed  Google Scholar 

  • Muruganandam A, Tanha J, Narang S, Stanimirovic D. 2002. Selection of phage-displayed llama single-domain antibodies that transmigrate across human blood-brain barrier endothelium. FASEB J 16: 240–242.

    CAS  PubMed  Google Scholar 

  • Nakaoke R, Ryerse JS, Niwa M, Banks WA. 2005. Human immunodeficiency virus type 1 transport across the in vitro mouse brain endothelial cell monolayer. Exp Neurol 193: 101–109.

    Article  PubMed  Google Scholar 

  • Neuwelt EA, Rapoport SI. 1984. Modification of the blood-brain barrier in the chemotherapy of malignant brain tumors. Fed Proc 43: 214–219.

    CAS  PubMed  Google Scholar 

  • Nitz T, Eisenblatter T, Psathaki K, Galla H-J. 2003. Serum-derived factors weaken the barrier properties of cultured porcine brain capillary endothelial cells in vitro. Brain Res 981: 30–40.

    Article  CAS  PubMed  Google Scholar 

  • Omidi Y, Campbell L, Barar J, Connell D, Akhtar S, et al. 2003. Evaluation of the immortalised mouse brain capillary endothelial cell line, b.End3, as an in vitro blood-brain barrier model for drug uptake and transport studies. Brain Res 990: 95–122.

    Article  CAS  PubMed  Google Scholar 

  • Panula P, Joó F, Rechardt L. 1978. Evidence for the presence of viable endothelial cells in cultures derived from dissociated rat brain. Experientia 34: 95–97.

    Article  CAS  PubMed  Google Scholar 

  • Pardridge WM. 2002. Drug and gene targeting to brain with molecular Trojan horses. Nat Rev Drug Discov 1: 131–139.

    Article  CAS  PubMed  Google Scholar 

  • Parkinson FE, Friesen J, Krizanac-Bengez L, Janigro D. 2003. Use of three-dimensional in vitro model of the rat blood-brain barrier to assay nucleoside efflux from brain. Brain Res 980: 233–241.

    Article  CAS  PubMed  Google Scholar 

  • Parkinson FE, Hacking C. 2005. Pericyte abundance affects sucrose permeability in cultures of rat brain microvascular endothelial cells. Brain Res 1049: 8–14.

    Article  CAS  PubMed  Google Scholar 

  • Perrière N, Demeuse P, Garcia E, Regina A, Debray M, et al. 2005. Puromycin-based purification of rat brain capillary endothelial cell cultures. Effect on the expression of blood-brain barrier-specific properties. J Neurochem 93: 279–289.

    Article  PubMed  CAS  Google Scholar 

  • Plateel M, Dehouck M-P, Torpier G, Cecchelli R, Teissier E. 1995. Hypoxia increases the susceptibility to oxidant stress and the permeability of the blood-brain barrier endothelial cell monolayer. J Neurochem 65: 2138–2145.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Preston JE, Hipkiss AR, Himsworth DT, Romero IA, Abbott JN. 1998. Toxic effects of beta-amyloid(25–35) on immortalised rat brain endothelial cell: Protection by carnosine, homocarnosine and beta-alanine. Neurosci Lett 242: 105–108.

    Article  CAS  PubMed  Google Scholar 

  • Raub TJ. 1996. Signal transduction and glial cell modulation of cultured brain microvessel endothelial cell tight junctions. Am J Physiol Cell Physiol 271: C495–C503.

    CAS  Google Scholar 

  • Raub TJ, Kuentzel SL, Sawada GA. 1992. Permeability of bovine brain microvessel endothelial cells in vitro: Barrier tightening by a factor released from astroglioma cells. Exp Cell Res 199: 330–340.

    Article  CAS  PubMed  Google Scholar 

  • Ramsohoye PV, Fritz IB. 1998. Preliminary characterization of glial-secreted factors responsible for the induction of high electrical resistances across endothelial monolayers in a blood-brain barrier model. Neurochem Res 23: 1545–1551.

    Article  CAS  PubMed  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  CAS  PubMed  Google Scholar 

  • Reichel A, Begley DJ, Abbott NJ. 2003. An overview of in vitro techniques for blood-brain barrier studies. The Blood-Brain Barrier: Biology and Research Protocols. Nag S, editor. Methods in Molecular Medicine, Vol. 89. Totowa, NJ: Humana Press.

    Chapter  Google Scholar 

  • Romero IA, Prevost M-C, Perret E, Adamson P, Greenwood J, et al. 2000. Interactions between brain endothelial cells and human T-cell leukemia virus type 1-infected lymphocytes: Mechanisms of viral entry into the central nervous system. J Virol 74: 6021–6030.

    Article  CAS  PubMed  Google Scholar 

  • Romero IA, Radewicz K, Jubin E, Michel CC, Greenwood J, et al. 2003. Changes in cytoskeletal and tight junctional proteins correlate with decreased permeability induced by dexamethasone in cultured rat brain endothelial cells. Neurosci Lett 344: 112–116.

    Article  CAS  PubMed  Google Scholar 

  • Roux F, Couraud P-O. 2005. Rat brain endothelial cell lines for the study of blood-brain barrier permeability and transport functions. Cell Mol Neurobiol 25: 41–58.

    Article  PubMed  Google Scholar 

  • Rubin LL, Hall DE, Porter S, Barbu K, Cannon C, et al. 1991. A cell culture model of the blood-brain barrier. J Cell Biol 115: 1725–1735.

    Article  CAS  PubMed  Google Scholar 

  • Rubin LL, Staddon JM. 1999. The cell biology of the blood-brain barrier. Annu Rev Neurosci 22: 11–28.

    Article  CAS  PubMed  Google Scholar 

  • Rutten MJ, Hoover RL, Karnovsky MJ. 1987. Electrical resistance and macromolecular permeability of brain endothelial monolayer cultures. Brain Res 425: 301–310.

    Article  CAS  PubMed  Google Scholar 

  • Sahagun G, Moore SA, Hart MN. 1990. Permeability of neutral vs. anionic dextrans in cultured brain microvascular endothelium. Am J Physiol 259: H162–H166.

    CAS  PubMed  Google Scholar 

  • Sakaeda T, Siahaan TJ, Audus KL, Stella VJ. 2000. Enhancement of transport of d-melphalan analogue by conjugation with l-glutamate across bovine brain microvessel endothelial cell monolayers. J Drug Target 8: 195–204.

    Article  CAS  PubMed  Google Scholar 

  • Schiera G, Bono E, Raffa MP, Gallo A, Pitarresi GL, et al. 2003. Synergistic effects of neurons and astrocytes on the differentiation of brain capillary endothelial cells in culture. J Cell Mol Med 7: 165–170.

    Article  PubMed  Google Scholar 

  • Schiera G, Sala S, Gallo A, Raffa MP, Pitarresi GL, et al. 2005. Permeability properties of a three-cell type in vitro model of blood-brain barrier. J Cell Mol Med 9: 373–379.

    Article  CAS  PubMed  Google Scholar 

  • Shen Q, Goderie SK, Jin L, Karanth N, Sun Y, et al. 2004. Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells. Science 304: 1338–1340.

    Article  CAS  PubMed  Google Scholar 

  • Smith KR, Borchardt RT. 1989. Permeability and mechanism of albumin, cationized albumin, and glycosylated albumin transcellular transport across monolayers of cultured bovine brain capillary endothelial cells. Pharm Res 6: 466–473.

    Article  CAS  PubMed  Google Scholar 

  • Sobue K, Yamamoto N, Yoneda K, Hodgson ME, Yamashiro K, et al. 1999. Induction of blood-brain barrier properties in immortalized bovine brain endothelial cells by astrocytic factors. Neurosci Res 35: 155–164.

    Article  CAS  PubMed  Google Scholar 

  • Song HS, Son MJ, Lee YM, Kim WJ, Lee S-W, et al. 2002. Oxygen tension regulates the maturation of the blood-brain barrier. Biochem Biophys Res Commun 290: 325–331.

    Article  CAS  PubMed  Google Scholar 

  • Stanness KA, Neumaier JF, Sexton TJ, Grant GA, Emmi A, et al. 1999. A new model of the blood-brain barrier: Co-culture of neuronal, endothelial, and glial cells under dynamic conditions. Neuroreport 10: 3725–3731.

    Article  CAS  PubMed  Google Scholar 

  • Stins MF, Badger J, Kim KS. 2001. Bacterial invasion and transcytosis in transfected human brain microvascular endothelial cells. Microb Pathog 30: 19–28.

    Article  CAS  PubMed  Google Scholar 

  • Strazielle N, Ghersi-Egea JF, GhisoJ, Dehouck M-P, Frangione B, et al. 2000. In vitro evidence that beta-amyloid peptide 1-40 diffuses across the blood-brain barrier and affects its permeability. J Neuropathol Exp Neurol 59: 29–38.

    CAS  PubMed  Google Scholar 

  • Suda K, Rothen-Rutishauser B, Gunthert M, Wunderli- Allenspach H. 2001. Phenotypic characterization of human umbilical vein endothelial (ECV304) and urinary carcinoma (T24) cells: Endothelial versus epithelial features. In Vitro Cell Dev Biol Anim 37: 505–514.

    Article  CAS  PubMed  Google Scholar 

  • Tan KH, Dobbie MS, Felix RA, Barrand MA, Hurst RD. 2001. A comparison of the induction of immortalized endothelial cell impermeability by astrocytes. Neuroreport 12: 1329–1334.

    Article  CAS  PubMed  Google Scholar 

  • Tao-Cheng JH, Nagy Z, Brightman MW. 1987. Tight junctions of brain endothelium in vitro are enhanced by astroglia. J Neurosci 7: 3293–3299.

    CAS  PubMed  Google Scholar 

  • Terasaki T, Ohtsuki S, Hori S, Takanaga H, Nakashima E, et al. 2003. New approaches to in vitro models of blood-brain barrier drug transport. Drug Discov Today 8: 944–954.

    Article  CAS  PubMed  Google Scholar 

  • Tilling T, Korte D, Hoheisel D, Galla H-J. 1998. Basement membrane proteins influence brain capillary endothelial barrier function in vitro. J Neurochem 71: 1151–1157.

    Article  CAS  PubMed  Google Scholar 

  • Tilloy S, Monnaert V, Fenart L, Bricout H, Cecchelli R, et al. 2006. Methylated beta-cyclodextrin as P-gp modulators for deliverance of doxorubicin across an in vitro model of blood-brain barrier. Bioorg Med Chem Lett 16: 2154–2157.

    Article  CAS  PubMed  Google Scholar 

  • Trottein F, Descamps L, Nutten S, Dehouck M-P, Angeli V, et al. 1999. Schistosoma mansoni activates host microvascular endothelial cells to acquire an anti-inflammatory phenotype. Infect Immun 67: 3403–3409.

    CAS  PubMed  Google Scholar 

  • Tsuji A, Tamai I. 1999. Carrier-mediated or specialized transport of drugs across the blood-brain barrier. Adv Drug Deliv Rev 36: 277–290.

    Article  CAS  PubMed  Google Scholar 

  • Tunkel AR, Rosser SW, Hansen EJ, Scheld WM. 1991. Blood-brain barrier alterations in bacterial meningitis: Development of an in vitro model and observations on the effects of lipopolysaccharide. In Vitro Cell Dev Biol 27A:113–120.

    Article  CAS  PubMed  Google Scholar 

  • Ueda Y, Nakagawa T, Kubota T, Ido K, Sato K. 2005. Glioma cells under hypoxic conditions block the brain microvascular endothelial cell death induced by serum starvation. J Neurochem 95: 99–110.

    Article  CAS  PubMed  Google Scholar 

  • Utepbergenov DI, Mertsch K, Sporbert A, Tenz K, Paul M, et al. 1998. Nitric oxide protects blood-brain barrier in vitro from hypoxia/reoxygenation-mediated injury. FEBS Lett 424: 197–201.

    Article  CAS  PubMed  Google Scholar 

  • Valable S, Montaner J, Bellail A, Berezowski V, Brillault J, et al. 2005. VEGF-induced BBB permeability is associated with an MMP-9 activity increase in cerebral ischemia: Both effects decreased by Ang-1. J Cereb Blood Flow Metab 25: 1491–1504.

    Article  CAS  PubMed  Google Scholar 

  • van der Sandt IC, Gaillard PJ, Voorwinden HH, de Boer AG, Breimer DD. 2001. P-glycoprotein inhibition leads to enhanced disruptive effects by anti-microtubule cytostatics at the in vitro blood-brain barrier. Pharm Res 18: 587–592.

    Article  CAS  PubMed  Google Scholar 

  • Walshe TE, Ferguson G, Connell P, O'Brien C, Cahill PA. 2005. Pulsatile flow increases the expression of eNOS, ET-1, and prostacyclin in a novel in vitro coculture model of the retinal vasculature. Invest Ophthalmol Vis Sci 46: 375–382.

    Article  PubMed  Google Scholar 

  • Wang W, Merrill MJ, Borchardt RT. 1996. Vascular endothelial growth factor affects permeability of brain microvessel endothelial cells in vitro. Am J Physiol Cell Physiol 271: C1973–C1980.

    CAS  Google Scholar 

  • Weidenfeller C, Schrot S, Zozulya A, Galla H-J. 2005. Murine brain capillary endothelial cells exhibit improved barrier properties under the influence of hydrocortisone. Brain Res 1053: 162–174.

    Article  CAS  PubMed  Google Scholar 

  • Weksler BB, Subileau EA, Perrière N, Charneau P, Holloway K, et al. 2005. Blood-brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J 19: 1872–1874.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Yamagata K, Tagami M, Nara Y, Fujino H, Kubota A, et al. 1997. Faulty induction of blood-brain barrier functions by astrocytes isolated from stroke-prone spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 24: 686–691.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Youdim KA, Avdeef A, Abbott NJ. 2003. In vitro trans-monolayer permeability calculations: Often forgotten assumptions. Drug Discov Today 8: 997–1003.

    Article  CAS  PubMed  Google Scholar 

  • Zenker D, Begley D, Bratzke H, Rübsamen-Waigmann H, von Briesen H. 2003. Human blood-derived macrophages enhance barrier function of cultured brain capillary endothelial cells. J Physiol 551: 1023–1032.

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Harder DR. 2002. Cerebral capillary endothelial cell mitogenesis and morphogenesis induced by astrocytic epoxyeicosatrienoic acid. Stroke 33: 2957–2964.

    Article  CAS  PubMed  Google Scholar 

  • Zysk G, Schneider-Wald BK, Hwang JH, Bejo L, Kim KS, et al. 2001. Pneumolysin in the main inducer of cytotoxicity to brain microvascular endothelial cells caused by Streptococcus pneumoniae. Infect Immun 69: 845–852.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the Hungarian Research Fund (OTKA T37834) and National Office for Research and Technology (RET 08/2004). The help of Dr. Csongor Ábrahám in critical reading of this chapter is gratefully acknowledged.

Authors
  1. M. A. Deli
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, New York, 10962, Orangeburg, USA

    Abel Lajtha

  2. Department of Psychiatry Millhauser Labs, Room MHL‐HN–604A, New York University School of Medicine, 550 First Avenue, N.Y. 10016, New York, USA

    Maarten E. A. Reith Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer Science+Business Media, LLC.

About this entry

Cite this entry

Deli, M.A. (2007). Blood–Brain Barrier Models. In: Lajtha, A., Reith, M.E.A. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30380-2_2

Download citation

Publish with us

Policies and ethics

Search

Navigation