Structure and Function of the Blood-Brain Barrier (BBB).
BBB development
Blood–brain barrier
Circumventricular organs
Neurovascular unit
Vascular heterogeneity
Wnt signalling
Journal
Handbook of experimental pharmacology
ISSN: 0171-2004
Titre abrégé: Handb Exp Pharmacol
Pays: Germany
ID NLM: 7902231
Informations de publication
Date de publication:
2022
2022
Historique:
pubmed:
30
11
2020
medline:
16
6
2022
entrez:
29
11
2020
Statut:
ppublish
Résumé
The blood-brain barrier (BBB) protects the vertebrate central nervous system from harmful blood-borne, endogenous and exogenous substances to ensure proper neuronal function. The BBB describes a function that is established by endothelial cells of CNS vessels in conjunction with pericytes, astrocytes, neurons and microglia, together forming the neurovascular unit (NVU). Endothelial barrier function is crucially induced and maintained by the Wnt/β-catenin pathway and requires intact NVU for proper functionality. The BBB and the NVU are characterized by a specialized assortment of molecular specializations, providing the basis for tightening, transport and immune response functionality.The present chapter introduces state-of-the-art knowledge of BBB structure and function and highlights current research topics, aiming to understanding in more depth the cellular and molecular interactions at the NVU, determining functionality of the BBB in health and disease, and providing novel potential targets for therapeutic BBB modulation. Moreover, we highlight recent advances in understanding BBB and NVU heterogeneity within the CNS as well as their contribution to CNS physiology, such as neurovascular coupling, and pathophysiology, is discussed. Finally, we give an outlook onto new avenues of BBB research.
Identifiants
pubmed: 33249527
doi: 10.1007/164_2020_404
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3-31Informations de copyright
© 2020. Springer Nature Switzerland AG.
Références
Abbott NJ, Rönnbäck L, Hansson E (2006) Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci 7:41–53
pubmed: 16371949
doi: 10.1038/nrn1824
Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ (2010) Structure and function of the blood-brain barrier. Neurobiol Dis 37:13–25
pubmed: 19664713
doi: 10.1016/j.nbd.2009.07.030
Alfonso J, Le Magueresse C, Zuccotti A, Khodosevich K, Monyer H (2012) Diazepam binding inhibitor promotes progenitor proliferation in the postnatal SVZ by reducing GABA signaling. Cell Stem Cell 10:76–87
pubmed: 22226357
doi: 10.1016/j.stem.2011.11.011
Alvarez JI, Dodelet-Devillers A, Kebir H et al (2011) The hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence. Science 334:1727–7731
pubmed: 22144466
doi: 10.1126/science.1206936
Ances BM, Buerk DG, Greenberg JH, Detre JA (2001) Temporal dynamics of the partial pressure of brain tissue oxygen during functional forepaw stimulation in rats. Neurosci Lett 306:106–110
pubmed: 11403969
doi: 10.1016/S0304-3940(01)01868-7
Andreone BJ, Lacoste B, Gu C (2015) Neuronal and vascular interactions. Annu Rev Neurosci 38:25–46
pubmed: 25782970
pmcid: 5729758
doi: 10.1146/annurev-neuro-071714-033835
Armulik A, Genové G, Mäe M et al (2010) Pericytes regulate the blood–brain barrier. Nature 468:557–561
pubmed: 20944627
doi: 10.1038/nature09522
Augustine V, Gokce SK, Lee S, Wang B, Davidson TJ, Reimann F, Gribble F, Deisseroth K, Lois C, Oka Y (2018) Hierarchical neural architecture underlying thirst regulation. Nature 555:204–209
pubmed: 29489747
pmcid: 6086126
doi: 10.1038/nature25488
Barar J, Rafi MA, Pourseif MM, Omidi Y (2017) Blood-brain barrier transport machineries and targeted therapy of brain diseases. Tabriz Univ Med Sci 6:225–248
Behnsen G (1927) Über die Farbstoffspeicherung im Zentralnervensystem der weissen Maus in verschiedenen Alterszuständen. Cell Tissue Res 4:515–572
Belova I, Jonsson G (1982) Blood-brain barrier permeability and immobilization stress. Acta Physiol Scand 116:21–29
pubmed: 6891559
doi: 10.1111/j.1748-1716.1982.tb10594.x
Bennett L, Yang M, Enikolopov G, Iacovitti L (2009) Circumventricular organs: a novel site of neural stem cells in the adult brain. Mol Cell Neurosci 41:337–347
pubmed: 19409493
pmcid: 2697272
doi: 10.1016/j.mcn.2009.04.007
Benz F, Wichitnaowarat V, Lehmann M et al (2019) Low wnt/β-catenin signaling determines leaky vessels in the subfornical organ and affects water homeostasis in mice. elife 8:204
doi: 10.7554/eLife.43818
Ben-Zvi A, Lacoste B, Kur E, Andreone BJ, Mayshar Y, Yan H, Gu C (2014) Mfsd2a is critical for the formation and function of the blood–brain barrier. Nature:1–18
Berndt P, Winkler L, Cording J et al (2019) Tight junction proteins at the blood-brain barrier: far more than claudin-5. Cell Mol Life Sci 76:1987–2002
pubmed: 30734065
doi: 10.1007/s00018-019-03030-7
Blanchette M, Daneman R (2015) Formation and maintenance of the BBB. Mech Dev 138(Pt 1):8–16
pubmed: 26215350
doi: 10.1016/j.mod.2015.07.007
Bonney S, Siegenthaler JA (2017) Differential effects of retinoic acid concentrations in regulating blood-brain barrier properties. eNeuro 4
Brightman MW, Reese TS (1969) Junctions between intimately apposed cell membranes in the vertebrate brain. J Cell Biol 40:648–677
pubmed: 5765759
pmcid: 2107650
doi: 10.1083/jcb.40.3.648
Bundgaard M, Abbott NJ (2008) All vertebrates started out with a glial blood-brain barrier 4-500 million years ago. Glia 56:699–708
pubmed: 18338790
doi: 10.1002/glia.20642
Campos CR, Schröter C, Wang X, Miller DS (2012) ABC transporter function and regulation at the blood-spinal cord barrier. J Cereb Blood Flow Metab 32:1559–1566
pubmed: 22472606
pmcid: 3421094
doi: 10.1038/jcbfm.2012.47
Castro Dias M, Coisne C, Lazarevic I et al (2019) Claudin-3-deficient C57BL/6J mice display intact brain barriers. Sci Rep 9:203
pubmed: 30659216
pmcid: 6338742
doi: 10.1038/s41598-018-36731-3
Chang J, Mancuso MR, Maier C et al (2017) Gpr124 is essential for blood-brain barrier integrity in central nervous system disease. Nat Med 23:450–460
pubmed: 28288111
pmcid: 5559385
doi: 10.1038/nm.4309
Chen BR, Kozberg MG, Bouchard MB, Shaik MA, Hillman EMC (2014) A critical role for the vascular endothelium in functional neurovascular coupling in the brain. J Am Heart Assoc 3:e000787
pubmed: 24926076
pmcid: 4309064
doi: 10.1161/JAHA.114.000787
Cording J, Berg J, Käding N et al (2012) Tight junctions: Claudins regulate the interactions between occludin, tricellulin and marvelD3, which, inversely, modulate claudin oligomerization. J Cell Sci. https://doi.org/10.1242/jcs.114306
Daneman R, Agalliu D, Zhou L, Kuhnert F, Kuo CJ, Barres BA (2009) Wnt/beta-catenin signaling is required for CNS, but not non-CNS, angiogenesis. Proc Natl Acad Sci 106:641–646
pubmed: 19129494
pmcid: 2626756
doi: 10.1073/pnas.0805165106
Daneman R, Zhou L, Kebede AA, Barres BA (2010a) Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 468:562–566
pubmed: 20944625
pmcid: 3241506
doi: 10.1038/nature09513
Daneman R, Zhou L, Agalliu D, Cahoy JD, Kaushal A, Barres BA (2010b) The mouse blood-brain barrier transcriptome: a new resource for understanding the development and function of brain endothelial cells. PLoS One 5:e13741
pubmed: 21060791
pmcid: 2966423
doi: 10.1371/journal.pone.0013741
Daneman R, Daneman R, Prat A, Prat A (2015) The blood-brain barrier. Cold Spring Harb Perspect Biol 7:a020412
pubmed: 25561720
pmcid: 4292164
doi: 10.1101/cshperspect.a020412
Daniel PM, Lam DK, Pratt OE (1985) Comparison of the vascular permeability of the brain and the spinal cord to mannitol and inulin in rats. J Neurochem 45:647–649
pubmed: 3925086
doi: 10.1111/j.1471-4159.1985.tb04038.x
Darlington TK, Wager-Smith K, Ceriani MF, Staknis D, Gekakis N, Steeves TD, Weitz CJ, Takahashi JS, Kay SA (1998) Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim. Science 280:1599–1603
pubmed: 9616122
doi: 10.1126/science.280.5369.1599
Dauchy S, Dutheil F, Weaver RJ, Chassoux F, Daumas-Duport C, Couraud P-O, Scherrmann J-M, de Waziers I, Declèves X (2008) ABC transporters, cytochromes P450 and their main transcription factors: expression at the human blood-brain barrier. J Neurochem 107:1518–1528
pubmed: 19094056
doi: 10.1111/j.1471-4159.2008.05720.x
Davis DA, Milhorat TH (1975) The blood-brain barrier of the rat choroid plexus. Anat Rec 181:779–789
pubmed: 164140
doi: 10.1002/ar.1091810409
Dejana E, Orsenigo F (2013) Endothelial adherens junctions at a glance. J Cell Sci 126:2545–2549
pubmed: 23781019
Dennis MS, Watts RJ (2012) Transferrin antibodies into the brain. Neuropsychopharmacology 37:302–303
pubmed: 22157868
doi: 10.1038/npp.2011.196
Doetsch F (2003) A niche for adult neural stem cells. Curr Opin Genet Dev 13:543–550
pubmed: 14550422
doi: 10.1016/j.gde.2003.08.012
Doetsch F, Caillé I, Lim DA, García-Verdugo JM, Alvarez-Buylla A (1999) Subventricular zone astrocytes are neural stem cells in the adult mammalian brain. Cell 97:703–716
pubmed: 10380923
doi: 10.1016/S0092-8674(00)80783-7
Duelli R, Enerson BE, Gerhart DZ, Drewes LR (2000) Expression of large amino acid transporter LAT1 in rat brain endothelium. J Cereb Blood Flow Metab 20:1557–1562
pubmed: 11083230
doi: 10.1097/00004647-200011000-00005
Ek CJ, Wong A, Liddelow SA, Johansson PA, Dziegielewska KM, Saunders NR (2010) Efflux mechanisms at the developing brain barriers: ABC-transporters in the fetal and postnatal rat. Toxicol Lett 197:51–59
pubmed: 20466047
doi: 10.1016/j.toxlet.2010.04.025
Emery P, So WV, Kaneko M, Hall JC, Rosbash M (1998) CRY, a drosophila clock and light-regulated cryptochrome, is a major contributor to circadian rhythm resetting and photosensitivity. Cell 95:669–679
pubmed: 9845369
doi: 10.1016/S0092-8674(00)81637-2
Engelhardt B, Sorokin L (2009) The blood-brain and the blood-cerebrospinal fluid barriers: function and dysfunction. Semin Immunopathol 31:497–511
pubmed: 19779720
doi: 10.1007/s00281-009-0177-0
Eubelen M, Bostaille N, Cabochette P et al (2018) A molecular mechanism for Wnt ligand-specific signaling. Science 361:eaat1178
pubmed: 30026314
doi: 10.1126/science.aat1178
Fernando RN, Eleuteri B, Abdelhady S, Nussenzweig A, Andäng M, Ernfors P (2011) Cell cycle restriction by histone H2AX limits proliferation of adult neural stem cells. Proc Natl Acad Sci 108:5837–5842
pubmed: 21436033
pmcid: 3078396
doi: 10.1073/pnas.1014993108
Flemming KD, Graff-Radford J, Aakre J et al (2017) Population-based prevalence of cerebral cavernous malformations in older adults: Mayo clinic study of aging. JAMA Neurol 74:801–805
pubmed: 28492932
pmcid: 5647645
doi: 10.1001/jamaneurol.2017.0439
Fujioka T, Kaneko N, Sawamoto K (2019) Blood vessels as a scaffold for neuronal migration. Neurochem Int 126:69–73
pubmed: 30851365
doi: 10.1016/j.neuint.2019.03.001
Fultz NE, Bonmassar G, Setsompop K, Stickgold RA, Rosen BR, Polimeni JR, Lewis LD (2019) Coupled electrophysiological, hemodynamic, and cerebrospinal fluid oscillations in human sleep. Science 366:628–631
pubmed: 31672896
pmcid: 7309589
doi: 10.1126/science.aax5440
Furube E, Morita M, Miyata S (2015) Characterization of neural stem cells and their progeny in the sensory circumventricular organs of adult mouse. Cell Tissue Res 362:347–365
pubmed: 25994374
doi: 10.1007/s00441-015-2201-0
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
pubmed: 10562289
pmcid: 2156154
doi: 10.1083/jcb.147.4.891
García-Lecea M, Gasanov E, Jedrychowska J, Kondrychyn I, Teh C, You M-S, Korzh V (2017) Development of circumventricular organs in the mirror of zebrafish enhancer-trap transgenics. Front Neuroanat 11:114
pubmed: 29375325
pmcid: 5770639
doi: 10.3389/fnana.2017.00114
Garrido-Urbani S, Bradfield PF, Imhof BA (2014) Tight junction dynamics: the role of junctional adhesion molecules (JAMs). Cell Tissue Res 355:701–715
pubmed: 24595739
doi: 10.1007/s00441-014-1820-1
Ge S, Pachter JS (2006) Isolation and culture of microvascular endothelial cells from murine spinal cord. J Neuroimmunol 177:209–214
pubmed: 16806499
doi: 10.1016/j.jneuroim.2006.05.012
Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP, Takahashi JS, Weitz CJ (1998) Role of the CLOCK protein in the mammalian circadian mechanism. Science 280:1564–1569
pubmed: 9616112
doi: 10.1126/science.280.5369.1564
Gizowski C, Zaelzer C, Bourque CW (2016) Clock-driven vasopressin neurotransmission mediates anticipatory thirst prior to sleep. Nature 537:685–688
pubmed: 27680940
doi: 10.1038/nature19756
Gizowski C, Zaelzer C, Bourque CW (2018) Activation of organum vasculosum neurons and water intake in mice by vasopressin neurons in the suprachiasmatic nucleus. J Neuroendocrinol 30:e12577
doi: 10.1111/jne.12577
Gleerup HS, Hasselbalch SG, Simonsen AH (2019) Biomarkers for Alzheimer’s disease in saliva: a systematic review. Dis Markers 2019:1–11. https://doi.org/10.1155/2019/4761054
doi: 10.1155/2019/4761054
Goldberg JS, Hirschi KK (2009) Diverse roles of the vasculature within the neural stem cell niche. Regen Med 4:879–897
pubmed: 19903006
doi: 10.2217/rme.09.61
Gordon GRJ, Choi HB, Rungta RL, Ellis-Davies GCR, Macvicar BA (2008) Brain metabolism dictates the polarity of astrocyte control over arterioles. Nature 456:745–749
pubmed: 18971930
pmcid: 4097022
doi: 10.1038/nature07525
Gordon GRJ, Howarth C, Macvicar BA (2011) Bidirectional control of arteriole diameter by astrocytes. Exp Physiol 96:393–399
pubmed: 21257665
doi: 10.1113/expphysiol.2010.053132
Grobe JL, Buehrer BA, Hilzendeger AM, Liu X, Davis DR, Xu D, Sigmund CD (2011) Angiotensinergic signaling in the brain mediates metabolic effects of deoxycorticosterone (DOCA)-salt in C57 mice. Hypertension 57:600–607
pubmed: 21263123
doi: 10.1161/HYPERTENSIONAHA.110.165829
Guadagno E, Moukhles H (2004) Laminin-induced aggregation of the inwardly rectifying potassium channel, Kir4.1, and the water-permeable channel, AQP4, via a dystroglycan-containing complex in astrocytes. Glia 47:138–149
pubmed: 15185393
doi: 10.1002/glia.20039
Guo L, Zhang H, Hou Y, Wei T, Liu J (2016) Plasmalemma vesicle-associated protein: a crucial component of vascular homeostasis. Exp Ther Med 12:1639–1644
pubmed: 27602081
pmcid: 4998186
doi: 10.3892/etm.2016.3557
Gurnik S, Devraj K, Macas J et al (2016) Angiopoietin-2-induced blood-brain barrier compromise and increased stroke size are rescued by VE-PTP-dependent restoration of Tie2 signaling. Acta Neuropathol 131:753–773
pubmed: 26932603
pmcid: 4835530
doi: 10.1007/s00401-016-1551-3
Guyenet PG (2019) Sodium is detected by the OVLT to regulate sympathetic tone. Neuron 101:3–5
pubmed: 30605656
pmcid: 6738342
doi: 10.1016/j.neuron.2018.12.015
Hagan N, Ben-Zvi A (2015) The molecular, cellular, and morphological components of blood-brain barrier development during embryogenesis. Semin Cell Dev Biol 38:7–15
pubmed: 25550218
doi: 10.1016/j.semcdb.2014.12.006
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 202:325–332
pubmed: 7626790
doi: 10.1002/aja.1002020402
Hallmann R, Zhang X, di Russo J, Li L, Song J, Hannocks M-J, Sorokin L (2015) The regulation of immune cell trafficking by the extracellular matrix. Curr Opin Cell Biol 36:54–61
pubmed: 26189064
doi: 10.1016/j.ceb.2015.06.006
Hein TW, Xu W, Kuo L (2006) Dilation of retinal arterioles in response to lactate: role of nitric oxide, guanylyl cyclase, and ATP-sensitive potassium channels. Invest Ophthalmol Vis Sci 47:693–699
pubmed: 16431969
doi: 10.1167/iovs.05-1224
Hogan-Cann AD, Lu P, Anderson CM (2019) Endothelial NMDA receptors mediate activity-dependent brain hemodynamic responses in mice. Proc Natl Acad Sci 116:10229–10231
pubmed: 31061120
pmcid: 6535036
doi: 10.1073/pnas.1902647116
Hourai A, Miyata S (2013) Neurogenesis in the circumventricular organs of adult mouse brains. J Neurosci Res 91:757–770
pubmed: 23526379
doi: 10.1002/jnr.23206
Iadecola C (2017) The neurovascular unit coming of age: a journey through neurovascular coupling in health and disease. Neuron 96:17–42
pubmed: 28957666
pmcid: 5657612
doi: 10.1016/j.neuron.2017.07.030
Ikenouchi J, Furuse M, Furuse K, Sasaki H, Tsukita S, Tsukita S (2005) Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J Cell Biol 171:939–945
pubmed: 16365161
pmcid: 2171318
doi: 10.1083/jcb.200510043
Junge HJ, Yang S, Burton JB, Paes K, Shu X, French DM, Costa M, Rice DS, Ye W (2009) TSPAN12 regulates retinal vascular development by promoting Norrin- but not Wnt-induced FZD4/beta-catenin signaling. Cell 139:299–311
pubmed: 19837033
doi: 10.1016/j.cell.2009.07.048
Kasischke KA, Vishwasrao HD, Fisher PJ, Zipfel WR, Webb WW (2004) Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 305:99–103
pubmed: 15232110
doi: 10.1126/science.1096485
Kiecker C (2017) The origins of the circumventricular organs. J Anat 53:1–14
Kniesel U, Reichenbach A, Risau W, Wolburg H (1994) Quantification of tight junction complexity by means of fractal analysis. Tissue Cell 26:901–912
pubmed: 7886676
doi: 10.1016/0040-8166(94)90039-6
Kofuji P, Ceelen P, Zahs KR, Surbeck LW, Lester HA, Newman EA (2000) Genetic inactivation of an inwardly rectifying potassium channel (Kir4.1 subunit) in mice: phenotypic impact in retina. J Neurosci 20:5733–5740
pubmed: 10908613
pmcid: 2410027
doi: 10.1523/JNEUROSCI.20-15-05733.2000
Kovács R, Heinemann U, Steinhäuser C (2012) Mechanisms underlying blood-brain barrier dysfunction in brain pathology and epileptogenesis: role of astroglia. Epilepsia 53(Suppl 6):53–59
pubmed: 23134496
doi: 10.1111/j.1528-1167.2012.03703.x
Kratzer I, Vasiljevic A, Rey C, Fèvre Montange M, Saunders N, Strazielle N, Ghersi-Egea J-F (2012) Complexity and developmental changes in the expression pattern of claudins at the blood-CSF barrier. Histochem Cell Biol 138:861–879
pubmed: 22886143
pmcid: 3483103
doi: 10.1007/s00418-012-1001-9
Lacoste B, Comin CH, Ben-Zvi A, Kaeser PS, Xu X, Costa LDF, Gu C (2014) Sensory-related neural activity regulates the structure of vascular networks in the cerebral cortex. Neuron 83:1117–1130
pubmed: 25155955
pmcid: 4166422
doi: 10.1016/j.neuron.2014.07.034
Lampugnani MG, Malinverno M, Dejana E, Rudini N (2017) Endothelial cell disease: emerging knowledge from cerebral cavernous malformations. Curr Opin Hematol 24:256–264
pubmed: 28212190
doi: 10.1097/MOH.0000000000000338
Lange A, Gebremedhin D, Narayanan J, Harder D (1997) 20-hydroxyeicosatetraenoic acid-induced vasoconstriction and inhibition of potassium current in cerebral vascular smooth muscle is dependent on activation of protein kinase C. J Biol Chem 272:27345–27352
pubmed: 9341185
doi: 10.1074/jbc.272.43.27345
Langlet F, Mullier A, Bouret SG, Prevot V, Dehouck B (2013) Tanycyte-like cells form a blood-cerebrospinal fluid barrier in the circumventricular organs of the mouse brain. J Comp Neurol 521:3389–3405
pubmed: 23649873
pmcid: 3973970
doi: 10.1002/cne.23355
Lavoie JL, Cassell MD, Gross KW, Sigmund CD (2004) Adjacent expression of renin and angiotensinogen in the rostral ventrolateral medulla using a dual-reporter transgenic model. Hypertension 43:1116–1119
pubmed: 15037561
doi: 10.1161/01.HYP.0000125143.73301.94
Lee S-W, Kim WJ, Choi YK, Song HS, Son MJ, Gelman IH, Kim Y-J, Kim K-W (2003) SSeCKS regulates angiogenesis and tight junction formation in blood-brain barrier. Nat Med 9:900–906
pubmed: 12808449
doi: 10.1038/nm889
Leib DE, Zimmerman CA, Knight ZA (2016) Thirst. Curr Biol 26:R1260–R1265
pubmed: 27997832
pmcid: 5957508
doi: 10.1016/j.cub.2016.11.019
Liddelow SA (2011) Fluids and barriers of the CNS: a historical viewpoint. Fluids Barriers CNS 8:2
pubmed: 21349150
pmcid: 3039834
doi: 10.1186/2045-8118-8-2
Liddelow SA, Dziegielewska KM, Ek CJ, Johansson PA, Potter AM, Saunders NR (2009) Cellular transfer of macromolecules across the developing choroid plexus of Monodelphis domestica. Eur J Neurosci 29:253–266
pubmed: 19200232
doi: 10.1111/j.1460-9568.2008.06571.x
Liebner S, Kniesel U, Kalbacher H, Wolburg H (2000) Correlation of tight junction morphology with the expression of tight junction proteins in blood-brain barrier endothelial cells. Eur J Cell Biol 79:707–717
pubmed: 11089919
doi: 10.1078/0171-9335-00101
Liebner S, Corada M, Bangsow T et al (2008) Wnt/beta-catenin signaling controls development of the blood-brain barrier. J Cell Biol 183:409–417
pubmed: 18955553
pmcid: 2575783
doi: 10.1083/jcb.200806024
Lim DA, Tramontin AD, Trevejo JM, Herrera DG, García-Verdugo JM, Alvarez-Buylla A (2000) Noggin antagonizes BMP signaling to create a niche for adult neurogenesis. Neuron 28:713–726
pubmed: 11163261
doi: 10.1016/S0896-6273(00)00148-3
Lin R, Lang M, Heinsinger N, Stricsek G, Zhang J, Iozzo R, Rosenwasser R, Iacovitti L (2018) Stepwise impairment of neural stem cell proliferation and neurogenesis concomitant with disruption of blood-brain barrier in recurrent ischemic stroke. Neurobiol Dis 115:49–58
pubmed: 29605425
doi: 10.1016/j.nbd.2018.03.013
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 17:1835–1840
pubmed: 12897053
pmcid: 196228
doi: 10.1101/gad.266803
Lippmann ES, Al-Ahmad A, Azarin SM, Palecek SP, Shusta EV (2014) A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources. Sci Rep. https://doi.org/10.1038/srep04160
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
pubmed: 10841351
doi: 10.1097/00001756-200005150-00015
Liu Y, Ford BD, Mann MA, Fischbach GD (2005) Neuregulin-1 increases the proliferation of neuronal progenitors from embryonic neural stem cells. Dev Biol 283:437–445
pubmed: 15949792
doi: 10.1016/j.ydbio.2005.04.038
Longden TA, Dabertrand F, Koide M, Gonzales AL, Tykocki NR, Brayden JE, Hill-Eubanks D, Nelson MT (2017) Capillary K+-sensing initiates retrograde hyperpolarization to increase local cerebral blood flow. Nat Neurosci 20:717–726
pubmed: 28319610
pmcid: 5404963
doi: 10.1038/nn.4533
Lun MP, Monuki ES, Lehtinen MK (2015) Development and functions of the choroid plexus–cerebrospinal fluid system. Nat Rev Neurosci 16:445–457
pubmed: 26174708
pmcid: 4629451
doi: 10.1038/nrn3921
Macvicar BA, Newman EA (2015) Astrocyte regulation of blood flow in the brain. Cold Spring Harb Perspect Biol 7:a020388
pubmed: 25818565
pmcid: 4448617
doi: 10.1101/cshperspect.a020388
Mahringer A, Fricker G (2016) ABC transporters at the blood-brain barrier. Expert Opin Drug Metab Toxicol 12:499–508
pubmed: 26998936
doi: 10.1517/17425255.2016.1168804
Malonek D, Grinvald A (1996) Interactions between electrical activity and cortical microcirculation revealed by imaging spectroscopy: implications for functional brain mapping. Science 272:551–554
pubmed: 8614805
doi: 10.1126/science.272.5261.551
Malonek D, Dirnagl U, Lindauer U, Yamada K, Kanno I, Grinvald A (1997) Vascular imprints of neuronal activity: relationships between the dynamics of cortical blood flow, oxygenation, and volume changes following sensory stimulation. Proc Natl Acad Sci U S A 94:14826–14831
pubmed: 9405698
pmcid: 25122
doi: 10.1073/pnas.94.26.14826
Mark MH, Farmer PM (1984) The human subfornical organ: an anatomic and ultrastructural study. Ann Clin Lab Sci 14:427–442
pubmed: 6391361
Masuda S, Oda Y, Sasaki H, Ikenouchi J, Higashi T, Akashi M, Nishi E, Furuse M (2011) LSR defines cell corners for tricellular tight junction formation in epithelial cells. J Cell Sci 124:548–555
pubmed: 21245199
doi: 10.1242/jcs.072058
Maxwell DS, Pease DC (1956) The electron microscopy of the choroid plexus. J Biophys Biochem Cytol 2:467–474
pubmed: 13357511
pmcid: 2229709
doi: 10.1083/jcb.2.4.467
Mazzoni J, Smith JR, Shahriar S, Cutforth T, Ceja B, Agalliu D (2017) The Wnt inhibitor Apcdd1 coordinates vascular remodeling and barrier maturation of retinal blood vessels. Neuron 96:1055–1069.e6
pubmed: 29154126
pmcid: 5728434
doi: 10.1016/j.neuron.2017.10.025
Metea MR, Newman EA (2006) Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling. J Neurosci 26:2862–2870
pubmed: 16540563
pmcid: 2270788
doi: 10.1523/JNEUROSCI.4048-05.2006
Miller DS (2015) Regulation of ABC transporters at the blood-brain barrier. Clin Pharmacol Ther 97:395–403
pubmed: 25670036
doi: 10.1002/cpt.64
Miller RL, Wang MH, Gray PA, Salkoff LB, Loewy AD (2013) ENaC-expressing neurons in the sensory circumventricular organs become c-Fos activated following systemic sodium changes. AJP Regul Integr Comp Physiol 305:R1141–R1152
doi: 10.1152/ajpregu.00242.2013
Mizee MR, Wooldrik D, Lakeman KAM et al (2013) Retinoic acid induces blood-brain barrier development. J Neurosci 33:1660–1671
pubmed: 23345238
pmcid: 6618717
doi: 10.1523/JNEUROSCI.1338-12.2013
Morita S, Miyata S (2012) Different vascular permeability between the sensory and secretory circumventricular organs of adult mouse brain. Cell Tissue Res 349:589–603
pubmed: 22584508
doi: 10.1007/s00441-012-1421-9
Morita K, Sasaki H, Furuse M, Tsukita S (1999) Endothelial claudin: claudin-5/TMVCF constitutes tight junction strands in endothelial cells. J Cell Biol 147:185–194
pubmed: 10508865
pmcid: 2164984
doi: 10.1083/jcb.147.1.185
Morita S, Hourai A, Miyata S (2014) Changes in pericytic expression of NG2 and PDGFRB and vascular permeability in the sensory circumventricular organs of adult mouse by osmotic stimulation. Cell Biochem Funct 32:51–61
pubmed: 23629811
doi: 10.1002/cbf.2971
Morita S, Furube E, Mannari T, Okuda H, Tatsumi K, Wanaka A, Miyata S (2015) Vascular endothelial growth factor-dependent angiogenesis and dynamic vascular plasticity in the sensory circumventricular organs of adult mouse brain. Cell Tissue Res 359:865–884
pubmed: 25573819
doi: 10.1007/s00441-014-2080-9
Morita S, Furube E, Mannari T, Okuda H, Tatsumi K, Wanaka A, Miyata S (2016) Heterogeneous vascular permeability and alternative diffusion barrier in sensory circumventricular organs of adult mouse brain. Cell Tissue Res 363:497–511
pubmed: 26048259
doi: 10.1007/s00441-015-2207-7
Moura DAP, Lemos RR, Oliveira JRM (2017) New data from Pdfgb ret/ret mutant mice might Lead to a paradoxical association between brain calcification, Pericytes recruitment and BBB integrity. J Mol Neurosci 63:419–421
pubmed: 29098547
doi: 10.1007/s12031-017-0992-z
Mullier A, Bouret SG, Prevot V, Dehouck B (2010) Differential distribution of tight junction proteins suggests a role for tanycytes in blood-hypothalamus barrier regulation in the adult mouse brain. J Comp Neurol 518:943–962
pubmed: 20127760
pmcid: 2892518
doi: 10.1002/cne.22273
Neal EH, Marinelli NA, Shi Y et al (2019) A simplified, fully defined differentiation scheme for producing blood-brain barrier endothelial cells from human iPSCs. Stem Cell Rep 12:1380–1388
doi: 10.1016/j.stemcr.2019.05.008
Nguyen LN, Ma D, Shui G, Wong P, Cazenave-Gassiot A, Zhang X, Wenk MR, Goh ELK, Silver DL (2014) Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. Nature 509:503–506
pubmed: 24828044
doi: 10.1038/nature13241
Niewoehner J, Bohrmann B, Collin L et al (2014) Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle. Neuron 81:49–60
pubmed: 24411731
doi: 10.1016/j.neuron.2013.10.061
Nishijima T, Piriz J, Duflot S et al (2010) Neuronal activity drives localized blood-brain-barrier transport of serum insulin-like growth factor-I into the CNS. Neuron 67:834–846
pubmed: 20826314
doi: 10.1016/j.neuron.2010.08.007
Nitta T, Hata M, Gotoh S, Seo Y, Sasaki H, Hashimoto N, Furuse M, Tsukita S (2003) Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. J Cell Biol 161:653–660
pubmed: 12743111
pmcid: 2172943
doi: 10.1083/jcb.200302070
Noell S, Fallier-Becker P, Beyer C, Kröger 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
pubmed: 17927773
doi: 10.1111/j.1460-9568.2007.05850.x
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
pubmed: 19449033
doi: 10.1007/s00441-009-0812-z
Nomura K, Hiyama TY, Sakuta H et al (2019) [Na+] increases in body fluids sensed by central Nax induce sympathetically mediated blood pressure elevations via H+-dependent activation of ASIC1a. Neuron 101:60–75.e6
pubmed: 30503172
doi: 10.1016/j.neuron.2018.11.017
Noumbissi ME, Galasso B, Stins MF (2018) Brain vascular heterogeneity: implications for disease pathogenesis and design of in vitro blood-brain barrier models. Fluids Barriers CNS 15:12–12
pubmed: 29688865
pmcid: 5911972
doi: 10.1186/s12987-018-0097-2
Obernier K, Alvarez-Buylla A (2019) Neural stem cells: origin, heterogeneity and regulation in the adult mammalian brain. Development 146:dev156059
pubmed: 30777863
pmcid: 6398449
doi: 10.1242/dev.156059
Oka Y, Ye M, Zuker CS (2015) Thirst driving and suppressing signals encoded by distinct neural populations in the brain. Nature:1–12
Olsson B, Blennow K, Zetterberg H (2016) The clinical value of fluid biomarkers for dementia diagnosis – Authors' reply. Lancet Neurol 15:1204–1205
pubmed: 27751544
doi: 10.1016/S1474-4422(16)30247-2
Ottone C, Krusche B, Whitby A, Clements M, Quadrato G, Pitulescu ME, Adams RH, Parrinello S (2014) Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells. Nat Cell Biol 16:1045–1056
pubmed: 25283993
pmcid: 4298702
doi: 10.1038/ncb3045
Palmer TD, Willhoite AR, Gage FH (2000) Vascular niche for adult hippocampal neurogenesis. J Comp Neurol 425:479–494
pubmed: 10975875
doi: 10.1002/1096-9861(20001002)425:4<479::AID-CNE2>3.0.CO;2-3
Pan W, Banks WA, Kastin AJ (1997) Permeability of the blood-brain and blood-spinal cord barriers to interferons. J Neuroimmunol 76:105–111
pubmed: 9184639
doi: 10.1016/S0165-5728(97)00034-9
Parri HR, Crunelli V (2002) Astrocytes, spontaneity, and the developing thalamus. J Physiol Paris 96:221–230
pubmed: 12445899
doi: 10.1016/S0928-4257(02)00009-8
Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A 91:10625–10629
pubmed: 7938003
pmcid: 45074
doi: 10.1073/pnas.91.22.10625
Pelligrino DA, Vetri F, Xu H-L (2011) Purinergic mechanisms in gliovascular coupling. Semin Cell Dev Biol 22:229–236
pubmed: 21329762
pmcid: 3070818
doi: 10.1016/j.semcdb.2011.02.010
Phoenix TN, Patmore DM, Boop S et al (2016) Medulloblastoma genotype dictates blood brain barrier phenotype. Cancer Cell 29:508–522
pubmed: 27050100
pmcid: 4829447
doi: 10.1016/j.ccell.2016.03.002
Planques A, Oliveira Moreira V, Dubreuil C, Prochiantz A, Di Nardo AA (2019) OTX2 signals from the choroid plexus to regulate adult neurogenesis. eNeuro 6
Pócsai K, Kálmán M (2015) Glial and perivascular structures in the Subfornical organ. J Histochem Cytochem 63:367–383
pubmed: 25673286
pmcid: 4409944
doi: 10.1369/0022155415575027
Price MT, Olney JW, Lowry OH, Buchsbaum S (1981) Uptake of exogenous glutamate and aspartate by circumventricular organs but not other regions of brain. J Neurochem 36:1774–1780
pubmed: 6113269
doi: 10.1111/j.1471-4159.1981.tb00430.x
Price MT, Pusateri ME, Crow SE, Buchsbaum S, Olney JW, Lowry OH (1984) Uptake of exogenous aspartate into circumventricular organs but not other regions of adult mouse brain. J Neurochem 42:740–744
pubmed: 6693901
doi: 10.1111/j.1471-4159.1984.tb02745.x
Rafii S, Butler JM, Ding B-S (2016) Angiocrine functions of organ-specific endothelial cells. Nature 529:316–325
pubmed: 26791722
pmcid: 4878406
doi: 10.1038/nature17040
Raichle ME, Mintun MA (2006) Brain work and brain imaging. Annu Rev Neurosci 29:449–476
pubmed: 16776593
doi: 10.1146/annurev.neuro.29.051605.112819
Rascher G, Fischmann A, Kröger S, Duffner F, Grote E-H, Wolburg H (2002) Extracellular matrix and the blood-brain barrier in glioblastoma multiforme: spatial segregation of tenascin and agrin. Acta Neuropathol 104:85–91
pubmed: 12070669
doi: 10.1007/s00401-002-0524-x
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
pubmed: 9751776
pmcid: 21751
doi: 10.1073/pnas.95.20.11981
Reese TS, Karnovsky MJ (1967) Fine structural localization of a blood-brain barrier to exogenous peroxidase. J Cell Biol 34:207–217
pubmed: 6033532
pmcid: 2107213
doi: 10.1083/jcb.34.1.207
Reis M, Czupalla CJ, Ziegler N et al (2012) Endothelial Wnt/β-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-B expression. J Exp Med 209:1611–1627
pubmed: 22908324
pmcid: 3428944
doi: 10.1084/jem.20111580
Reiss Y, Scholz A, Plate KH (2015) The angiopoietin—tie system: common signaling pathways for angiogenesis, cancer, and inflammation. In: Endothelial signaling in development and disease. Springer, New York, pp 313–328
doi: 10.1007/978-1-4939-2907-8_13
Ridder K, Sevko A, Heide J et al (2015) Extracellular vesicle-mediated transfer of functional RNA in the tumor microenvironment. Onco Targets Ther 4:e1008371
Sakka L, Coll G, Chazal J (2011) Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol Head Neck Dis 128:309–316
pubmed: 22100360
doi: 10.1016/j.anorl.2011.03.002
Sakuta H, Lin C-H, Yamada M, Kita Y, Tokuoka SM, Shimizu T, Noda M (2019) Nax-positive glial cells in the organum vasculosum laminae terminalis produce epoxyeicosatrienoic acids to induce water intake in response to increases in [Na+] in body fluids. Neurosci Res. https://doi.org/10.1016/j.neures.2019.05.006
Sanin V, Heeß C, Kretzschmar HA, Schuller U (2013) Recruitment of neural precursor cells from circumventricular organs of patients with cerebral ischaemia. Neuropathol Appl Neurobiol 39:510–518
pubmed: 22985410
doi: 10.1111/j.1365-2990.2012.01301.x
Saunders NR, Dziegielewska KM, Møllgård K, Habgood MD (2018) Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain. J Physiol. https://doi.org/10.1113/JP275376
Segarra M, Aburto MR, Cop F et al (2018) Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system. Science 361:eaao2861–eaao2817
pubmed: 30139844
doi: 10.1126/science.aao2861
Shen Q, Wang Y, Kokovay E, Lin G, Chuang S-M, Goderie SK, Roysam B, Temple S (2008) Adult SVZ stem cells lie in a vascular niche: a quantitative analysis of niche cell-cell interactions. Cell Stem Cell 3:289–300
pubmed: 18786416
pmcid: 2747473
doi: 10.1016/j.stem.2008.07.026
Sisó S, Jeffrey M, González L (2010) Sensory circumventricular organs in health and disease. Acta Neuropathol 120:689–705
pubmed: 20830478
doi: 10.1007/s00401-010-0743-5
Skultétyová I, Tokarev D, Jezová D (1998) Stress-induced increase in blood-brain barrier permeability in control and monosodium glutamate-treated rats. Brain Res Bull 45:175–178
pubmed: 9443836
doi: 10.1016/S0361-9230(97)00335-3
Sohet F, Lin C, Munji RN et al (2015) LSR/angulin-1 is a tricellular tight junction protein involved in blood-brain barrier formation. J Cell Biol 208:703–711
pubmed: 25753034
pmcid: 4362448
doi: 10.1083/jcb.201410131
Stenman JM, Rajagopal J, Carroll TJ, Ishibashi M, McMahon J, McMahon AP (2008) Canonical Wnt signaling regulates organ-specific assembly and differentiation of CNS vasculature. Science 322:1247–1250
pubmed: 19023080
doi: 10.1126/science.1164594
Stewart PA, Wiley MJ (1981) Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: a study using quail--chick transplantation chimeras. Dev Biol 84:183–192
pubmed: 7250491
doi: 10.1016/0012-1606(81)90382-1
Strazielle N, Ghersi-Egea JF (2013) Physiology of blood-brain interfaces in relation to brain disposition of small compounds and macromolecules. Mol Pharm 10:1473–1491
pubmed: 23298398
doi: 10.1021/mp300518e
Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV (2019) Blood-brain barrier: from physiology to disease and back. Physiol Rev 99:21–78
pubmed: 30280653
doi: 10.1152/physrev.00050.2017
Tavazoie M, van der Veken L, Silva-Vargas V, Louissaint M, Colonna L, Zaidi B, Garcia-Verdugo JM, Doetsch F (2008) A specialized vascular niche for adult neural stem cells. Cell Stem Cell 3:279–288
pubmed: 18786415
pmcid: 6864413
doi: 10.1016/j.stem.2008.07.025
Thresher RJ, Vitaterna MH, Miyamoto Y et al (1998) Role of mouse cryptochrome blue-light photoreceptor in circadian photoresponses. Science 282:1490–1494
pubmed: 9822380
doi: 10.1126/science.282.5393.1490
Thurgur H, Pinteaux E (2019) Microglia in the neurovascular unit: blood-brain barrier-microglia interactions after central nervous system disorders. Neuroscience 405:55–67
pubmed: 31007172
doi: 10.1016/j.neuroscience.2018.06.046
Tietz S, Engelhardt B (2015) Brain barriers: crosstalk between complex tight junctions and adherens junctions. J Cell Biol 209:493–506
pubmed: 26008742
pmcid: 4442813
doi: 10.1083/jcb.201412147
Tornavaca O, Chia M, Dufton N, Almagro LO, Conway DE, Randi AM, Schwartz MA, Matter K, Balda MS (2015) ZO-1 controls endothelial adherens junctions, cell–cell tension, angiogenesis, and barrier formation. J Cell Biol 208:821–838
pubmed: 25753039
pmcid: 4362456
doi: 10.1083/jcb.201404140
Ulrich F, Carretero-Ortega J, Menéndez J et al (2016) Reck enables cerebrovascular development by promoting canonical Wnt signaling. Development 143:147–159
pubmed: 26657775
pmcid: 4725199
doi: 10.1242/dev.136507
Vallon M, Yuki K, Nguyen TD et al (2018) A RECK-WNT7 receptor-ligand interaction enables isoform-specific regulation of Wnt bioavailability. Cell Rep 25:339–349.e9
pubmed: 30304675
pmcid: 6338448
doi: 10.1016/j.celrep.2018.09.045
van Deurs B (1979) Cell junctions in the endothelia and connective tissue of the rat choroid plexus. Anat Rec 195:73–94
pubmed: 496029
doi: 10.1002/ar.1091950107
van Itallie CM, Anderson JM (2014) Architecture of tight junctions and principles of molecular composition. Semin Cell Dev Biol 36:157–165
pubmed: 25171873
doi: 10.1016/j.semcdb.2014.08.011
Vanhollebeke B, Stone OA, Bostaille N et al (2015) Tip cell-specific requirement for an atypical Gpr124- and Reck-dependent Wnt/β-catenin pathway during brain angiogenesis. elife 4:e06489
pmcid: 4456509
doi: 10.7554/eLife.06489
Vanlandewijck M, He L, Mäe MA et al (2018) A molecular atlas of cell types and zonation in the brain vasculature. Nature. https://doi.org/10.1038/nature25739
Vanzetta I, Grinvald A (1999) Increased cortical oxidative metabolism due to sensory stimulation: implications for functional brain imaging. Science 286:1555–1558
pubmed: 10567261
doi: 10.1126/science.286.5444.1555
Villaseñor R, Kuennecke B, Ozmen L, Ammann M, Kugler C, Grüninger F, Loetscher H, Freskgård P-O, Collin L (2017) Region-specific permeability of the blood-brain barrier upon pericyte loss. J Cereb Blood Flow Metab 37:3683–3694
pubmed: 28273726
pmcid: 5718326
doi: 10.1177/0271678X17697340
Wang Y, Cho C, Williams J, Smallwood PM, Zhang C, Junge HJ, Nathans J (2018) Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood-brain barrier and blood-retina barrier development and maintenance. Proc Natl Acad Sci 115:E11827–E11836
pubmed: 30478038
pmcid: 6294914
Wang Y, Sabbagh MF, Gu X, Rattner A, Williams J, Nathans J (2019) Beta-catenin signaling regulates barrier-specific gene expression in circumventricular organ and ocular vasculatures. elife 8:3221
Warth A, Mittelbronn M, Wolburg H (2005) Redistribution of the water channel protein aquaporin-4 and the K+ channel protein Kir4.1 differs in low- and high-grade human brain tumors. Acta Neuropathol 109:418–426
pubmed: 15723236
doi: 10.1007/s00401-005-0984-x
Watanabe E, Hiyama TY, Shimizu H, Kodama R, Hayashi N, Miyata S, Yanagawa Y, Obata K, Noda M (2006) Sodium-level-sensitive sodium channel Na(x) is expressed in glial laminate processes in the sensory circumventricular organs. Am J Physiol Regul Integr Comp Physiol 290:R568–R576
pubmed: 16223844
doi: 10.1152/ajpregu.00618.2005
Wilhelm I, Nyúl-Tóth Á, Suciu M, Hermenean A, Krizbai IA (2016) Heterogeneity of the blood-brain barrier. Tissue Barriers 4:e1143544–e1143548
pubmed: 27141424
pmcid: 4836475
doi: 10.1080/21688370.2016.1143544
Winkler L, Blasig R, Breitkreuz-Korff O et al (2020) Tight junctions in the blood-brain barrier promote edema formation and infarct size in stroke – ambivalent effects of sealing proteins. J Cereb Blood Flow Metab 89:271678X20904687
Wislocki GB, Leduc EH (1952) Vital staining of the hematoencephalic barrier by silver nitrate and trypan blue, and cytological comparisons of the neurohypophysis, pineal body, area postrema, intercolumnar tubercle and supraoptic crest. J Comp Neurol 96:371–413
pubmed: 14946259
doi: 10.1002/cne.900960302
Wolburg H, Liebner S, Lippoldt A (2003) Freeze-fracture studies of cerebral endothelial tight junctions. Methods Mol Med 89:51–66. https://doi.org/10.1385/1-59259-419-0:51
doi: 10.1385/1-59259-419-0:51
pubmed: 12958412
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
pubmed: 19307424
doi: 10.1177/1073858408329509
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
pubmed: 19533155
doi: 10.1007/s00401-009-0558-4
Yang Y-R, Xiong X-Y, Liu J et al (2017) Mfsd2a (major facilitator superfamily domain containing 2a) attenuates intracerebral hemorrhage-induced blood-brain barrier disruption by inhibiting vesicular transcytosis. J Am Heart Assoc 6:e005811
pubmed: 28724654
pmcid: 5586300
doi: 10.1161/JAHA.117.005811
Yao Y, Chen Z-L, Norris EH, Strickland S (2014) Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity. Nat Commun 5:3413
pubmed: 24583950
doi: 10.1038/ncomms4413
Ye X, Wang Y, Cahill H, Yu M, Badea TC, Smallwood PM, Peachey NS, Nathans J (2009) Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization. Cell 139:285–298
pubmed: 19837032
pmcid: 2779707
doi: 10.1016/j.cell.2009.07.047
Ye X, Smallwood P, Nathans J (2011) Expression of the Norrie disease gene (Ndp) in developing and adult mouse eye, ear, and brain. Gene Expr Patterns 11:151–155
pubmed: 21055480
doi: 10.1016/j.gep.2010.10.007
Yen LF, Wei VC, Kuo EY, Lai TW (2013) Distinct patterns of cerebral extravasation by Evans blue and sodium fluorescein in rats. PLoS One 8:e68595
pubmed: 23861924
pmcid: 3702610
doi: 10.1371/journal.pone.0068595
Zhou Y, Nathans J (2014) Gpr124 controls CNS angiogenesis and blood-brain barrier integrity by promoting ligand-specific canonical wnt signaling. Dev Cell 31:248–256
pubmed: 25373781
pmcid: 4223636
doi: 10.1016/j.devcel.2014.08.018
Zhou Y, Wang Y, Tischfield M, Williams J, Smallwood PM, Rattner A, Taketo MM, Nathans J (2014) Canonical WNT signaling components in vascular development and barrier formation. J Clin Invest 124:3825–3846
pubmed: 25083995
pmcid: 4151216
doi: 10.1172/JCI76431
Ziegler N, Awwad K, Fisslthaler B et al (2016) β-Catenin is required for endothelial Cyp1b1 regulation influencing metabolic barrier function. J Neurosci 36:8921–8935
pubmed: 27559173
pmcid: 6601905
doi: 10.1523/JNEUROSCI.0148-16.2016
Zonta M, Angulo MC, Gobbo S, Rosengarten B, Hossmann K-A, Pozzan T, Carmignoto G (2003) Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci 6:43–50
pubmed: 12469126
doi: 10.1038/nn980