Breaking and building the wall: The biology of the blood-brain barrier in health and disease

Swiss Medical Weekly

Volumn 143, Issue , 2013, Pages

  Keller, Annika ^a,b  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^b UPPSALA UNIVERSITY   (Sweden)

Author keywords

Astrocytes; Blood brain barrier; Brain pathology; Endothelium; Neurovascular unit; Pericytes

Indexed keywords

BONE MORPHOGENETIC PROTEIN RECEPTOR 1; CLAUDIN 1; CLAUDIN 3; CLAUDIN 5; JUNCTIONAL ADHESION MOLECULE; MEMBRANE PROTEIN; MONOCARBOXYLATE TRANSPORTER; MULTIDRUG RESISTANCE PROTEIN; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 2; MULTIDRUG RESISTANCE PROTEIN 4; MULTIDRUG RESISTANCE PROTEIN 5; PLATELET DERIVED GROWTH FACTOR BETA RECEPTOR; PRESENILIN 1; VASCULOTROPIN A; WNT PROTEIN; ZONULA OCCLUDENS PROTEIN; DEATH RECEPTOR; DEATH RECEPTOR 6; GLUCOSE TRANSPORTER 1; MONOCARBOXYLATE TRANSPORTER 1; NOTCH3 RECEPTOR; PLATELET DERIVED GROWTH FACTOR B; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR FAMILY RECEPTOR TROY; TUMOR NECROSIS FACTOR RECEPTOR; UNCLASSIFIED DRUG;

ACUTE LIVER FAILURE; ASTROCYTE; BASEMENT MEMBRANE; BLOOD BRAIN BARRIER; BRAIN BLOOD VESSEL; BRAIN DEVELOPMENT; CARBON MONOXIDE INTOXICATION; CELL JUNCTION; CEREBROVASCULAR DISEASE; COGNITIVE DEFECT; EMBRYO DEVELOPMENT; FAHR DISEASE; HUMAN; LOSS OF FUNCTION MUTATION; MACROPHAGE; MICROGLIA; NONHUMAN; PERICYTE; POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME; REVIEW; TRANSCYTOSIS; VASCULAR ENDOTHELIUM; VASCULAR SMOOTH MUSCLE; WNT SIGNALING PATHWAY; ANGIOGENESIS; AUTOSOMAL DOMINANT DISORDER; BRAIN CALCIFICATION; CADASIL; CELL DIFFERENTIATION; CELL FUNCTION; CELL MIGRATION; DEGENERATIVE DISEASE; ENDOTHELIUM CELL; HOMEOSTASIS; HYPOXIA; IDIOPATHIC BASAL GANGLIA CALCIFICATION; IDIOPATHIC DISEASE; METABOLISM; NEUROVASCULAR UNIT; PATHOGENESIS; PERIVASCULAR MACROPHAGE; POSTOPERATIVE COGNITIVE DYSFUNCTION; SIGNAL TRANSDUCTION; SMOOTH MUSCLE FIBER; VASCULAR SMOOTH MUSCLE CELL; VASCULARIZATION; BRAIN; PATHOPHYSIOLOGY; PHYSIOLOGY;

ASTROCYTES; BLOOD-BRAIN BARRIER; BRAIN; ENDOTHELIUM, VASCULAR; HUMANS; INTERCELLULAR JUNCTIONS; PERICYTES;

EID: 84887885093     PISSN: 14247860     EISSN: 14243997     Source Type: Journal    
DOI: 10.4414/smw.2013.13892     Document Type: Review

References (99)

1. Abbott NJ. Dynamics of cns barriers: Evolution, differentiation, and modulation. Cell Mol Neurobiol. 2005;25(1):5-23.
2. Abbott N, Lane N, Bundgaard M. The blood-brain interface in invertebrates. Ann N Y Acad Sci. 1986;481:20-42.
3. Ruhrberg C, Bautch V. Neurovascular development and links to disease. Cellular and molecular life sciences: CMLS. 2013;70(10):1675-84.
4. Tam S, Richmond D, Kaminker J, Modrusan Z, Martin-Mcnulty B, Cao T, et al. Death receptors dr6 and troy regulate brain vascular development. Developmental Cell. 2012;22(2):403-17.
5. Daneman R, Agalliu D, Zhou L, Kuhnert F, Kuo CJ, Barres BA. Wnt/ beta-catenin signaling is required for cns, but not non-cns, angiogenesis. Proc Natl Acad Sci U S A. 2009;106(2):641-6.
6. Stenman JM, Rajagopal J, Carroll TJ, Ishibashi M, Mcmahon J, Mcmahon AP. Canonical wnt signaling regulates organ-specific assembly and differentiation of cns vasculature. Science. 2008;322(5905):1247-50.
7. Mizee M, Wooldrik D, Lakeman K, Van Het Hof B, Drexhage J, Geerts D, et al. Retinoic acid induces blood-brain barrier development. J Neurosci. 2013;33(4):1660-71.
8. Wen P, De Gasperi R, Sosa M, Rocher A, Friedrich V, Hof P, et al. Selective expression of presenilin 1 in neural progenitor cells rescues the cerebral hemorrhages and cortical lamination defects in presenilin 1-null mutant mice. Development (Cambridge, England). 2005;132(17):3873-83.
9. Proctor J, Zang K, Wang D, Wang R, Reichardt L. Vascular development of the brain requires beta8 integrin expression in the neuroepithelium. J Neurosci. 2005;25(43):9940-8.
10. Arnold T, Ferrero G, Qiu H, Phan I, Akhurst R, Huang E, et al. Defective retinal vascular endothelial cell development as a consequence of impaired integrin αvβ8-mediated activation of transforming growth factor-β. J Neurosci. 2012;32(4):1197-206.
11. Armulik A, Genove G, Betsholtz C. Pericytes: Developmental, physiological, and pathological perspectives, problems, and promises. Developmental Cell. 2011;21(2):193-215.
12. Nguyen H-L, Lee Y, Shin J, Lee E, Park S, Mccarty, J, et al. Tgf-β signaling in endothelial cells, but not neuroepithelial cells, is essential for cerebral vascular development. Laboratory investigation; a journal of technical methods and pathology. 2011;91(11):1554-63.
13. Kuhnert F, Mancuso M, Shamloo A, Wang H-T, Choksi V, Florek M, et al. Essential regulation of cns angiogenesis by the orphan g protein-coupled receptor gpr124. Science (New York, NY). 2010;330(6006):985-9.
14. Anderson K, Pan L, Yang X-M, Hughes V, Walls J, Dominguez M, et al. Angiogenic sprouting into neural tissue requires gpr124, an orphan g protein-coupled receptor. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(7):2807-12.
15. Cullen M, Elzarrad M, Seaman S, Zudaire E, Stevens J, Yang M, et al. Gpr124, an orphan g protein-coupled receptor, is required for cns-specific vascularization and establishment of the blood-brain barrier. Proceedings of the National Academy of Sciences of the United States of America, 2011;108(14):5759-64.
16. Saunders NR, Habgood MD, Dziegielewska KM. Barrier mechanisms in the brain, ii. Immature brain. Clin Exp Pharmacol Physiol. 1999;26(2):85-91.
17. Neuwelt EA, Bauer B, Fahlke C, Fricker G, Iadecola C, Janigro D, et al. Engaging neuroscience to advance translational research in brain barrier biology. Nat Rev Neurosci. 2011;12(3):169-82.
18. Hobson B, Denekamp J. Endothelial proliferation in tumours and normal tissues: Continuous labelling studies. Br J Cancer. 1984;49(4):405-13.
19. Attwell D, Buchan A, Charpak S, Lauritzen M, Macvicar B, Newman E. Glial and neuronal control of brain blood flow. Nature. 2010;468(7321):232-43.
20. Chabriat H, Joutel A, Dichgans M, Tournier-Lasserve E, Bousser M-G. Cadasil. Lancet Neurol. 2009;8(7):643-53.
21. Liu H, Zhang W, Kennard S, Caldwell R, Lilly B. Notch3 is critical for proper angiogenesis and mural cell investment. Circ Res. 2010;107(7):860-70.
22. Armulik A, Abramsson A, Betsholtz C. Endothelial/pericyte interactions. Circ Res. 2005;97(6):512-23.
23. Zovein A, Luque A, Turlo K, Hofmann J, Yee K, Becker M, et al. Beta1 integrin establishes endothelial cell polarity and arteriolar lumen formation via a par3-dependent mechanism. Dev Cell. 2010;18(1):39-51.
24. Armulik A, Genové G, Mäe M, Nisancioglu M, Wallgard E, Niaudet C, et al. Pericytes regulate the blood-brain barrier. Nature. 2010. 468(7323):557-61.
25. Daneman R, Zhou L, Kebede AA, Barres BA. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature. 2010;468(7323):562- 6.
26. Keller A, Westenberger A, Sobrido M, García-Murias M, Domingo A, Sears R, et al. Mutations in the gene encoding pdgf-b cause brain calcifications in humans and mice. Nat Genet. 2013;45(9):1077-82.
27. Nicolas G, Pottier C, Maltête D, Coutant S, Rovelet-Lecrux A, Legallic S, et al. Mutation of the pdgfrb gene as a cause of idiopathic basal ganglia calcification. Neurology. 2013;80(2):181-7.
28. Manyam B. What is and what is not "fahr's disease". Parkinsonism & related disorders. 2005;11(2):73-80.
29. Miklossy J, Mackenzie I, Dorovini-Zis K, Calne D, Wszolek Z, Klegeris A, et al. Severe vascular disturbance in a case of familial brain calcinosis. Acta Neuropathol. 2005;109(6):643-53.
30. Livingston J, Stivaros S, Van Der Knaap M,Crow Y. Recognizable phenotypes associated with intracranial calcification. Dev Med Child Neurol. 2013;55(1):46-57.
31. Wolburg H, Noell S, Mack A, Wolburg-Buchholz K, Fallier-Becker P. Brain endothelial cells and the glio-vascular complex. Cell Tissue Res. 2009;335(1):75-96.
32. Molofsky A, Krencik R, Krenick R, Ullian E, Tsai H-H, Deneen B, et al. Astrocytes and disease: A neurodevelopmental perspective. Genes Dev. 2012;26(9):891-907.
33. Landis DM, Reese TS. Membrane structure in mammalian astrocytes: A review of freeze-fracture studies on adult, developing, reactive and cultured astrocytes. J Exp Biol. 1981;95:35-48.
34. Janzer RC, Raff MC. Astrocytes induce blood-brain barrier properties in endothelial cells. Nature. 1987;325(6101):253-7.
35. Araya R, Kudo M, Kawano M, Ishii K, Hashikawa T, Iwasato T, et al. Bmp signaling through bmpria in astrocytes is essential for proper cerebral angiogenesis and formation of the blood-brain-barrier. Mol Cell Neurosci. 2008;38(3):417-30.
36. Alvarez J, Dodelet-Devillers A, Kebir H, Ifergan I, Fabre P, Terouz S, et al. The hedgehog pathway promotes blood-brain barrier integrity and cns immune quiescence. Science. 2011;334(6063):1727-31.
37. Mignot C, Boespflug-Tanguy O, Gelot A, Dautigny A, Pham-Dinh D, Rodriguez D. Alexander disease: Putative mechanisms of an astrocytic encephalopathy. Cell Mol Life Sci. 2004;61(3):369-85.
38. Towfighi J, Young R, Sassani J, Ramer J, Horoupian D. Alexander's disease: Further light-, and electron-microscopic observations. Acta Neuropathol. 1983;61(1):36-42.
39. Rodriguez, D. Leukodystrophies with astrocytic dysfunction. Handb Clin Neurol. 2013;113:1619-28.
40. Van Der Knaap M, Boor I, Estévez R. Megalencephalic leukoencephalopathy with subcortical cysts: Chronic white matter oedema due to a defect in brain ion and water homoeostasis. Lancet Neurol. 2012;11(11):973-85.
41. Alitalo, K. The lymphatic vasculature in disease. Nat Med. 2011;17(11):1371-80.
42. Iliff J, Wang M, Liao Y, Plogg B, Peng W, Gundersen G, et al. A paravascular pathway facilitates csf flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med. 2012;4(147).
43. Weller R, Djuanda E, Yow H-Y, Carare R. Lymphatic drainage of the brain and the pathophysiology of neurological disease. Acta Neuropathol. 2009;117(1):1-14.
44. Prinz M, Priller J, Sisodia S, Ransohoff R. Heterogeneity of cns myeloid cells and their roles in neurodegeneration. Nat Neurosci. 2011;14(10):1227-35.
45. Bechmann I, Priller J, Kovac A, Böntert M, Wehner T, Klett F, et al. Immune surveillance of mouse brain perivascular spaces by blood-borne macrophages. Eur J Neurosci. 2001;14(10):1651-8.
46. Ransohoff R, Engelhardt B. The anatomical and cellular basis of immune surveillance in the central nervous system. Nat Rev Immunol. 2012;12(9):623-35.
47. Kim W-K, Alvarez X, Fisher J, Bronfin B, Westmoreland S, Mclaurin J, et al. Cd163 identifies perivascular macrophages in normal and viral encephalitic brains and potential precursors to perivascular macrophages in blood. Am J Pathol. 2006;168(3):822-34.
48. Wynn T, Chawla A, Pollard J. Macrophage biology in development, homeostasis and disease. Nature. 2013;496(7446):445-55.
49. Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 2005;308(5726):1314-8.
50. Lebleu V, Macdonald B, Kalluri, R. Structure and function of basement membranes. Exp Biol Med (Maywood)., 2007;232(9):1121-9.
51. Engelhardt B, Ransohoff R. Capture, crawl, cross: The t cell code to breach the blood-brain barriers. Trends Immunol. 2012;33(12):579-89.
52. Gould D, Phalan F, Van Mil S, Sundberg J, Vahedi K, Massin P, et al. Role of col4a1 in small-vessel disease and hemorrhagic stroke. N Engl J Med. 2006;354(14):1489-96.
53. Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont M, et al. Col4a1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. N Engl J Med. 2007;357(26):2687-95.
54. Jeanne M, Labelle-Dumais C, Jorgensen J, Kauffman W, Mancini G, Favor J, et al. Col4a2 mutations impair col4a1 and col4a2 secretion and cause hemorrhagic stroke. Am J Human Genet. 2012;90(1):91-101.
55. Allamand V, Guicheney P. Merosin-deficient congenital muscular dystrophy, autosomal recessive (mdc1a, mim#156225, lama2 gene coding for alpha2 chain of laminin). Eur J Hum Genet. 2002;10(2):91-4.
56. Sijens P, Fock J, Meiners L, Potze J, Irwan R, Oudkerk M. Mr spectroscopy and diffusion tensor imaging of the brain in congenital muscular dystrophy with merosin deficiency: Metabolite level decreases, fractional anisotropy decreases, and apparent diffusion coefficient increases in the white matter. Brain Dev. 2007;29(5):317-21.
57. Reese TS, Karnovsky MJ. Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol. 1967;34(1):207-17.
58. Dejana E, Tournier-Lasserve E, Weinstein B. The control of vascular integrity by endothelial cell junctions: Molecular basis and pathological implications. Dev Cell. 2009;16(2):209-21.
59. Zheng P-P, Severijnen L-A, Van Der Weiden M, Willemsen R, Kros J. A crucial role of caldesmon in vascular development in vivo. Cardiovasc Res. 2009;81(2):362-9.
60. Li F Lan Y, Wang Y, Wang J, Yang G, Meng F, et al. Endothelial smad4 maintains cerebrovascular integrity by activating n-cadherin through cooperation with notch. Dev Cell. 2011;20(3):291-302.
61. Taddei A, Giampietro C, Conti A, Orsenigo F, Breviario F, Pirazzoli V, et al. Endothelial adherens junctions control tight junctions by ve-cadherin-mediated upregulation of claudin-5. Nat Cell Biol. 2008;10(8):923-34.
62. Saitou M, Furuse M, Sasaki H, Schulzke J, Fromm M, Takano H, et al. Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell. 2000;11(12):4131-42.
63. O'driscoll M, Daly S, Urquhart J, Black G, Pilz D, Brockmann K, et al. Recessive mutations in the gene encoding the tight junction protein occludin cause band-like calcification with simplified gyration and polymicrogyria. Am J Human Genet. 2010;87(3):354-64.
64. Mochida G, Ganesh V, Felie J, Gleason D, Hill R, Clapham K, et al. A homozygous mutation in the tight-junction protein jam3 causes hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts. Am J Human Genet. 2010;87(6):882-9.
65. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13-25.
66. Brockmann K. The expanding phenotype of glut1-deficiency syndrome. Brain & development. 2009;31(7):545-52.
67. Zheng P-P, Romme E, Van Der Spek P, Dirven C, Willemsen R, Kros J. Glut1/slc2a1 is crucial for the development of the blood-brain barrier in vivo. Ann Neurol. 2010;68(6):835-44.
68. Braun D, Wirth E, Schweizer U. Thyroid hormone transporters in the brain. Rev Neurosci. 2010;21(3):173-86.
69. Heuer H, Visser T. The pathophysiological consequences of thyroid hormone transporter deficiencies: Insights from mouse models. Biochim Biophys Acta. 2013;1830(7):3974-8.
70. Miller, DS. Regulation of p-glycoprotein and other abc drug transporters at the blood-brain barrier. Trends Pharmacol Sci. 2010;31(6):246-54.
71. Dean M, Annilo T. Evolution of the atp-binding cassette (abc) transporter superfamily in vertebrates. Annu Rev Genomics Hum Genet. 2005;6:123-42.
72. Hervé D, Chabriat H, Rigal M, Dalloz M-A, Kawkabani Marchini A, De Lepeleire J, et al. A novel hereditary extensive vascular leukoencephalopathy mapping to chromosome 20q13. Neurology. 2012;79(23):2283-7.
73. Fischer A, Zalvide J, Faurobert E, Albiges-Rizo C,Tournier-Lasserve E. Cerebral cavernous malformations: From ccm genes to endothelial cell homeostasis. Trends Mol Med. 2013;19(5):302-8.
74. Labauge P, Denier C, Bergametti F, Tournier-Lasserve E. Genetics of cavernous angiomas. Lancet Neurol. 2007;6(3):237-44.
75. Stanimirovic D, Friedman A. Pathophysiology of the neurovascular unit: Disease cause or consequence? J Cereb Blood Flow Metab. 2012;32(7):1207-21.
76. Zlokovic B. Neurovascular pathways to neurodegeneration in alzheimer's disease and other disorders. Nat Rev Neurosci. 2011;12(12):723-38.
77. Muldoon L, Alvarez J, Begley D, Boado R, Del Zoppo G, Doolittle N, et al. Immunologic privilege in the central nervous system and the blood-brain barrier. J Cereb Blood Flow Metab. 2013;33(1):13-21.
78. Nguyen, J. Blood-brain barrier in acute liver failure. Neurochem Int. 2012;60(7):676-83.
79. Cauli O, López-Larrubia P, Rodrigo R, Agusti A, Boix J, Nieto-Charques L, et al. Brain region-selective mechanisms contribute to the progression of cerebral alterations in acute liver failure in rats. Gastroenterology. 2011;140(2):638-45.
80. Gove C, Hughes R, Ede R, Williams R. Regional cerebral edema and chloride space in galactosamine-induced liver failure in rats. Hepatology. 1997;25(2):295-301.
81. Kato M, Hughes R, Keays R, Williams R. Electron microscopic study of brain capillaries in cerebral edema from fulminant hepatic failure. Hepatology. 1992;15(6):1060-6.
82. Traber P, Dal Canto M, Ganger D, Blei A. Electron microscopic evaluation of brain edema in rabbits with galactosamine-induced fulminant hepatic failure: Ultrastructure and integrity of the blood-brain barrier. Hepatology. 1987;7(6):1272-7.
83. Stevens C, Heran M. The many faces of posterior reversible encephalopathy syndrome. Br J Radiol. 2012;85(1020):1566-75.
84. Vacas S, Degos V, Feng X, Maze M. The neuroinflammatory response of postoperative cognitive decline. Br Med Bull. 2013.
85. Terrando N, Eriksson L, Ryu J, Yang T, Monaco C, Feldmann M, et al. Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol. 2011;70(6):986-95.
86. Tétrault S, Chever O, Sik A, Amzica F. Opening of the blood-brain barrier during isoflurane anaesthesia. Eur J Neurosci. 2008;28(7):1330-41.
87. Cibelli M, Fidalgo A, Terrando N, Ma D, Monaco C, Feldmann M, et al. Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol. 2010;68(3):360-8.
88. Petito C. Early and late mechanisms of increased vascular permeability following experimental cerebral infarction. J Neuropath Exp Neurol. 1979;38(3):222-34.
89. Sato H, Tanaka T, Kasai K, Tanaka N. An autopsy case of acute carbon monoxide poisoning after a long-term vegetative state. Am J Forensic Med Pathol. 2012;33(4):341-3.
90. Hackett P, Roach R. High-altitude illness. N Engl J Med. 2001;345(2):107-14.
91. Schoch H, Fischer S, Marti H. Hypoxia-induced vascular endothelial growth factor expression causes vascular leakage in the brain. Brain. 2002;125(Pt 11):2549-57.
92. Pichiule P, Chávez J, Xu K, Lamanna J. Vascular endothelial growth factor upregulation in transient global ischemia induced by cardiac arrest and resuscitation in rat brain. Brain Res Mol Brain Res. 1999;74(1-2):83-90.
93. Zhang W, Han Y, Lim S, Lim L. Dietary regulation of p-gp function and expression. Expert Opin Drug Metab Toxicol. 2009;5(7):789-801.
94. Prins M. Cerebral metabolic adaptation and ketone metabolism after brain injury. J Cereb Blood Flow Metab. 2008;28(1):1-16.
95. Pierre K, Parent A, Jayet P-Y, Halestrap A, Scherrer U, Pellerin L. Enhanced expression of three monocarboxylate transporter isoforms in the brain of obese mice. J Physiol. 2007;583(Pt 2):469-86.
96. Canis M, Maurer M, Kuschinsky W, Duembgen L, Duelli R. Increased densities of monocarboxylate transporter mct1 after chronic hyperglycemia in rat brain. Brain Res. 2009;1257:32-9.
97. Richard LL, David ZG, Roman D, Bradley EE, Lester RD. Diet-induced ketosis increases monocarboxylate transporter (mct1) levels in rat brain. Neurochem Int. 2001;38.
98. Andrews M, Russeth K, Drewes L, Henry P-G. Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor. Am J Physiol Regul Integr Comp Physiol. 2009;296(2):93.
99. Langlet F, Levin B, Luquet S, Mazzone M, Messina A, Dunn-Meynell A, et al. Tanycytic vegf-a boosts blood-hypothalamus barrier plasticity and access of metabolic signals to the arcuate nucleus in response to fasting. Cell Metab. 2013;17(4):607-17.