nach oben

Seminars in Immunopathology

Erschienen in:

01.11.2009 | Review

The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction

verfasst von: Britta Engelhardt, Lydia Sorokin

Erschienen in: Seminars in Immunopathology | Ausgabe 4/2009

Einloggen, um Zugang zu erhalten

Abstract

The central nervous system (CNS) is tightly sealed from the changeable milieu of blood by the blood–brain barrier (BBB) and the blood–cerebrospinal fluid (CSF) barrier (BCSFB). While the BBB is considered to be localized at the level of the endothelial cells within CNS microvessels, the BCSFB is established by choroid plexus epithelial cells. The BBB inhibits the free paracellular diffusion of water-soluble molecules by an elaborate network of complex tight junctions (TJs) that interconnects the endothelial cells. Combined with the absence of fenestrae and an extremely low pinocytotic activity, which inhibit transcellular passage of molecules across the barrier, these morphological peculiarities establish the physical permeability barrier of the BBB. In addition, a functional BBB is manifested by a number of permanently active transport mechanisms, specifically expressed by brain capillary endothelial cells that ensure the transport of nutrients into the CNS and exclusion of blood-borne molecules that could be detrimental to the milieu required for neural transmission. Finally, while the endothelial cells constitute the physical and metabolic barrier per se, interactions with adjacent cellular and acellular layers are prerequisites for barrier function. The fully differentiated BBB consists of a complex system comprising the highly specialized endothelial cells and their underlying basement membrane in which a large number of pericytes are embedded, perivascular antigen-presenting cells, and an ensheathment of astrocytic endfeet and associated parenchymal basement membrane. Endothelial cell morphology, biochemistry, and function thus make these brain microvascular endothelial cells unique and distinguishable from all other endothelial cells in the body. Similar to the endothelial barrier, the morphological correlate of the BCSFB is found at the level of unique apical tight junctions between the choroid plexus epithelial cells inhibiting paracellular diffusion of water-soluble molecules across this barrier. Besides its barrier function, choroid plexus epithelial cells have a secretory function and produce the CSF. The barrier and secretory function of the choroid plexus epithelial cells are maintained by the expression of numerous transport systems allowing the directed transport of ions and nutrients into the CSF and the removal of toxic agents out of the CSF. In the event of CNS pathology, barrier characteristics of the blood–CNS barriers are altered, leading to edema formation and recruitment of inflammatory cells into the CNS. In this review we will describe current knowledge on the cellular and molecular basis of the functional and dysfunctional blood–CNS barriers with focus on CNS autoimmune inflammation.

Ehrlich P (1904) Über die Beziehung chemischer Constitution, Vertheilung, und pharmakologischer Wirkung. Berlin

Goldmann EE (1913) Vitalfärbung am Zentralnervensystem. Abh Preuss Wissensch Phys-Math 1:1–60

Lewandowsky M (1890) Zur Lehre der Zerebrospinalflüssigkeit. Z Klin Med 40:480–494

Biedl A, Kraus R (1898) Über eine bisher unbekannte toxische Wirkung der Gallensäure auf das Zentralnervensystem. Zentralbl Inn Med 19:1185–1200

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

Leonhardt H (1980) Ependym und circumventriculäre Organe. In: Oksche A, Vollrath L (eds) Handbuch der mikroskopischen Anatomie des Menschen. Springer, Berlin, pp 177–666

Engelhardt B, Wolburg-Buchholz K, Wolburg H (2001) Involvement of the choroid plexus in central nervous system inflammation. Microsc Res Tech 52(1):112–129PubMedCrossRef

Bouchaud C, Bosler O (1986) The circumventricular organs of the mammalian brain with special reference to monoaminergic innervation. IntRevCytol 105:283–327

Alcolado R, Weller RO, Parrish EP, Garrod D (1988) The cranial arachnoid and piamater in man: anatomical and ultrastructural observations. Neuropathol Appl Neurobiol 14:1–17PubMedCrossRef

10.

Wolburg H (1995) Orthogonal arrays of intramembranous particles: a review with special reference to astrocytes. J Hirnforsch 36(2):239–258PubMed

11.

Zhang ET, Inman CBE, Weller RO (1990) Interrelationships of the pia mater and the perivascular (Virchow-Robin) spaces in the human cerebrum. J Anat 170:111–123PubMed

12.

Sixt M, Engelhardt B, Pausch F et al (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(5):933–946PubMedCrossRef

13.

Hawkins BT, Davis TP (2005) The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev 57(2):173–185PubMedCrossRef

14.

Wolburg H, Lippoldt A (2002) Tight junctions of the blood-brain barrier. Development, composition and regulation. Vasc Pharmacol 28:323–337CrossRef

15.

Furuse M, Hirase T, Itoh M et al (1993) Occludin: a novel integral membrane protein localizing at tight junctions. J Cell Biol 123(6 Pt 2):1777–1788PubMedCrossRef

16.

Saitou M, Furuse M, Sasaki H et al (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 22:4131–4142

17.

Furuse M, Tsukita S (2006) Claudins in occluding junctions of humans and flies. Trends Cell Biol 16(4):181–188PubMedCrossRef

18.

Wolburg H, Wolburg-Buchholz K, Kraus J et al (2003) Localization of claudin-3 in tight junctions of the blood-brain barrier is selectively lost during experimental autoimmune encephalomyelitis and human glioblastoma multiforme. Acta Neuropathol (Berl) 105(6):586–592

19.

Martin-Padura I, Lostaglio S, Schneemann M et al (1998) Junctional adhesion molecule, a novel member of the immunoglobulin superfamily that distributes at intercellular junctions and modulates monocyte transmigration. J Cell Biol 142(1):117–127PubMedCrossRef

20.

Nasdala I, Wolburg-Buchholz K, Wolburg H et al (2002) A transmembrane tight junction protein selectively expressed on endothelial cells and platelets. J Biol Chem 277(18):16294–16303PubMedCrossRef

21.

Tsukita S, Furuse M, Itoh M (1999) Structural and signalling molecules come together at tight junctions. Curr Opin Cell Biol 11(5):628–633PubMedCrossRef

22.

Dejana E, Orsenigo F, Lampugnani MG (2008) The role of adherens junctions and VE-cadherin in the control of vascular permeability. J Cell Sci 121(Pt 13):2115–2122PubMedCrossRef

23.

Dejana E, Tournier-Lasserve E, Weinstein BM (2009) The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications. Dev Cell 16(2):209–221PubMedCrossRef

24.

Breier G, Breviaro F, Caveda L et al (1996) Molecular cloning and expression of murine VE-cadherin in early developing cardiovascular system. Blood 87(2):630–641PubMed

25.

Taddei A, Giampietro C, Conti A et al (2008) Endothelial adherens junctions control tight junctions by VE-cadherin-mediated upregulation of claudin-5. Nature cell biology 10(8):923–934PubMedCrossRef

26.

Liebner S, Corada M, Bangsow T et al (2008) Wnt/beta-catenin signaling controls development of the blood-brain barrier. J Cell Biol 183(3):409–417PubMedCrossRef

27.

Hallmann R, Mayer DN, Berg EL, Broermann R, Butcher EC (1995) Novel mouse endothelial cell surface marker is suppressed during differentiation of the blood brain barrier. Dev Dyn 202(4):325–332PubMed

28.

Graesser D, Solowiej A, Bruckner M et al (2002) Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice. J Clin Invest 109(3):383–392PubMed

29.

Davson H, Oldendorf WH (1967) Symposium on membrane transport. Transport in the central nervous system. Proc R Soc Med 60(4):326–329PubMed

30.

Janzer RC, Raff MC (1987) Astrocytes induce blood-brain barrier properties in endothelial cells. Nature 325(6101):253–257PubMedCrossRef

31.

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

32.

Abbott NJ, Ronnback L, Hansson E (2006) Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 7(1):41–53PubMedCrossRef

33.

Nicholas DS, Weller RO (1988) The fine anatomy of the human spinal meninges. A light and scanning electron microscopy study. J Neurosurg 69(2):276–282PubMedCrossRef

34.

Hutchings M, Weller RO (1986) Anatomical relationships of the pia mater to cerebral blood vessels in man. J Neurosurg 65(3):316–325PubMedCrossRef

35.

Garberg P, Ball M, Borg N et al (2005) In vitro models for the blood-brain barrier. Toxicol In Vitro 19(3):299–334PubMedCrossRef

36.

Gerhardt H, Betsholtz C (2003) Endothelial-pericyte interactions in angiogenesis. Cell Tissue Res 314(1):15–23PubMedCrossRef

37.

Bondjers C, He L, Takemoto M et al (2006) Microarray analysis of blood microvessels from PDGF-B and PDGF-Rbeta mutant mice identifies novel markers for brain pericytes. Faseb J 20(10):1703–1705PubMedCrossRef

38.

Lindahl P, Johansson BR, Leveen P, Betsholtz C (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277:242–245PubMedCrossRef

39.

Lindblom P, Gerhardt H, Liebner S et al (2003) Endothelial PDGF-B retention is required for proper investment of pericytes in the microvessel wall. Genes Dev 17(15):1835–1840PubMedCrossRef

40.

Timpl R (1989) Structure and biological activity of basement membrane proteins. Eur J Biochem 180:487–502PubMedCrossRef

41.

Hallmann R, Horn N, Selg M et al (2005) Expression and function of laminins in the embryonic and mature vasculature. Physiol Rev 85(3):979–1000PubMedCrossRef

42.

del Zoppo GJ, Milner R (2006) Integrin-matrix interactions in the cerebral microvasculature. Arterioscler Thromb Vasc Biol 26(9):1966–1975PubMedCrossRef

43.

Del Zoppo GJ, Milner R, Mabuchi T et al (2006) Vascular matrix adhesion and the blood-brain barrier. Biochem Soc Trans 34(Pt 6):1261–1266PubMed

44.

Agrawal S, Anderson P, Durbeej M et al (2006) Dystroglycan is selectively cleaved at the parenchymal basement membrane at sites of leukocyte extravasation in experimental autoimmune encephalomyelitis. J Exp Med 203(4):1007–1019PubMedCrossRef

45.

Wu C, Ivars F, Anderson P et al (2009) Endothelial basement membrane laminin alpha5 selectively inhibits T lymphocyte extravasation into the brain. Nat Med 15(5):519–527PubMedCrossRef

46.

Jucker M, Tian M, Norton DD, Sherman C, Kusiak JW (1996) Laminin alpha 2 is a component of brain capillary basement membrane: reduced expression in dystrophic dy mice. Neuroscience 71:1153–1161PubMedCrossRef

47.

Zhou FC (1990) Four patterns of laminin-immunoreactive structure in developing rat brain. Brain Res Dev Brain Res 55(2):191–201PubMedCrossRef

48.

Vahedi K, Kubis N, Boukobza M et al (2007) COL4A1 mutation in a patient with sporadic, recurrent intracerebral hemorrhage. Stroke 38(5):1461–1464PubMedCrossRef

49.

Gould DB, Phalan FC, Breedveld GJ et al (2005) Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science 308(5725):1167–1171PubMedCrossRef

50.

Poschl E, Schlotzer-Schrehardt U, Brachvogel B et al (2004) Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development 131(7):1619–1628PubMedCrossRef

51.

Wolburg-Buchholz K, Mack AF, Steiner E et al (2009) Loss of astrocyte polarity marks blood-brain barrier impairment during experimental autoimmune encephalomyelitis. Acta Neuropathol 118(2):219–233PubMedCrossRef

52.

Brachvogel B, Pausch F, Farlie P et al (2007) Isolated Anxa5+/Sca-1+ perivascular cells from mouse meningeal vasculature retain their perivascular phenotype in vitro and in vivo. Exp Cell Res 313(12):2730–2743PubMedCrossRef

53.

Betsholtz C, Lindblom P, Bjarnegard M et al (2004) Role of platelet-derived growth factor in mesangium development and vasculopathies: lessons from platelet-derived growth factor and platelet-derived growth factor receptor mutations in mice. Curr Opin Nephrol Hypertens 13(1):45–52PubMedCrossRef

54.

Durbeej M, Henry MD, Ferletta M, Campbell KP, Ekblom P (1998) Distribution of dystroglycan in normal adult mouse tissues. J Histochem Cytochem 46:449–458PubMed

55.

Milner R (2009) Microglial expression of alphavbeta3 and alphavbeta5 integrins is regulated by cytokines and the extracellular matrix: beta5 integrin null microglia show no defects in adhesion or MMP-9 expression on vitronectin. Glia 57(7):714–723PubMedCrossRef

56.

Proctor JM, Zang K, Wang D, Wang R, Reichardt LF (2005) Vascular development of the brain requires beta8 integrin expression in the neuroepithelium. J Neurosci 25(43):9940–9948PubMedCrossRef

57.

Zhu J, Motejlek K, Wang D et al (2002) beta8 integrins are required for vascular morphogenesis in mouse embryos. Development 129(12):2891–2903PubMed

58.

Bader BL, Rayburn H, Crowley D, Hynes RO (1998) Extensive vasculogenesis, angiogenesis and organogenesis precede lethality in mice lacking all av integrins. Cell 95:507–519PubMedCrossRef

59.

McCarty JH, Monahan-Earley RA, Brown LF et al (2002) Defective associations between blood vessels and brain parenchyma lead to cerebral hemorrhage in mice lacking alphav integrins. Mol Cell Biol 22:7667–7777PubMedCrossRef

60.

Moore SA, Saito F, Chen J et al (2002) Deletion of brain dystroglycan recapitulates aspects of congenital muscular dystrophy. Nature 418(6896):422–425PubMedCrossRef

61.

Ohtsuki S, Terasaki T (2007) Contribution of carrier-mediated transport systems to the blood-brain barrier as a supporting and protecting interface for the brain; importance for CNS drug discovery and development. Pharm Res 24(9):1745–1758PubMedCrossRef

62.

Boado RJ, Pardridge WM (1993) Glucose deprivation causes posttranscriptional enhancement of brain capillary endothelial glucose transporter gene expression via GLUT1 mRNA stabilization. J Neurochem 60(6):2290–2296PubMedCrossRef

63.

Lyck R, Ruderisch N, Moll AG, et al. (2009) Culture-induced changes in blood-brain barrier transcriptome: implications for amino-acid transporters in vivo. J Cereb Blood Flow Metab 29:1491–1502

64.

Lee HJ, Engelhardt B, Lesley J, Bickel U, Pardridge WM (2000) Targeting rat anti-mouse transferrin receptor monoclonal antibodies through blood-brain barrier in mouse. J Pharmacol Exp Ther 292(3):1048–1052PubMed

65.

Banks WA (2005) Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des 11(8):973–984PubMedCrossRef

66.

Begley DJ (2004) ABC transporters and the blood-brain barrier. Curr Pharm Des 10(12):1295–1312PubMedCrossRef

67.

Hickey WF, Hsu BL, Kimura H (1991) T-lymphocyte entry into the central nervous system. J Neurosci Res 28(2):254–260PubMedCrossRef

68.

Wekerle H, Linington C, Lassmann H, Meyermann R (1986) Cellular immune reactivity within the CNS. TINS 9:271–277

69.

Vajkoczy P, Laschinger M, Engelhardt B (2001) Alpha4-integrin-VCAM-1 binding mediates G protein-independent capture of encephalitogenic T cell blasts to CNS white matter microvessels. J Clin Invest 108(4):557–565PubMed

70.

Laschinger M, Vajkoczy P, Engelhardt B (2002) Encephalitogenic T cells use LFA-1 during transendothelial migration but not during capture and adhesion in spinal cord microvessels in vivo. Eur J Immunol 32:3598–3606PubMedCrossRef

71.

Kerfoot SM, Norman MU, Lapointe BM et al (2006) Reevaluation of P-selectin and alpha 4 integrin as targets for the treatment of experimental autoimmune encephalomyelitis. J Immunol 176:6225–6234PubMed

72.

Bauer M, Brakebusch C, Coisne C et al (2009) {beta}1 integrins differentially control extravasation of inflammatory cell subsets into the CNS during autoimmunity. Proc Natl Acad Sci U S A 106:1920–1925PubMedCrossRef

73.

Engelhardt B, Laschinger M, Schulz M et al (1998) The development of experimental autoimmune encephalomyelitis in the mouse requires alpha4-integrin but not alpha4beta7-integrin. J Clin Invest 102(12):2096–2105PubMedCrossRef

74.

Piccio L, Rossi B, Scarpini E et al (2002) Molecular mechanisms involved in lymphocyte recruitment in inflamed brain microvessels: critical roles for P-selectin glycoprotein ligand-1 and heterotrimeric G(i)-linked receptors. J Immunol 168:1940–1949PubMed

75.

Engelhardt B, Ransohoff RM (2005) The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol 26(9):485–495PubMedCrossRef

76.

Kerfoot S, Kubes P (2002) Overlapping roles of P-selectin and alpha 4 integrin to recruit leukocytes to the central nervous system in experimental autoimmune encephalomyelitis. J Immunol 169:1000–1006PubMed

77.

Osmers I, Bullard DC, Barnum SR (2005) PSGL-1 is not required for development of experimental autoimmune encephalomyelitis. J Neuroimmunol 166:193–196PubMedCrossRef

78.

Engelhardt B, Vestweber D, Hallmann R, Schulz M (1997) E- and P-selectin are not involved in the recruitment of inflammatory cells across the blood-brain barrier in experimental autoimmune encephalomyelitis. Blood 90(11):4459–4472PubMed

79.

Engelhardt B, Kempe B, Merfeld-Clauss S et al (2005) P-selectin glycoprotein ligand 1 is not required for the development of experimental autoimmune encephalomyelitis in SJL and C57BL/6 mice. J Immunol 175(2):1267–1275PubMed

80.

Doring A, Wild M, Vestweber D, Deutsch U, Engelhardt B (2007) E- and P-selectin are not required for the development of experimental autoimmune encephalomyelitis in C57BL/6 and SJL mice. J Immunol 179(12):8470–8479PubMed

81.

Uboldi C, Doring A, Alt C et al (2008) L-Selectin-deficient SJL and C57BL/6 mice are not resistant to experimental autoimmune encephalomyelitis. Eur J Immunol 38(8):2156–2167PubMedCrossRef

82.

Adamson P, Etienne S, Couraud PO, Calder V, Greenwood J (1999) Lymphocyte migration through brain endothelial cell monolayers involves signaling through endothelial ICAM-1 via a rho-dependent pathway. J Immunol 162(5):2964–2973PubMed

83.

Lyck R, Reiss Y, Gerwin N et al (2003) T cell interaction with ICAM-1/ICAM-2-double-deficient brain endothelium in vitro: the cytoplasmic tail of endothelial ICAM-1 is necessary for transendothelial migration of T cells. Blood 102:3675–3683 Epub 2003 Jul 3631PubMedCrossRef

84.

Vestweber D (2007) Adhesion and signaling molecules controlling the transmigration of leukocytes through endothelium. Immunol Rev 218:178–196PubMedCrossRef

85.

Carman CV, Springer TA (2008) Trans-cellular migration: cell-cell contacts get intimate. Curr Opin Cell Biol 20(5):533–540PubMedCrossRef

86.

Barreiro O, Yanez-Mo M, Serrador JM et al (2002) Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J Cell Biol 157:1233–1245PubMedCrossRef

87.

Carman CV, Springer TA (2004) A transmigratory cup in leukocyte diapedesis both through individual vascular endothelial cells and between them. J Cell Biol 167:377–388PubMedCrossRef

88.

Cross AH, Raine CS (1991) Central nervous system endothelial cell-polymorphonuclear cell interactions during autoimmune demyelination. American 139(6):1401–1409

89.

Engelhardt B, Wolburg H (2004) Mini-review: transendothelial migration of leukocytes: through the front door or around the side of the house? Eur J Immunol 34(11):2955–2963PubMedCrossRef

90.

Wolburg H, Wolburg-Buchholz K, Engelhardt B (2005) Diapedesis of mononuclear cells across cerebral venules during experimental autoimmune encephalomyelitis leaves tight junctions intact. Acta Neuropathol (Berl) 109(2):181–190CrossRef

91.

Geberhiwot T, Assefa D, Kortesmaa J et al (2001) Laminin-8 (alpha4beta1gamma1) is synthesized by lymphoid cells, promotes lymphocyte migration and costimulates T cell proliferation. J Cell Sci 114(Pt 2):423–433PubMed

92.

Thyboll J, Kortesmaa J, Cao R et al (2002) Deletion of the laminin alpha4 chain leads to impaired microvessel maturation. Mol Cell Biol 22(4):1194–1202PubMedCrossRef

93.

Colognato H, Yurchenco PD (2000) Form and function: the laminin family of heterotrimers. Dev Dyn 218(2):213–234PubMedCrossRef

94.

Yurchenco PD, Smirnov S, Mathus T (2002) Analysis of basement membrane self-assembly and cellular interactions with native and recombinant glycoproteins. Methods Cell Biol 69:111–144PubMedCrossRef

95.

Graesser D, Mahooti S, Madri JA (2000) Distinct roles for matrix metalloproteinase-2 and alpha4 integrin in autoimmune T cell extravasation and residency in brain parenchyma during experimental autoimmune encephalomyelitis. J Neuroimmunol 109(2):121–131PubMedCrossRef

96.

Dubois B, Masure S, Hurtenbach U et al (1999) Resistance of young gelatinase B-deficient mice to experimental autoimmune encephalomyelitis and necrotizing tail lesions. J Clin Invest 104:1507–1515PubMedCrossRef

97.

Kieseier BC, Clements JM, Pischel HB et al (1998) Matrix metalloproteinases MMP-9 and MMP-7 are expressed in experimental autoimmune neuritis and the Guillain-Barre syndrome. Annals 43(4):427–434

98.

Toft-Hansen H, Nuttall RK, Edwards DR, Owens T (2004) Key metalloproteinases are expressed by specific cell types in experimental autoimmune encephalomyelitis. J Immunol 173(8):5209–5218PubMed

99.

Toft-Hansen H, Babcock AA, Millward JM, Owens T (2007) Downregulation of membrane type-matrix metalloproteinases in the inflamed or injured central nervous system. J Neuroinflammation 4:24PubMedCrossRef

100.

Nygardas P, Hinkkanen A (2002) Up-regulation of MMP-8 and MMP-9 activity in the BALB/c mouse spinal cord correlates with the severity of experimental autoimmune encephalomyelitis. Clin Exp Immunol 128:245–254PubMedCrossRef

101.

Gijbels K, Galardy RE, Steinman L (1994) Reversal of experimental autoimmune encephalomyelitis with a hydroxamate inhibitor of matrix metalloproteases. J Clin Invest 94(6):2177–2182PubMedCrossRef

102.

Morini M, Roccatagliata L, Dell’Eva R et al (2004) Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis. J Neuroimmunol 148(1–2):146–153PubMedCrossRef

103.

Parks WC, Wilson CL, Lopez-Boado YS (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nature reviews 4(8):617–629PubMedCrossRef

104.

McCawley LJ, Matrisian LM (2001) Matrix metalloproteinases: they’re not just for matrix anymore!. Curr Opin Cell Biol 13:534–540PubMedCrossRef

105.

Dean RA, Overall CM (2007) Proteomics discovery of metalloproteinase substrates in the cellular context by iTRAQ labeling reveals a diverse MMP-2 substrate degradome. Mol Cell Proteomics 6(4):611–623PubMedCrossRef

106.

Overall CM, Blobel CP (2007) In search of partners: linking extracellular proteases to substrates. Nature reviews 8(3):245–257PubMedCrossRef

107.

Talts JF, Andac Z, Göhring W, Brancaccio A, Timpl R (1999) Binding of G domains of laminin alpha 1 and alpha 2 chains and perlecan to heparin, sulfatides, alpha-dystroglycan and several extracellular matrix proteins. EMBO J 18:863–870PubMedCrossRef

108.

Toft-Hansen H, Buist R, Sun XJ et al (2006) Metalloproteinases control brain inflammation induced by pertussis toxin in mice overexpressing the chemokine CCL2 in the central nervous system. J Immunol 177(10):7242–7249PubMed

109.

Betz LA, Goldstein GW, Katzman R (1989) Blood-brain-cerebrospinal fluid barriers. In: Siegel GJ (ed) Basic neurochemistry: molecular, cellular, and medical aspects. Raven, New York, pp 591–606

110.

Wolburg H, Wolburg-Buchholz K, Liebner S, Engelhardt B (2001) Claudin-1, claudin-2 and claudin-11 are present in tight junctions of choroid plexus epithelium of the mouse. Neurosci Lett 307(2):77–80PubMedCrossRef

111.

Bronstein JM, Tiwari-Woodruff S, Buznikov AG, Stevens DB (2000) Involvement of OSP/Claudin-11 in oligodendrocyte membrane interactions: role in biology and disease [review]. J Neurosci Res 59(6):706–711PubMedCrossRef

112.

de Lange EC (2004) Potential role of ABC transporters as a detoxification system at the blood-CSF barrier. Adv Drug Deliv Rev 56(12):1793–1809PubMedCrossRef

113.

Liao KK, Lu KS (1993) Cast-model and scanning electron microscopy of the rat brain ventricular system. Kao Hsiung I Hsueh Ko Hsueh Tsa Chih 9(6):328–337PubMed

114.

Ling EA, Kaur C, Lu J (1998) Origin, nature and some functional considerations of intraventrucular macrophages, with special reference to the epiplexus cells. Microsc Res Tech 41:43–56PubMedCrossRef

115.

Lu J, Kaur C, Ling EA (1994) Up-regulation of surface antigens on epiplexus cells in postnatal rats following intraperitoneal injections of lipopolysaccaride. Neurosci 63:1169–1178CrossRef

116.

Wolburg K, Gerhardt H, Schulz M, Wolburg H, Engelhardt B (1999) Ultrastructural localization of adhesion molecules in the healthy and inflamed choroid plexus of the mouse. Cell Tissue Res 296(2):259–269PubMedCrossRef

117.

Steffen BJ, Breier G, Butcher EC, Schulz M, Engelhardt B (1996) ICAM-1, VCAM-1, and MAdCAM-1 are expressed on choroid plexus epithelium but not endothelium and mediate binding of lymphocytes in vitro. American 148(6):1819–1838

118.

Kivisakk P, Mahad DJ, Callahan MK et al (2005) Human cerebrospinal fluid central memory CD4+ T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. Proc Natl Acad Sci U S A 100:8389–8394 Epub 2003 Jun 8326CrossRef

119.

Reboldi A, Coisne C, Baumjohann D et al (2009) C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE. Nat Immunol 10(5):514–523PubMedCrossRef

120.

Dickeson SK, Mathis NL, Rahman M, Bergelson JM, Santoro SA (1999) Determinants of ligand binding specificity of the alpha(1)beta(1) and alpha(2)beta(1) integrins. J Biol Chem 274(45):32182–32191PubMedCrossRef

121.

Eble JA, Kassner A, Niland S, et al (2006) Collagen XVI harbors an integrin alpha1 beta1 recognition site in its C-terminal domains. J Biol Chem 28 (35):25745–25756CrossRef

122.

Eble JA (2005) Collagen-binding integrins as pharmaceutical targets. Curr Pharm Des 11(7):867–880PubMedCrossRef

123.

Wagner S, Gardner H (2000) Modes of regulation of laminin-5 production by rat astrocytes. Neurosci Lett 284(1–2):105–108PubMedCrossRef

Titel: The blood–brain and the blood–cerebrospinal fluid barriers: function and dysfunction
verfasst von: Britta Engelhardt
Lydia Sorokin
Publikationsdatum: 01.11.2009
Verlag: Springer-Verlag
Erschienen in: Seminars in Immunopathology / Ausgabe 4/2009
Print ISSN: 1863-2297
Elektronische ISSN: 1863-2300
DOI: https://doi.org/10.1007/s00281-009-0177-0

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2009

Role of microglia in neuronal degeneration and regeneration

Central nervous system vasculitis

Encephalitis and epilepsy

Progress in understanding inflammatory and autoimmune diseases of the central nervous system

Modeling multiple sclerosis in laboratory animals