Summary.
In this paper we discuss the importance of the blood–brain barrier (BBB) as an interface between blood and brain. Many (brain) diseases change the functionality and integrity of the BBB. Mostly this results in increased BBB permeability. Therefore we have studied de various signal transduction routes that are influenced by inflammatory stimuli. The radical scavenger N-acetylcysteine was able to protect the BBB against inflammatory stimuli. Similar results were found following application of glucocorticoids. In addition, it was observed that glucocorticoids and interferon-α,β increased the tightness of the in vitro BBB and when given together a potentiating effect was seen.
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References
KL Audus RT Borchardt (1986) ArticleTitleCharacterization of an in vitro blood–brain barrier model system for studying drug transport and metabolism. Pharm Res 3 81–87 Occurrence Handle10.1023/A:1016337202335 Occurrence Handle1:CAS:528:DyaL28XktlGjtrk%3D
HG Augustin DH Kozian RC Johnson (1994) ArticleTitleDifferentiation of endothelial cells: analysis of the constitutive and activated endothelial cell phenotypes. Bioessays 16 IssueID12 901–906 Occurrence Handle10.1002/bies.950161208 Occurrence Handle1:CAS:528:DyaK2MXjs1yrt7s%3D Occurrence Handle7840769
KL Black (1995) ArticleTitleBiochemical opening of the blood–brain barrier. Adv Drug Deliv Rev 15 37–52 Occurrence Handle10.1016/0169-409X(95)00004-Q Occurrence Handle1:CAS:528:DyaK2MXntFClsr8%3D
AM Blamire DC Anthony B Rajagopalan NR Sibson VH Perry P Styles (2000) ArticleTitleInterleukin-1beta-induced changes in blood–brain barrier permeability, apparent diffusion coefficient, and cerebral blood volume in the rat brain: a magnetic resonance study. J Neurosci 20 IssueID21 8153–8159 Occurrence Handle1:CAS:528:DC%2BD3cXnsl2mtLs%3D Occurrence Handle11050138
KM Boje (1995) ArticleTitleCerebrovascular permeability changes during experimental meningitis in the rat. J Pharmacol Exp Ther 274 1199–1203 Occurrence Handle1:CAS:528:DyaK2MXot1yjsL8%3D Occurrence Handle7562488
AM Butt (1995) ArticleTitleEffect of inflammatory agents on electrical resistance across the blood–brain barrier in pial microvessels of anaesthetized rats. Brain Res 696 145–150 Occurrence Handle10.1016/0006-8993(95)00811-4 Occurrence Handle1:CAS:528:DyaK2MXovVyhuro%3D Occurrence Handle8574662
de Boer AG, Sutanto W (eds) (1997) Drug transport across the blood–brain barrier: new experimental strategies. Harwood Scientific Publisher, Amsterdam
AG de Boer PJ Gaillard (2002) ArticleTitleIn vitro models of the blood–brain barrier: when to use which? Current Medicinal Chemistry – Central Nervous System Agents 2 IssueID3 203–209 Occurrence Handle1:CAS:528:DC%2BD38XmtVOhs7Y%3D
AG de Boer ICJ van der Sandt PJ Gaillard (2003) ArticleTitleThe role of drug transporters at the BBB. Ann Rev Pharmacol Tox 43 629–656 Occurrence Handle1:CAS:528:DC%2BD3sXitFWqt70%3D
HE de Vries EF Eppens M Prins J Kuiper ThJC Van Berkel AG De Boer DD Breimer (1995) ArticleTitleBlood–brain barrier permeability during experimental allergic encephalomyelitis and acute septic shock. Pharm Res 12 IssueID12 1932–1936 Occurrence Handle10.1023/A:1016291806357 Occurrence Handle1:CAS:528:DyaK28Xis12jtA%3D%3D Occurrence Handle8786968
M-P Dehouck S Méresse P Delorme J-C Fruchart R Cecchelli (1990) ArticleTitleAn easier, reproducible, and mass-production method to study the blood–brain barrier in vitro. J Neurochem 54 1798–1801 Occurrence Handle1:CAS:528:DyaK3cXitlaitLk%3D Occurrence Handle2182777
PJ Gaillard AG De Boer (2000) ArticleTitleRelationship between permeability status of the blood–brain barrier and in vitro permeability coefficient of a drug. Eur J Pharm Sci 12 95–102 Occurrence Handle1:CAS:528:DC%2BD3cXotlGjsLs%3D Occurrence Handle11102736
PJ Gaillard AG De Boer DD Breimer (2003) ArticleTitlePharmacological investigations on lipopolysaccharide-induced permeability changes in the blood–brain barrier in vitro. Microvasc Res 65 IssueID1 24–31 Occurrence Handle10.1016/S0026-2862(02)00009-2 Occurrence Handle1:CAS:528:DC%2BD3sXlt12qsQ%3D%3D Occurrence Handle12535868
PJ Gaillard LH Voorwinden JL Nielsen A Ivanov R Atsumi H Engman C Ringbom AG De Boer DD Breimer (2001) ArticleTitleEstablishment and functional characterization of an in vitro model of the blood–brain barrier, comprising a co-culture of brain capillary endothelial cells and astrocytes. Eur J Pharm Sci 12 215–222 Occurrence Handle1:CAS:528:DC%2BD3cXoslGhtLs%3D Occurrence Handle11113640
PJ Gaillard PH Van Der Meide AG De Boer DD Breimer (2001) ArticleTitleGlucocorticoid and type I interferon interactions at the blood–brain barrier: relevance for drug therapies for multiple sclerosis. Neuroreport 12 IssueID10 2189–2193 Occurrence Handle1:CAS:528:DC%2BD3MXls1emsrw%3D Occurrence Handle11447332
MC Gillies T Su (1995) ArticleTitleInterferon-alpha 2b enhances barrier function of bovine retinal microvascular endothelium in vitro. Microvasc Res 49 IssueID3 277–288 Occurrence Handle10.1006/mvre.1995.1024 Occurrence Handle1:CAS:528:DyaK2MXms12lsLo%3D Occurrence Handle7643749
M Gumbleton KL Audus (2001) ArticleTitleProgress 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 IssueID11 1681–1698 Occurrence Handle10.1002/jps.1119 Occurrence Handle1:CAS:528:DC%2BD3MXosVKltrw%3D Occurrence Handle11745727
M Harzheim M Stepien-Mering R Schroder S Schmidt (2004) ArticleTitleThe expression of microfilament-associated cell–cell contacts in brain endothelial cells is modified by IFN-beta1a (Rebif). J Interferon Cytokine Res 24 IssueID12 711–716 Occurrence Handle1:CAS:528:DC%2BD2cXhtFSjtr7M Occurrence Handle15684738
D Hoheisel T Nitz H Franke J Wegener A Hakvoort T Tilling HJ Galla (1998) ArticleTitleHydrocortisone reinforces the blood–brain properties in a serum free cell culture system. Biochem Biophys Res Commun 247 IssueID2 312–315 Occurrence Handle1:STN:280:DyaK1czjsFGnuw%3D%3D Occurrence Handle9679029
InstitutionalAuthorNameIFNB Multiple Sclerosis Study Group (1993) ArticleTitleInterferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology 43 655–661
InstitutionalAuthorNameIFNB Multiple Sclerosis Study Group and University of British Columbia MS/MRI Analysis Group (1995) ArticleTitleInterferon beta-1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology 45 1277–1285
RC Janzer MC Raff (1987) ArticleTitleAstrocytes induce blood–brain barrier properties in endothelial cells. Nature 325 253–257 Occurrence Handle10.1038/325253a0 Occurrence Handle1:STN:280:BiiC3MrnslQ%3D Occurrence Handle3543687
J Kraus AK Ling S Hamm K Voigt P Oschmann B Engelhardt (2005) ArticleTitleInterferon-beta stabilizes barrier characteristics of brain endothelial cells in vitro. Ann Neurol 56 IssueID2 192–205
Y Kustova A Grinberg AS Basile (1999) ArticleTitleIncreased blood–brain barrier permeability in lp-bm5 infected mice is mediated by neuroexcitatory mechanisms. Brain Res 839 IssueID1 153–163 Occurrence Handle10.1016/S0006-8993(99)01734-5 Occurrence Handle1:CAS:528:DyaK1MXlt1Shsb8%3D Occurrence Handle10482808
P Lagrange IA Romero A Minn PA Revest (1999) ArticleTitleTransendothelial permeability changes induced by free radicals in an in vitro model of the blood–brain barrier. Free Radic Biol Med 27 IssueID5–6 667–672 Occurrence Handle1:CAS:528:DyaK1MXls12ns7Y%3D Occurrence Handle10490287
KM Mattila T Pirtilä K Blennow A Wallin M Vitanen H Frey (1994) ArticleTitleAltered blood–brain barrier function in alzheimer’s disease? Acta Neurol Scand 89 192–198 Occurrence Handle1:CAS:528:DyaK2cXkvVSit7s%3D Occurrence Handle8030400
JE Merrill SP Murphy (1997) ArticleTitleInflammatory events at the blood brain barrier: regulation of adhesion molecules, cytokines, and chemokines by reactive nitrogen and oxygen species. Brain Behav Immun 11 IssueID4 245–263 Occurrence Handle10.1006/brbi.1997.0496 Occurrence Handle1:CAS:528:DyaK1cXit1aqtr4%3D Occurrence Handle9512813
N Müller (1995) ArticleTitlePsychoneuroimmunology: implications for the drug treatment of psychiatric disorders. CNS Drugs 4 IssueID2 125–140
Pardridge WM (1991) Peptide drug delivery to the brain. Raven Press, New York
SD Poland GPA Rice GA Dekaban (1995) ArticleTitleHIV-1 infection of human brain-derived microvascular endothelial cells in vitro. J Acquir Immune Defic Syndr Hum Retrovirol 8 437–445 Occurrence Handle1:STN:280:ByqB3M7ltlE%3D Occurrence Handle7697439
M Ramsauer J Kunz D Krause R Dermietzel (1998) ArticleTitleRegulation of a blood–brain barrier- specific enzyme expressed by cerebral pericytes (pericytic aminopeptidase) under cell culture conditions. J Cereb Blood Flow Metab 18 1270–1281 Occurrence Handle1:CAS:528:DyaK1cXnsFSqsrw%3D Occurrence Handle9809517
M Schluep J Bogousslavsky (1997) ArticleTitleEmerging treatments in multiple sclerosis. Eur Neurol 38 216–221 Occurrence Handle1:STN:280:DyaK1c%2FivVCltg%3D%3D Occurrence Handle9363834
N Tsao HP Hsu CM Wu CC Liu HY Lei (2001) ArticleTitleTumor necrosis factor-alpha causes an increase in blood–brain barrier permeability during sepsis. J Med Microbiol 50 IssueID9 812–821 Occurrence Handle1:CAS:528:DC%2BD3MXntVKhtLs%3D Occurrence Handle11549183
A Tunkel WM Scheld (1993) ArticleTitlePathogenesis and pathophysiology of bacterial meningitis. Ann Rev Med 44 103–120 Occurrence Handle10.1146/annurev.me.44.020193.000535 Occurrence Handle1:CAS:528:DyaK3sXkt1Gms70%3D Occurrence Handle8476234
KC Williams WF Hickey (1994) ArticleTitleImmunology of multiple sclerosis. Clin Neurosci 2 229–245 Occurrence Handle1:STN:280:ByqB28bgtlU%3D Occurrence Handle7749893
J Wilting B Brand-Saberi H Kurz B Christ (1995) ArticleTitleDevelopment of the embryonic vascular system. Cell Mol Biol Res 41 IssueID4 219–232 Occurrence Handle1:CAS:528:DyaK28XotlKmsQ%3D%3D Occurrence Handle8775980
J Wilting B Christ (1989) ArticleTitleAn experimental and ultrastructural study on the development of the avian choroid plexus. Cell Tissue Res 255 487–494 Occurrence Handle10.1007/BF00218783 Occurrence Handle1:STN:280:BiaB3cfntl0%3D Occurrence Handle2706656
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de Boer, A., Gaillard, P. Blood–brain barrier dysfunction and recovery. J Neural Transm 113, 455–462 (2006). https://doi.org/10.1007/s00702-005-0375-4
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DOI: https://doi.org/10.1007/s00702-005-0375-4