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Topological Aspects of the Blood–Brain and Blood–Cerebrospinal Fluid Barriers and Their Relevance in Inflammation

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The Blood Brain Barrier and Inflammation

Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

In both multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis, the blood–brain barrier (BBB) is known to be compromised at the level of postcapillary venules. In addition to this segment of blood circulation, recent research has focused on the role of the choroid plexus (CP), which is crossed by encephalitogenic T-cells to enter the cerebrospinal fluid (CSF) and to reach the subarachnoid space (SAS). Here, cytokines can activate local antigen-presenting cells to enhance the transmission of inflammatory cells from the subpial vasculature into the SAS to evoke meningitis- and encephalitis-related diseases. However, overcoming the endothelium in the postcapillary venules and the epithelium in the CP do not seem to be the only mechanisms in the induction process of inflammation. Rather, as there is continuity between the stroma of the CP and the SAS, this continuity could serve as a direct pathway for inflammatory cells. In this review, we describe the morphological properties of barrier-related cells in both the brain vasculature and the CP to draw attention to possible mechanisms of the processes of inflammation in the central nervous system. We focus on permeability-related structures, such as tight junctions in endothelial cells of the BBB and in endothelial and epithelial cells of the CP, which represent the main site of the blood–CSF barrier proper.

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Literature

  1. Abadier M, Haghayegh Jahromi N, Cardoso Alves L, Boscacci R, Vestweber D, Barnum S, Deutsch U, Engelhardt B, Lyck R (2015) Cell surface levels of endothelial ICAM-1 influence the transcellular or paracellular T-cell diapedesis across the blood–brain barrier. Eur J Immunol 45:1043–1058

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. 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  CAS  PubMed  PubMed Central  Google Scholar 

  4. Alvarez JI, Saint-Laurent O, Godschalk A, Terouz S, Briels C, Larouche S, Bourbonniere L, Larochelle C, Prat A (2015) Focal disturbances in the blood–brain barrier are associated with formation of neuroinflammatory lesions. Neurobiol Dis 74:14–24

    Article  CAS  PubMed  Google Scholar 

  5. Amiry-Moghaddam M, Ottersen OP (2003) The molecular basis of water transport in the brain. Nat Rev Neurosci 4:991–1001

    Article  CAS  PubMed  Google Scholar 

  6. Androdias G, Reynolds R, Chanal M, Ritleng C, Confavreux C, Nataf S (2010) Meningeal T cells associate with diffuse axonal loss in multiple sclerosis spinal cords. Ann Neurol 68:465–476

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  8. Bauer HC, Krizbai IA, Bauer H, Traweger A (2014) “You Shall Not Pass”-tight junctions of the blood brain barrier. Front Neurosci 8:392

    Article  PubMed  PubMed Central  Google Scholar 

  9. Becher B, Bechmann I, Greter M (2006) Antigen presentation in autoimmunity and CNS inflammation: how T lymphocytes recognize the brain. J Mol Med 84:532–543

    Article  CAS  PubMed  Google Scholar 

  10. Benfenati V, Ferroni S (2010) Water transport between CNS compartments: functional and molecular interactions between aquaporins and ion channels. Neuroscience 168:926–940

    Article  CAS  PubMed  Google Scholar 

  11. Bennett J, Basivireddy J, Kollar A, Biron KE, Reickmann P, Jefferies WA, McQuaid S (2010) Blood–brain barrier disruption and enhanced vascular permeability in the multiple sclerosis model EAE. J Neuroimmunol 229:180–191

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Carman CV, Sage PT, Sciuto TE, de la Fuente MA, Geha RS, Ochs HD, Dvorak HF, Dvorak AM, Springer TA (2007) Transcellular diapedesis is initiated by invasive podosomes. Immunity 26:784–797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Choi SR, Howell OW, Carassiti D, Magliozzi R, Gveric D, Muraro PA, Nicholas R, Roncaroli F, Reynolds R (2012) Meningeal inflammation plays a role in the pathology of primary progressive multiple sclerosis. Brain 135:2925–2937

    Article  PubMed  Google Scholar 

  15. Duchi S, Ovadia H, Touitou E (2013) Nasal administration of drugs as a new non-invasive strategy for efficient treatment of multiple sclerosis. J Neuroimmunol 258:32–40

    Article  CAS  PubMed  Google Scholar 

  16. Ehrlich P (1885) Das Sauerstoff-Bedürfnis des Organismus. Eine farbenanalytische Studie. PhD thesis, Herschwal, Berlin, p 69–72

    Google Scholar 

  17. Eilert-Olsen M, Haj-Yasein NN, Vindedal GF, Enger R, Gundersen GA, Hoddevik EH, Petersen PH, Haug FM, Skare O, Adams ME, Froehner SC, Burkhardt JM, Thoren AE, Nagelhus EA (2012) Deletion of aquaporin-4 changes the perivascular glial protein scaffold without disrupting the brain endothelial barrier. Glia 60:432–440

    Article  PubMed  Google Scholar 

  18. Engelhardt B (2010) T cell migration into the central nervous system during health and disease: different molecular keys allow access to different central nervous system compartments. Clin exp Neuroimmunol 1:79–93

    Article  CAS  Google Scholar 

  19. Engelhardt B, Ransohoff RM (2012) Capture, crawl, cross: the T cell code to breach the blood–brain barriers. Trends Immunol 33:579–589

    Article  CAS  PubMed  Google Scholar 

  20. 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 34:2955–2963

    Article  CAS  PubMed  Google Scholar 

  21. Errede M, Girolamo F, Ferrara G, Strippoli M, Morando S, Boldrin V, Rizzi M, Uccelli A, Perris R, Bendotti C, Salmona M, Roncali L, Virgintino D (2012) Blood–brain barrier alterations in the cerebral cortex in experimental autoimmune encephalomyelitis. J Neuropathol Exp Neurol 71:840–854

    Article  CAS  PubMed  Google Scholar 

  22. Esser S, Wolburg K, Wolburg H, Breier G, Kurzchalia T, Risau W (1998) Vascular endothelial growth factor induces endothelial fenestrations in vitro. J Cell Biol 140:947–959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Friese MA, Fugger L (2005) Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy? Brain 128:1747–1763

    Article  PubMed  Google Scholar 

  24. Furuse M, Fujita K, Hiiragi T, Fujimoto K, Tsukita S (1998) Claudin-1 and −2: novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin. J Cell Biol 141:1539–1550

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Furuse M, Sasaki H, Tsukita S (1999) Manner of interaction of heterogeneous claudin species within and between tight junction strands. J Cell Biol 147:891–903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gardner C, Magliozzi R, Durrenberger PF, Howell OW, Rundle J, Reynolds R (2013) Cortical grey matter demyelination can be induced by elevated pro-inflammatory cytokines in the subarachnoid space of MOG-immunized rats. Brain J Neurol 136:3596–3608

    Article  Google Scholar 

  27. Giacoppo S, Galuppo M, Iori R, De Nicola GR, Bramanti P, Mazzon E (2014) The protective effects of bioactive (RS)-glucoraphanin on the permeability of the mice blood–brain barrier following experimental autoimmune encephalomyelitis. Eur Rev Med Pharmacol Sci 18:194–204

    CAS  PubMed  Google Scholar 

  28. Goldmann EE (1913) Vitalfärbungen am Zentralnervensystem. Beitrag zur Physio-Pathologie des Plexus Choroideus und der Hirnhäute. Abh Preuss Akad Wiss Physik-Mathematik 1:1–60

    Google Scholar 

  29. Greenwood J, Heasman SJ, Alvarez JI, Prat A, Lyck R, Engelhardt B (2011) Review: leucocyte-endothelial cell crosstalk at the blood–brain barrier: a prerequisite for successful immune cell entry to the brain. Neuropathol Appl Neurobiol 37:24–39

    Article  CAS  PubMed  Google Scholar 

  30. Greter M, Heppner FL, Lemos MP, Odermatt BM, Goebels N, Laufer T, Noelle RJ, Becher B (2005) Dendritic cells permit immune invasion of the CNS in an animal model of multiple sclerosis. Nat Med 11:328–334

    Article  CAS  PubMed  Google Scholar 

  31. Gunzel D, Fromm M (2012) Claudins and other tight junction proteins. Compr Physiol 2:1819–1852

    PubMed  Google Scholar 

  32. Haseloff RF, Dithmer S, Winkler L, Wolburg H, Blasig IE (2015) Transmembrane proteins of the tight junctions at the blood–brain barrier: structural and functional aspects. Semin Cell Dev Biol 38:16–25

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  34. Howell OW, Reeves CA, Nicholas R, Carassiti D, Radotra B, Gentleman SM, Serafini B, Aloisi F, Roncaroli F, Magliozzi R, Reynolds R (2011) Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain 134:2755–2771

    Article  PubMed  Google Scholar 

  35. Iliff JJ, Wang M, Liao Y, Plogg BA, Peng W, Gundersen GA, Benveniste H, Vates GE, Deane R, Goldman SA, Nagelhus EA, Nedergaard M (2012) A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid beta. Sci Transl Med 4:147ra111

    Article  PubMed  PubMed Central  Google Scholar 

  36. Illum L (2000) Transport of drugs from the nasal cavity to the central nervous system. Eur J Pharm Sci Off J Eur Fed Pharm Sci 11:1–18

    CAS  Google Scholar 

  37. Jackson RT, Tigges J, Arnold W (1979) Subarachnoid space of the CNS, nasal mucosa, and lymphatic system. Arch Otolaryngol 105:180–184

    Article  CAS  PubMed  Google Scholar 

  38. Kermode AG, Thompson AJ, Tofts P, MacManus DG, Kendall BE, Kingsley DP, Moseley IF, Rudge P, McDonald WI (1990) Breakdown of the blood–brain barrier precedes symptoms and other MRI signs of new lesions in multiple sclerosis. Pathogenetic and clinical implications. Brain 113(Pt 5):1477–1489

    Article  PubMed  Google Scholar 

  39. Kirk J, Plumb J, Mirakhur M, McQuaid S (2003) Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood–brain barrier leakage and active demyelination. J Pathol 201:319–327

    Article  PubMed  Google Scholar 

  40. Kivisakk P, Imitola J, Rasmussen S, Elyaman W, Zhu B, Ransohoff RM, Khoury SJ (2009) Localizing central nervous system immune surveillance: meningeal antigen-presenting cells activate T cells during experimental autoimmune encephalomyelitis. Ann Neurol 65:457–469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kooij G, Kopplin K, Blasig R, Stuiver M, Koning N, Goverse G, van der Pol SM, van Het Hof B, Gollasch M, Drexhage JA, Reijerkerk A, Meij IC, Mebius R, Willnow TE, Muller D, Blasig IE, de Vries HE (2014) Disturbed function of the blood-cerebrospinal fluid barrier aggravates neuro-inflammation. Acta Neuropathol 128:267–277

    Article  CAS  PubMed  Google Scholar 

  42. Kutzelnigg A, Lassmann H (2014) Pathology of multiple sclerosis and related inflammatory demyelinating diseases. Handb Clin Neurol 122:15–58

    Article  PubMed  Google Scholar 

  43. Lanz TV, Becker S, Osswald M, Bittner S, Schuhmann MK, Opitz CA, Gaikwad S, Wiestler B, Litzenburger UM, Sahm F, Ott M, Iwantscheff S, Grabitz C, Mittelbronn M, von Deimling A, Winkler F, Meuth SG, Wick W, Platten M (2013) Protein kinase Cbeta as a therapeutic target stabilizing blood–brain barrier disruption in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 110:14735–14740

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lassmann H, Wekerle H (2005) The pathology of multiple sclerosis. In: Compston A (ed) McAlpine’s multiple sclerosis. Elsevier Churchill Livingstone, Edinburgh, pp 557–599

    Google Scholar 

  45. Leech S, Kirk J, Plumb J, McQuaid S (2007) Persistent endothelial abnormalities and blood–brain barrier leak in primary and secondary progressive multiple sclerosis. Neuropathol Appl Neurobiol 33:86–98

    Article  CAS  PubMed  Google Scholar 

  46. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202:473–477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106–2112

    Article  CAS  PubMed  Google Scholar 

  48. Lippoldt A, Liebner S, Andbjer B, Kalbacher H, Wolburg H, Haller H, Fuxe K (2000) Organization of choroid plexus epithelial and endothelial cell tight junctions and regulation of claudin-1, −2 and −5 expression by protein kinase C. Neuroreport 11:1427–1431

    Article  CAS  PubMed  Google Scholar 

  49. Magliozzi R, Howell O, Vora A, Serafini B, Nicholas R, Puopolo M, Reynolds R, Aloisi F (2007) Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology. Brain 130:1089–1104

    Article  PubMed  Google Scholar 

  50. Mathiisen TM, Lehre KP, Danbolt NC, Ottersen OP (2010) The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia 58:1094–1103

    Article  PubMed  Google Scholar 

  51. McMahan UJ (1990) The agrin hypothesis. Cold Spring Harb Symp Quant Biol 55:407–418

    Article  CAS  PubMed  Google Scholar 

  52. Mühleisen H, Wolburg H, Betz E (1989) Freeze-fracture analysis of endothelial cell membranes in rabbit carotid arteries subjected to short-term atherogenic stimuli. Virchows Arch B Cell Pathol Incl Mol Pathol 56:413–417

    Article  PubMed  Google Scholar 

  53. Muldoon LL, Alvarez JI, Begley DJ, Boado RJ, Del Zoppo GJ, Doolittle ND, Engelhardt B, Hallenbeck JM, Lonser RR, Ohlfest JR, Prat A, Scarpa M, Smeyne RJ, Drewes LR, Neuwelt EA (2013) Immunologic privilege in the central nervous system and the blood–brain barrier. J Cereb Blood Flow Metab 33:13–21

    Article  CAS  PubMed  Google Scholar 

  54. Nagy Z, Peters H, Huttner I (1984) Fracture faces of cell junctions in cerebral endothelium during normal and hyperosmotic conditions. Lab Invest 50:313–322

    CAS  PubMed  Google Scholar 

  55. Nedergaard M (2013) Neuroscience. Garbage truck of the brain. Sci 340:1529–1530

    Article  CAS  Google Scholar 

  56. Noell S, Fallier-Becker P, Beyer C, Kroger S, Mack AF, Wolburg H (2007) Effects of agrin on the expression and distribution of the water channel protein aquaporin-4 and volume regulation in cultured astrocytes. Eur J Neurosci 26:2109–2118

    Article  PubMed  Google Scholar 

  57. Noell S, Fallier-Becker P, Deutsch U, Mack AF, Wolburg H (2009) Agrin defines polarized distribution of orthogonal arrays of particles in astrocytes. Cell Tissue Res 337:185–195

    Article  CAS  PubMed  Google Scholar 

  58. Noell S, Wolburg-Buchholz K, Mack AF, Beedle AM, Satz JS, Campbell KP, Wolburg H, Fallier-Becker P (2011) Evidence for a role of dystroglycan regulating the membrane architecture of astroglial endfeet. Eur J Neurosci 33:2179–2186

    Article  PubMed  PubMed Central  Google Scholar 

  59. Noseworthy JH, Lucchinetti C, Rodriguez M, Weinshenker BG (2000) Multiple sclerosis. N Engl J Med 343:938–952

    Article  CAS  PubMed  Google Scholar 

  60. Obermeier B, Daneman R, Ransohoff RM (2013) Development, maintenance and disruption of the blood–brain barrier. Nat Med 19:1584–1596

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Owens T, Bechmann I, Engelhardt B (2008) Perivascular spaces and the two steps to neuroinflammation. J Neuropathol Exp Neurol 67:1113–1121

    Article  PubMed  Google Scholar 

  62. Pfeiffer F, Schafer J, Lyck R, Makrides V, Brunner S, Schaeren-Wiemers N, Deutsch U, Engelhardt B (2011) Claudin-1 induced sealing of blood–brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis. Acta Neuropathol 122:601–614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Piontek J, Fritzsche S, Cording J, Richter S, Hartwig J, Walter M, Yu D, Turner JR, Gehring C, Rahn HP, Wolburg H, Blasig IE (2011) Elucidating the principles of the molecular organization of heteropolymeric tight junction strands. Cell Mol Life Sci 68:3903–3918

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Pollinger B, Krishnamoorthy G, Berer K, Lassmann H, Bosl MR, Dunn R, Domingues HS, Holz A, Kurschus FC, Wekerle H (2009) Spontaneous relapsing-remitting EAE in the SJL/J mouse: MOG-reactive transgenic T cells recruit endogenous MOG-specific B cells. J Exp Med 206:1303–1316

    Article  PubMed  PubMed Central  Google Scholar 

  65. Ransohoff RM, Engelhardt B (2012) The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol 12:623–635

    Article  CAS  PubMed  Google Scholar 

  66. Rash JE, Yasumura T, Hudson CS, Agre P, Nielsen S (1998) Direct immunogold labeling of aquaporin-4 in square arrays of astrocyte and ependymocyte plasma membranes in rat brain and spinal cord. Proc Natl Acad Sci U S A 95:11981–11986

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Reboldi A, Coisne C, Baumjohann D, Benvenuto F, Bottinelli D, Lira S, Uccelli A, Lanzavecchia A, Engelhardt B, Sallusto F (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 10:514–523

    Article  CAS  PubMed  Google Scholar 

  68. 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  PubMed Central  Google Scholar 

  69. Reichenbach A, Wolburg H (2013) Astrocytes and ependymal cells. Kettenmann H, Ransom BR (eds) Neuroglia, 3rd edn. Oxford University Press, Oxford, p 35–49

    Google Scholar 

  70. Rolak LA (2003) Multiple sclerosis: it’s not the disease you thought it was. Clin Med Res 1:57–60

    Article  PubMed  PubMed Central  Google Scholar 

  71. Russi AE, Brown MA (2015) The meninges: new therapeutic targets for multiple sclerosis. Translational Res J Lab Clin Med 165:255–269

    Article  Google Scholar 

  72. Saunders NR, Dreifuss JJ, Dziegielewska KM, Johansson PA, Habgood MD, Mollgard K, Bauer HC (2014) The rights and wrongs of blood–brain barrier permeability studies: a walk through 100 years of history. Front Neurosci 8:404

    Article  PubMed  PubMed Central  Google Scholar 

  73. Sayed BA, Christy AL, Walker ME, Brown MA (2010) Meningeal mast cells affect early T cell central nervous system infiltration and blood–brain barrier integrity through TNF: a role for neutrophil recruitment? J Immunol 184:6891–6900

    Article  CAS  PubMed  Google Scholar 

  74. Serafini B, Rosicarelli B, Magliozzi R, Stigliano E, Aloisi F (2004) Detection of ectopic B-cell follicles with germinal centers in the meninges of patients with secondary progressive multiple sclerosis. Brain Pathol 14:164–174

    Article  PubMed  Google Scholar 

  75. Shultz LD, Ishikawa F, Greiner DL (2007) Humanized mice in translational biomedical research. Nat Rev Immunol 7:118–130

    Article  CAS  PubMed  Google Scholar 

  76. Steiner E, Enzmann GU, Lyck R, Lin S, Ruegg MA, Kroger S, Engelhardt B (2014) The heparan sulfate proteoglycan agrin contributes to barrier properties of mouse brain endothelial cells by stabilizing adherens junctions. Cell Tissue Res 358:465–479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Steinmann U, Borkowski J, Wolburg H, Schroppel B, Findeisen P, Weiss C, Ishikawa H, Schwerk C, Schroten H, Tenenbaum T (2013) Transmigration of polymorphnuclear neutrophils and monocytes through the human blood-cerebrospinal fluid barrier after bacterial infection in vitro. J Neuroinflammation 10:31

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Tenenbaum T, Papandreou T, Gellrich D, Friedrichs U, Seibt A, Adam R, Wewer C, Galla HJ, Schwerk C, Schroten H (2009) Polar bacterial invasion and translocation of Streptococcus suis across the blood-cerebrospinal fluid barrier in vitro. Cell Microbiol 11:323–336

    Article  CAS  PubMed  Google Scholar 

  79. Tietz S, Engelhardt B (2015) Brain barriers: crosstalk between complex tight junctions and adherens junctions. J Cell Biol 209:493–506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. van Horssen J, Brink BP, de Vries HE, van der Valk P, Bo L (2007) The blood–brain barrier in cortical multiple sclerosis lesions. J Neuropathol Exp Neurol 66:321–328

    Article  PubMed  Google Scholar 

  81. Varrin-Doyer M, Spencer CM, Schulze-Topphoff U, Nelson PA, Stroud RM, Cree BA, Zamvil SS (2012) Aquaporin 4-specific T cells in neuromyelitis optica exhibit a Th17 bias and recognize Clostridium ABC transporter. Ann Neurol 72:53–64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Wang XS, Fang HL, Chen Y, Liang SS, Zhu ZG, Zeng QY, Li J, Xu HQ, Shao B, He JC, Hou ST, Zheng RY (2014) Idazoxan reduces blood–brain barrier damage during experimental autoimmune encephalomyelitis in mouse. Eur J Pharmacol 736:70–76

    Article  CAS  PubMed  Google Scholar 

  83. Warth A, Kroger S, Wolburg H (2004) Redistribution of aquaporin-4 in human glioblastoma correlates with loss of agrin immunoreactivity from brain capillary basal laminae. Acta Neuropathol 107:311–318

    Article  CAS  PubMed  Google Scholar 

  84. Wekerle H, Flugel A, Fugger L, Schett G, Serreze D (2012) Autoimmunity’s next top models. Nat Med 18:66–70

    Article  CAS  PubMed  Google Scholar 

  85. Wolburg-Buchholz K, Mack AF, Steiner E, Pfeiffer F, Engelhardt B, Wolburg H (2009) Loss of astrocyte polarity marks blood–brain barrier impairment during experimental autoimmune encephalomyelitis. Acta Neuropathol 118:219–233

    Article  CAS  PubMed  Google Scholar 

  86. 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 

  87. Wolburg H, Mack A (2014) Comment on the topology of mammalian blood-cerebrospinal fluid barriers. Neurol Psych Brain Res 20:70–72

    Article  Google Scholar 

  88. Wolburg H, Neuhaus J, Kniesel U, Krauss B, Schmid EM, Ocalan M, Farrell C, Risau W (1994) Modulation of tight junction structure in blood–brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes. J Cell Sci 107(Pt 5):1347–1357

    CAS  PubMed  Google Scholar 

  89. 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 

  90. Wolburg H, Noell S, Wolburg-Buchholz K, Mack A, Fallier-Becker P (2009) Agrin, aquaporin-4, and astrocyte polarity as an important feature of the blood–brain barrier. Neuroscientist 15:180–193

    Article  CAS  PubMed  Google Scholar 

  91. Wolburg H, Paulus W (2010) Choroid plexus: biology and pathology. Acta Neuropathol 119:75–88

    Article  PubMed  Google Scholar 

  92. 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 109:181–190

    Article  PubMed  Google Scholar 

  93. Wolburg H, Wolburg-Buchholz K, Fallier-Becker P, Noell S, Mack AF (2011) Structure and functions of aquaporin-4-based orthogonal arrays of particles. Int Rev Cell Mol Biol 287:1–41

    Article  CAS  PubMed  Google Scholar 

  94. Wolburg H, Wolburg-Buchholz K, Kraus J, Rascher-Eggstein G, Liebner S, Hamm S, Duffner F, Grote EH, Risau W, Engelhardt B (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 105:586–592

    CAS  PubMed  Google Scholar 

  95. Wolburg H, Wolburg-Buchholz K, Reichenbach A, Mack AF (2015) Ependymal cells. Reference module in biomedical sciences. http://dx.doi.org/10.1016/B978-0-12-801238-3.04586-4

  96. Yousif LF, Di Russo J, Sorokin L (2013) Laminin isoforms in endothelial and perivascular basement membranes. Cell Adh Migr 7:101–110

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This review was broadly written on the basis of the former collaboration between the group of HW and that of Prof Dr Britta Engelhardt, Theodor Kocher-Institute of the University of Berne, Switzerland. In particular, Dr Karen Wolburg-Buchholz has contributed essential results cited in this book chapter. FP was formerly member of the group of Prof Engelhardt and was financially supported by the DFG (grant PF574/2-1) and the Integrating Project JUSTBRAIN (EU, FP7 No. HEALTH-2009-241861).

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Authors and Affiliations

  1. Werner Reichardt Centre for Integrative Neuroscience (CIN), University of Tübingen, Tübingen, Germany

    Friederike Pfeiffer

  2. Institute of Clinical Anatomy and Cell Analysis, University of Tübingen, Tübingen, Germany

    Andreas F. Mack

  3. Institute of Pathology and Neuropathology, University of Tübingen, Liebermeisterstraße 8, 72076, Tübingen, Germany

    Hartwig Wolburg

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  1. Friederike Pfeiffer
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  3. Hartwig Wolburg
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Correspondence to Hartwig Wolburg .

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  1. Theodor Kocher Institute, University of Bern, Bern, Switzerland

    Ruth Lyck

  2. Theodor Kocher Institute, University of Bern, Bern, Switzerland

    Gaby Enzmann

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Pfeiffer, F., Mack, A.F., Wolburg, H. (2017). Topological Aspects of the Blood–Brain and Blood–Cerebrospinal Fluid Barriers and Their Relevance in Inflammation. In: Lyck, R., Enzmann, G. (eds) The Blood Brain Barrier and Inflammation. Progress in Inflammation Research. Springer, Cham. https://doi.org/10.1007/978-3-319-45514-3_2

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  • DOI: https://doi.org/10.1007/978-3-319-45514-3_2

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-45512-9

  • Online ISBN: 978-3-319-45514-3

  • eBook Packages: MedicineMedicine (R0)

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