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Fluids and Barriers of the CNS
Published in: Fluids and Barriers of the CNS 1/2018

Open Access 01-12-2018 | Review

Brain vascular heterogeneity: implications for disease pathogenesis and design of in vitro blood–brain barrier models

Authors: Midrelle E. Noumbissi, Bianca Galasso, Monique F. Stins

Published in: Fluids and Barriers of the CNS | Issue 1/2018

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Abstract

The vertebrate blood–brain barrier (BBB) is composed of cerebral microvascular endothelial cells (CEC). The BBB acts as a semi-permeable cellular interface that tightly regulates bidirectional molecular transport between blood and the brain parenchyma in order to maintain cerebral homeostasis. The CEC phenotype is regulated by a variety of factors, including cells in its immediate environment and within functional neurovascular units. The cellular composition of the brain parenchyma surrounding the CEC varies between different brain regions; this difference is clearly visible in grey versus white matter. In this review, we discuss evidence for the existence of brain vascular heterogeneity, focusing on differences between the vessels of the grey and white matter. The region-specific differences in the vasculature of the brain are reflective of specific functions of those particular brain areas. This BBB-endothelial heterogeneity may have implications for the course of pathogenesis of cerebrovascular diseases and neurological disorders involving vascular activation and dysfunction. This heterogeneity should be taken into account when developing BBB-neuro-disease models representative of specific brain areas.
Literature
1.
Abbott NJ. Blood–brain barrier structure and function and the challenges for CNS drug delivery. J Inherit Metabol Dis. 2013;36:437–49.CrossRef
2.
Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ. Structure and function of the blood–brain barrier. Neurobiol Dis. 2010;37:13–25.PubMedCrossRef
3.
Hazleton JE, Berman JW, Eugenin EA. Novel mechanisms of central nervous system damage in HIV infection. HIV AIDS. 2010;2:39–49.
4.
Wolburg H, Wolburg-Buchholz K, Engelhardt B. Diapedesis of mononuclear cells across cerebral venules during experimental autoimmune encephalomyelitis leaves tight junctions intact. Acta Neuropathol. 2005;109:181–90.PubMedCrossRef
5.
Lok J, Gupta P, Guo S, Kim WJ, Whalen MJ, van Leyen K, et al. Cell–cell signaling in the neurovascular unit. Neurochem Res. 2007;32:2032–45.PubMedCrossRef
6.
7.
Abbott NJ, Ronnback L, Hansson E. Astrocyte-endothelial interactions at the blood–brain barrier. Nat Rev Neurosci. 2006;7:41–53.PubMedCrossRef
8.
Hawkins BT, Davis TP. The blood–brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005;57:173–85.PubMedCrossRef
9.
10.
Lok J, Wang XS, Xing CH, Maki TK, Wu LM, Guo SZ, et al. Targeting the neurovascular unit in brain trauma. CNS Neurosci Ther. 2015;21:304–8.PubMedCrossRef
11.
12.
Zonta M, Angulo MC, Gobbo S, Rosengarten B, Hossmann K-A, Pozzan T, et al. Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci. 2003;6:43–50.PubMedCrossRef
13.
Iadecola C, Nedergaard M. Glial regulation of the cerebral microvasculature. Nat Neurosci. 2007;10:1369.PubMedCrossRef
14.
J-m Zhang, H-k Wang, C-q Ye, Ge W, Chen Y, Z-l Jiang, et al. ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron. 2003;40:971–82.CrossRef
15.
Oliet SH, Piet R, Poulain DA. Control of glutamate clearance and synaptic efficacy by glial coverage of neurons. Science. 2001;292:923–6.PubMedCrossRef
16.
Perea G, Navarrete M, Araque A. Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci. 2009;32:421–31.PubMedCrossRef
17.
Suh SW, Bergher JP, Anderson CM, Treadway JL, Fosgerau K, Swanson RA. Astrocyte glycogen sustains neuronal activity during hypoglycemia: studies with the glycogen phosphorylase inhibitor CP-316,819 ([RR*, S*]-5-chloro-N-[2-hydroxy-3-(methoxymethylamino)-3-oxo-1-(phenylmethyl) propyl]-1H-indole-2-carboxamide). J Pharmacol Exp Ther. 2007;321:45–50.PubMedCrossRef
18.
19.
Higashi K, Fujita A, Inanobe A, Tanemoto M, Doi K, Kubo T, et al. An inwardly rectifying K+ channel, Kir4. 1, expressed in astrocytes surrounds synapses and blood vessels in brain. Am J Physiol Cell Physiol. 2001;281:922–31.CrossRef
20.
Simard M, Nedergaard M. The neurobiology of glia in the context of water and ion homeostasis. Neuroscience. 2004;129:877–96.PubMedCrossRef
21.
Rubin LL, Hall DE, Porter S, Barbu K, Cannon C, Horner HC, et al. A cell culture model of the blood–brain barrier. J Cell Biol. 1991;115:1725–35.PubMedCrossRef
22.
Deli MA, Abraham CS, Kataoka Y, Niwa M. Permeability studies on in vitro blood–brain barrier models: physiology, pathology, and pharmacology. Cell Mol Neurobiol. 2005;25:59–127.PubMedCrossRef
23.
24.
25.
Wolburg H, Neuhaus J, Kniesel U, Krauß B, Schmid E-M, Ocalan M, et al. Modulation of tight junction structure in blood–brain barrier endothelial cells. Effects of tissue culture, second messengers and cocultured astrocytes. J Cell Sci. 1994;107:1347–57.PubMed
26.
Volgina N, Gurina O, Grinenko N, Baklaushev V, Ivanova N, Chekhonin V. Expression of tight junction proteins by umbilical vein epithelial cells co-cultured with allogenic astrocytes. Bull Exp Biol Med. 2012;154:124–9.PubMedCrossRef
27.
Risau W, Hallmann R, Albrecht U, Henke-Fahle S. Brain induces the expression of an early cell surface marker for blood–brain barrier-specific endothelium. EMBO J. 1986;5:3179.PubMedPubMedCentralCrossRef
28.
Sun D, Lytle C, O’Donnell ME. Astroglial cell-induced expression of Na–K–Cl cotransporter in brain microvascular endothelial cells. Am J Physiol Cell Physiol. 1995;269:C1506–12.CrossRef
29.
O’Donnell ME, Martinez A, Sun D. Cerebral microvascular endothelial cell Na–K–Cl cotransport: regulation by astrocyte-conditioned medium. Am J Physiol. 1995;268:C747–54.PubMedCrossRef
30.
Chishty M, Reichel A, Begley D, Abbott N. Glial induction of blood–brain barrier-like L-system amino acid transport in the ECV304 cell line. Glia. 2002;39:99–104.PubMedCrossRef
31.
Igarashi Y, Utsumi H, Chiba H, Yamada-Sasamori Y, Tobioka H, Kamimura Y, et al. Glial cell line-derived neurotrophic factor induces barrier function of endothelial cells forming the blood–brain barrier. Biochem Biophys Res Commun. 1999;261:108–12.PubMedCrossRef
32.
Siddharthan V, Kim YV, Liu S, Kim KS. Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells. Brain Res. 2007;1147:39–50.PubMedPubMedCentralCrossRef
33.
Kong L, Wang Y, Wang XJ, Wang XT, Zhao Y, Wang LM, et al. Retinoic acid ameliorates blood–brain barrier disruption following ischemic stroke in rats. Pharmacol Res. 2015;99:125–36.PubMedCrossRef
34.
Argaw AT, Gurfein BT, Zhang Y, Zameer A, John GR. VEGF-mediated disruption of endothelial CLN-5 promotes blood–brain barrier breakdown. Proc Natl Acad Sci USA. 2009;106:1977–82.PubMedPubMedCentralCrossRef
35.
Argaw AT, Asp L, Zhang J, Navrazhina K, Pham T, Mariani JN, et al. Astrocyte-derived VEGF-A drives blood–brain barrier disruption in CNS inflammatory disease. J Clin Invest. 2012;122:2454–68.PubMedPubMedCentralCrossRef
36.
Li YN, Pan R, Qin XJ, Yang WL, Qi Z, Liu W, et al. Ischemic neurons activate astrocytes to disrupt endothelial barrier via increasing VEGF expression. J Neurochem. 2014;129:120–9.PubMedCrossRef
37.
Balabanov R, Dore-Duffy P. Role of the CNS microvascular pericyte in the blood–brain barrier. J Neurosci Res. 1998;53:637–44.PubMedCrossRef
38.
39.
Nakagawa S, Deli MA, Nakao S, Honda M, Hayashi K, Nakaoke R, et al. Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells. Cell Mol Neurobiol. 2007;27:687–94.PubMedCrossRef
40.
Nakagawa S, Deli MA, Kawaguchi H, Shimizudani T, Shimono T, Kittel A, et al. A new blood–brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes. Neurochem Int. 2009;54:253–63.PubMedCrossRef
41.
42.
Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R, et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron. 2010;68:409–27.PubMedPubMedCentralCrossRef
43.
Armulik A, Genove G, Mae M, Nisancioglu MH, Wallgard E, Niaudet C, et al. Pericytes regulate the blood–brain barrier. Nature. 2010;468:557–61.PubMedCrossRef
44.
Villasenor R, Kuennecke B, Ozmen L, Ammann M, Kugler C, Gruninger F, et al. Region-specific permeability of the blood–brain barrier upon pericyte loss. J Cereb Blood Flow Metab. 2017;37:3683–94.PubMedCrossRefPubMedCentral
45.
46.
Chan W, Kohsaka S, Rezaie P. The origin and cell lineage of microglia—new concepts. Brain Res Rev. 2007;53:344–54.PubMedCrossRef
47.
Cuadros MA, Navascués J. The origin and differentiation of microglial cells during development. Prog Neurobiol. 1998;56:173–89.PubMedCrossRef
48.
Crotti A, Ransohoff RM. Microglial physiology and pathophysiology: insights from genome-wide transcriptional profiling. Immunity. 2016;44:505–15.PubMedCrossRef
49.
Stankovic ND, Teodorczyk M, Ploen R, Zipp F, Schmidt MH. Microglia–blood vessel interactions: a double-edged sword in brain pathologies. Acta Neuropathol. 2016;131:347–63.CrossRef
50.
Ravizza T, Gagliardi B, Noe F, Boer K, Aronica E, Vezzani A. Innate and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy. Neurobiol Dis. 2008;29:142–60.PubMedCrossRef
51.
Morin-Brureau M, Lebrun A, Rousset MC, Fagni L, Bockaert J, de Bock F, et al. Epileptiform activity induces vascular remodeling and zonula occludens 1 downregulation in organotypic hippocampal cultures: role of VEGF signaling pathways. J Neurosci. 2011;31:10677–88.PubMedCrossRefPubMedCentral
52.
Librizzi L, Noe F, Vezzani A, de Curtis M, Ravizza T. Seizure-induced brain-borne inflammation sustains seizure recurrence and blood–brain barrier damage. Ann Neurol. 2012;72:82–90.PubMedCrossRef
53.
Lo EH, Broderick JP, Moskowitz MA. tPA and proteolysis in the neurovascular unit. Stroke. 2004;35:354–6.PubMedCrossRef
54.
Guo S, Kim WJ, Lok J, Lee SR, Besancon E, Luo BH, et al. Neuroprotection via matrix-trophic coupling between cerebral endothelial cells and neurons. Proc Natl Acad Sci USA. 2008;105:7582–7.PubMedPubMedCentralCrossRef
55.
Arai K, Lo EH. An oligovascular niche: cerebral Endothelial cells promote the survival and proliferation of oligodendrocyte precursor cells. J Neurosci. 2009;29:4351–5.PubMedPubMedCentralCrossRef
56.
Iijima K, Kurachi M, Shibasaki K, Naruse M, Puentes S, Imai H, et al. Transplanted microvascular endothelial cells promote oligodendrocyte precursor cell survival in ischemic demyelinating lesions. J Neurochem. 2015;135:539–50.PubMedCrossRef
57.
Kurachi M, Mikuni M, Ishizaki Y. Extracellular vesicles from vascular endothelial cells promote survival, proliferation and motility of oligodendrocyte precursor cells. PLoS ONE. 2016;11:e0159158.PubMedPubMedCentralCrossRef
58.
Zobel K, Hansen U, Galla H-J. Blood–brain barrier properties in vitro depend on composition and assembly of endogenous extracellular matrices. Cell Tissue Res. 2016;365:233–45.PubMedCrossRef
59.
60.
Thyboll J, Kortesmaa J, Cao R, Soininen R, Wang L, Iivanainen A, et al. Deletion of the laminin alpha4 chain leads to impaired microvessel maturation. Mol Cell Biol. 2002;22:1194–202.PubMedPubMedCentralCrossRef
61.
Menezes MJ, McClenahan FK, Leiton CV, Aranmolate A, Shan X, Colognato H. The extracellular matrix protein laminin α2 regulates the maturation and function of the blood–brain barrier. J Neurosci. 2014;34:15260–80.PubMedCrossRefPubMedCentral
62.
Yao Y, Chen Z-L, Norris EH, Strickland S. Astrocytic laminin regulates pericyte differentiation and maintains blood brain barrier integrity. Nat Commun. 2014;5:3413.PubMedCrossRef
63.
64.
Kangwantas K, Pinteaux E, Penny J. The extracellular matrix protein laminin-10 promotes blood–brain barrier repair after hypoxia and inflammation in vitro. J Neuroinflammation. 2016;13:25.PubMedPubMedCentralCrossRef
65.
Costell M, Gustafsson E, Aszódi A, Mörgelin M, Bloch W, Hunziker E, et al. Perlecan maintains the integrity of cartilage and some basement membranes. J Cell Biol. 1999;147:1109–22.PubMedPubMedCentralCrossRef
66.
Pöschl E, Schlötzer-Schrehardt U, Brachvogel B, Saito K, Ninomiya Y, Mayer U. Collagen IV is essential for basement membrane stability but dispensable for initiation of its assembly during early development. Development. 2004;131:1619–28.PubMedCrossRef
67.
Izawa Y, Gu Y-H, Osada T, Kanazawa M, Hawkins BT, Koziol JA, et al. β1-integrin–matrix interactions modulate cerebral microvessel endothelial cell tight junction expression and permeability. J Cereb Blood Flow Metab. 2017;38(4):641–58.PubMedCrossRefPubMedCentral
68.
Osada T, Gu Y-H, Kanazawa M, Tsubota Y, Hawkins BT, Spatz M, et al. Interendothelial claudin-5 expression depends on cerebral endothelial cell–matrix adhesion by β1-integrins. J Cereb Blood Flow Metab. 2011;31:1972–85.PubMedPubMedCentralCrossRef
69.
Sado Y, Kagawa M, Kishiro Y, Sugihara K, Naito I, Seyer JM, et al. Establishment by the rat lymph node method of epitope-defined monoclonal antibodies recognizing the six different alpha chains of human type IV collagen. Histochem Cell Biol. 1995;104:267–75.PubMedCrossRef
70.
Gould DB, Phalan FC, Breedveld GJ, van Mil SE, Smith RS, Schimenti JC, et al. Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly. Science. 2005;308:1167–71.PubMedCrossRef
71.
Gould DB, Phalan FC, van Mil SE, Sundberg JP, Vahedi K, Massin P, et al. Role of COL4A1 in small-vessel disease and hemorrhagic stroke. N Engl J Med. 2006;354:1489–96.PubMedCrossRef
72.
Breedveld G, de Coo IF, Lequin MH, Arts WF, Heutink P, Gould DB, et al. Novel mutations in three families confirm a major role of COL4A1 in hereditary porencephaly. J Med Genet. 2006;43:490–5.PubMedCrossRef
73.
Vahedi K, Kubis N, Boukobza M, Arnoult M, Massin P, Tournier-Lasserve E, et al. COL4A1 mutation in a patient with sporadic, recurrent intracerebral hemorrhage. Stroke. 2007;38:1461–4.PubMedCrossRef
74.
Lichtenbelt KD, Pistorius LR, De Tollenaer SM, Mancini GM, De Vries LS. Prenatal genetic confirmation of a COL4A1 mutation presenting with sonographic fetal intracranial hemorrhage. Ultrasound Obstet Gynecol. 2012;39:726–7.PubMedCrossRef
75.
Weng YC, Sonni A, Labelle-Dumais C, de Leau M, Kauffman WB, Jeanne M, et al. COL4A1 mutations in patients with sporadic late-onset intracerebral hemorrhage. Ann Neurol. 2012;71:470–7.PubMedPubMedCentralCrossRef
76.
Jeanne M, Labelle-Dumais C, Jorgensen J, Kauffman WB, Mancini GM, Favor J, et al. COL4A2 mutations impair COL4A1 and COL4A2 secretion and cause hemorrhagic stroke. Am J Hum Genet. 2012;90:91–101.PubMedPubMedCentralCrossRef
77.
Verbeek E, Meuwissen ME, Verheijen FW, Govaert PP, Licht DJ, Kuo DS, et al. COL4A2 mutation associated with familial porencephaly and small-vessel disease. Eur J Hum Genet. 2012;20:844–51.PubMedPubMedCentralCrossRef
78.
Yoneda Y, Haginoya K, Arai H, Yamaoka S, Tsurusaki Y, Doi H, et al. De novo and inherited mutations in COL4A2, encoding the type IV collagen alpha2 chain cause porencephaly. Am J Hum Genet. 2012;90:86–90.PubMedPubMedCentralCrossRef
79.
Sibon I, Coupry I, Menegon P, Bouchet JP, Gorry P, Burgelin I, et al. COL4A1 mutation in Axenfeld–Rieger anomaly with leukoencephalopathy and stroke. Ann Neurol. 2007;62:177–84.PubMedCrossRef
80.
Vahedi K, Boukobza M, Massin P, Gould DB, Tournier-Lasserve E, Bousser MG. Clinical and brain MRI follow-up study of a family with COL4A1 mutation. Neurology. 2007;69:1564–8.PubMedCrossRef
81.
Plaisier E, Gribouval O, Alamowitch S, Mougenot B, Prost C, Verpont MC, et al. COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. N Engl J Med. 2007;357:2687–95.PubMedCrossRef
82.
Alamowitch S, Plaisier E, Favrole P, Prost C, Chen Z, Van Agtmael T, et al. Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. Neurology. 2009;73:1873–82.PubMedPubMedCentralCrossRef
83.
Shah S, Kumar Y, McLean B, Churchill A, Stoodley N, Rankin J, et al. A dominantly inherited mutation in collagen IV A1 (COL4A1) causing childhood onset stroke without porencephaly. Eur J Paediatr Neurol. 2010;14:182–7.PubMedCrossRef
84.
Rouaud T, Labauge P, Tournier Lasserve E, Mine M, Coustans M, Deburghgraeve V, et al. Acute urinary retention due to a novel collagen COL4A1 mutation. Neurology. 2010;75:747–9.PubMedCrossRef
85.
Plaisier E, Chen Z, Gekeler F, Benhassine S, Dahan K, Marro B, et al. Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple helical CB3[IV] domain. Am J Med Genet A. 2010;152A:2550–5.PubMedCrossRef
86.
Livingston J, Doherty D, Orcesi S, Tonduti D, Piechiecchio A, La Piana R, et al. COL4A1 mutations associated with a characteristic pattern of intracranial calcification. Neuropediatrics. 2011;42:227–33.PubMedCrossRef
87.
Shah S, Ellard S, Kneen R, Lim M, Osborne N, Rankin J, et al. Childhood presentation of COL4A1 mutations. Dev Med Child Neurol. 2012;54:569–74.PubMedCrossRef
88.
McConnell HL, Kersch CN, Woltjer RL, Neuwelt EA. The translational significance of the neurovascular unit. J Biol Chem. 2017;292:762–70.PubMedCrossRef
89.
Joutel A, Haddad I, Ratelade J, Nelson MT. Perturbations of the cerebrovascular matrisome: a convergent mechanism in small vessel disease of the brain? J Cereb Blood Flow Metab. 2016;36:143–57.PubMedPubMedCentralCrossRef
90.
Szklarczyk A, Stins M, Milward E, Ryu H, Fitzsimmons C, Sullivan D, et al. Glial activation and matrix metalloproteinase release in cerebral malaria. J Neurovirol. 2007;13:2–10.PubMedCrossRef
91.
Polimeni M, Prato M. Host matrix metalloproteinases in cerebral malaria: new kids on the block against blood–brain barrier integrity? Fluids Barriers CNS. 2014;11:1.PubMedPubMedCentralCrossRef
92.
93.
Rosenberg G, Estrada E, Dencoff J. Matrix metalloproteinases and TIMPs are associated with blood–brain barrier opening after reperfusion in rat brain. Stroke. 1998;29:2189–95.PubMedCrossRef
94.
Zozulya A, Weidenfeller C, Galla H-J. Pericyte–endothelial cell interaction increases MMP-9 secretion at the blood–brain barrier in vitro. Brain Res. 2008;1189:1–11.PubMedCrossRef
95.
Azevedo FA, Carvalho LR, Grinberg LT, Farfel JM, Ferretti RE, Leite RE, et al. Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain. J Comp Neurol. 2009;513:532–41.PubMedCrossRef
96.
Nyúl-Tóth Á, Suciu M, Molnár J, Fazakas C, Haskó J, Herman H, et al. Differences in the molecular structure of the blood–brain barrier in the cerebral cortex and white matter: an in silico, in vitro, and ex vivo study. Am J Physiol Heart Circ Physiol. 2016;310:H1702–14.PubMedCrossRef
97.
Liu H, Yang Y, Xia Y, Zhu W, Leak RK, Wei Z, et al. Aging of cerebral white matter. Ageing Res Rev. 2017;34:64–76.PubMedCrossRef
98.
99.
100.
Eyal S, Ke B, Muzi M, Link JM, Mankoff DA, Collier AC, et al. Regional P-glycoprotein activity and inhibition at the human blood–brain barrier as imaged by positron emission tomography. Clin Pharmacol Ther. 2010;87:579–85.PubMedCrossRef
101.
de Graaf RA, Pan JW, Telang F, Lee JH, Brown P, Novotny EJ, et al. Differentiation of glucose transport in human brain gray and white matter. J Cereb Blood Flow Metab. 2001;21:483–92.PubMedCrossRef
102.
Cavaglia M, Dombrowski SM, Drazba J, Vasanji A, Bokesch PM, Janigro D. Regional variation in brain capillary density and vascular response to ischemia. Brain Res. 2001;910:81–93.PubMedCrossRef
103.
El-Khoury N, Braun A, Hu F, Pandey M, Nedergaard M, Lagamma EF, et al. Astrocyte end-feet in germinal matrix, cerebral cortex, and white matter in developing infants. Pediatr Res. 2006;59:673–9.PubMedCrossRef
104.
Hanske S, Dyrna F, Bechmann I, Krueger M. Different segments of the cerebral vasculature reveal specific endothelial specifications, while tight junction proteins appear equally distributed. Brain Struct Funct. 2017;222:1179–92.PubMedCrossRef
105.
Macdonald JA, Murugesan N, Pachter JS. Endothelial cell heterogeneity of blood–brain barrier gene expression along the cerebral microvasculature. J Neurosci Res. 2010;88:1457–74.PubMed
106.
Allt G, Lawrenson JG. Is the pial microvessel a good model for blood–brain barrier studies? Brain Res Brain Res Rev. 1997;24:67–76.PubMedCrossRef
107.
Lawrenson JG, Reid AR, Finn TM, Orte C, Allt G. Cerebral and pial microvessels: differential expression of gamma-glutamyl transpeptidase and alkaline phosphatase. Anat Embryol. 1999;199:29–34.CrossRef
108.
109.
Lund H, Krakauer M, Skimminge A, Sellebjerg F, Garde E, Siebner HR, et al. blood–brain barrier permeability of normal appearing white matter in relapsing-remitting multiple sclerosis. PLoS ONE. 2013;8:e56375.PubMedPubMedCentralCrossRef
110.
Kivisäkk P, Mahad DJ, Callahan MK, Trebst C, Tucky B, Wei T, et al. Human cerebrospinal fluid central memory CD4+T cells: evidence for trafficking through choroid plexus and meninges via P-selectin. Proc Natl Acad Sci USA. 2003;100:8389–94.PubMedPubMedCentralCrossRef
111.
Kent SJ, Karlik SJ, Cannon C, Hines DK, Yednock TA, Fritz LC, et al. A monoclonal antibody to α4 integrin suppresses and reverses active experimental allergic encephalomyelitis. J Neuroimmunol. 1995;58:1–10.PubMedCrossRef
112.
Theien BE, Vanderlugt CL, Eagar TN, Nickerson-Nutter C, Nazareno R, Kuchroo VK, et al. Discordant effects of anti-VLA-4 treatment before and after onset of relapsing experimental autoimmune encephalomyelitis. J Clin Invest. 2001;107:995–1006.PubMedPubMedCentralCrossRef
113.
Tubridy N, Behan P, Capildeo R, Chaudhuri A, Forbes R, Hawkins C, et al. The effect of anti-α4 integrin antibody on brain lesion activity in MS. Neurology. 1999;53:466.PubMedCrossRef
114.
Welsh CT, Rose JW, Hill KE, Townsend JJ. Augmentation of adoptively transferred experimental allergic encephalomyelitis by administration of a monoclonal antibody specific for LFA-1α. J Neuroimmunol. 1993;43:161–7.PubMedCrossRef
115.
Holley JE, Newcombe J, Whatmore JL, Gutowski NJ. Increased blood vessel density and endothelial cell proliferation in multiple sclerosis cerebral white matter. Neurosci Lett. 2010;470:65–70.PubMedCrossRef
116.
van Horssen J, Brink BP, de Vries HE, van der Valk P, Bø L. The blood–brain barrier in cortical multiple sclerosis lesions. J Neuropathol Exp Neurol. 2007;66:321–8.PubMedCrossRef
117.
Prins M, Schul E, Geurts J, van der Valk P, Drukarch B, van Dam A-M. Pathological differences between white and grey matter multiple sclerosis lesions. Ann N Y Acad Sci. 2015;1351:99–113.PubMedCrossRef
118.
Buschmann JP, Berger K, Awad H, Clarner T, Beyer C, Kipp M. Inflammatory response and chemokine expression in the white matter corpus callosum and gray matter cortex region during cuprizone-induced demyelination. J Mol Neurosci. 2012;48:66–76.PubMedPubMedCentralCrossRef
119.
Gudi V, Moharregh-Khiabani D, Skripuletz T, Koutsoudaki PN, Kotsiari A, Skuljec J, et al. Regional differences between grey and white matter in cuprizone induced demyelination. Brain Res. 2009;1283:127–38.PubMedCrossRef
120.
Janssen K, Rickert M, Clarner T, Beyer C, Kipp M. Absence of CCL2 and CCL3 ameliorates central nervous system grey matter but not white matter demyelination in the presence of an intact blood–brain barrier. Mol Neurobiol. 2016;53:1551–64.PubMedCrossRef
121.
Samartzis L, Dima D, Fusar-Poli P, Kyriakopoulos M. White matter alterations in early stages of schizophrenia: a systematic review of diffusion tensor imaging studies. J Neuroimaging. 2014;24:101–10.PubMedCrossRef
122.
Downhill JE, Buchsbaum MS, Wei T, Spiegel-Cohen J, Hazlett EA, Haznedar MM, et al. Shape and size of the corpus callosum in schizophrenia and schizotypal personality disorder. Schizophr Res. 2000;42:193–208.PubMedCrossRef
123.
Bachmann S, Pantel J, Flender A, Bottmer C, Essig M, Schröder J. Corpus callosum in first-episode patients with schizophrenia–A magnetic resonance imaging study. Psychol Med. 2003;33:1019–27.PubMedCrossRef
124.
Reis Marques T, Taylor H, Chaddock C, Dell’Acqua F, Handley R, Reinders AS, et al. White matter integrity as a predictor of response to treatment in first episode psychosis. Brain. 2013;137:172–82.PubMedPubMedCentralCrossRef
125.
Davis KL, Stewart DG, Friedman JI, Buchsbaum M, Harvey PD, Hof PR, et al. White matter changes in schizophrenia: evidence for myelin-related dysfunction. Arch Gen Psychiatry. 2003;60:443–56.PubMedCrossRef
126.
Hercher C, Chopra V, Beasley CL. Evidence for morphological alterations in prefrontal white matter glia in schizophrenia and bipolar disorder. J Psychiatry Neurosci. 2014;39:376–85.PubMedPubMedCentralCrossRef
127.
Rao JS, Kim H-W, Harry GJ, Rapoport SI, Reese EA. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in the postmortem frontal cortex from schizophrenia patients. Schizophr Res. 2013;147:24–31.PubMedCrossRef
128.
Kettenmann H, Hanisch U-K, Noda M, Verkhratsky A. Physiology of microglia. Physiol Rev. 2011;91:461–553.PubMedCrossRef
129.
Fillman S, Cloonan N, Catts V, Miller L, Wong J, McCrossin T, et al. Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry. 2013;18:206–14.PubMedCrossRef
130.
Pasternak O, Westin C-F, Bouix S, Seidman LJ, Goldstein JM, Woo T-UW, et al. Excessive extracellular volume reveals a neurodegenerative pattern in schizophrenia onset. J Neurosci. 2012;32:17365–72.PubMedPubMedCentralCrossRef
131.
Milleit B, Smesny S, Rothermundt M, Preul C, Schroeter ML, von Eiff C, et al. Serum S100B protein is specifically related to white matter changes in schizophrenia. Front Cell Neurosci. 2016;10:33.PubMedPubMedCentralCrossRef
132.
133.
Persidsky Y, Ghorpade A, Rasmussen J, Limoges J, Liu XJ, Stins M, et al. Microglial and astrocyte chemokines regulate monocyte migration through the blood–brain barrier in human immunodeficiency virus-1 encephalitis. Am J Pathol. 1999;155:1599–611.PubMedPubMedCentralCrossRef
134.
Stins MF, Pearce D, Di Cello F, Erdreich-Epstein A, Pardo CA, Kim KS. Induction of intercellular adhesion molecule-1 on human brain endothelial cells by HIV-1 gp120: role of CD4 and chemokine coreceptors. Lab Invest. 2003;83:1787–98.PubMedCrossRef
135.
Navia BA, Cho ES, Petito CK, Price RW. The AIDS dementia complex: II. Neuropathology. Ann Neurol. 1986;19:525–35.PubMedCrossRef
136.
Wiley CA, Masliah E, Morey M, Lemere C, DeTeresa R, Grafe M, et al. Neocortical damage during HIV infection. Ann Neurol. 1991;29:651–7.PubMedCrossRef
137.
Dallasta LM, Pisarov LA, Esplen JE, Werley JV, Moses AV, Nelson JA, et al. Blood–brain barrier tight junction disruption in human immunodeficiency virus-1 encephalitis. Am J Pathol. 1999;155:1915–27.PubMedPubMedCentralCrossRef
138.
Medana IM, Turner GD. Human cerebral malaria and the blood–brain barrier. Int J Parasitol. 2006;36:555–68.PubMedCrossRef
139.
Brown H, Hien TT, Day N, Mai NT, Chuong LV, Chau TT, et al. Evidence of blood–brain barrier dysfunction in human cerebral malaria. Neuropathol Appl Neurobiol. 1999;25:331–40.PubMedCrossRef
140.
Turner GD, Morrison H, Jones M, Davis TM, Looareesuwan S, Buley ID, et al. An immunohistochemical study of the pathology of fatal malaria. Evidence for widespread endothelial activation and a potential role for intercellular adhesion molecule-1 in cerebral sequestration. Am J Pathol. 1994;145:1057–69.PubMedPubMedCentral
141.
Ponsford MJ, Medana IM, Prapansilp P, Hien TT, Lee SJ, Dondorp AM, et al. Sequestration and microvascular congestion are associated with coma in human cerebral malaria. J Infect Dis. 2012;205:663–71.PubMedCrossRef
142.
Hunt NH, Golenser J, Chan-Ling T, Parekh S, Rae C, Potter S, et al. Immunopathogenesis of cerebral malaria. Int J Parasitol. 2006;36:569–82.PubMedCrossRef
143.
Brown H, Rogerson S, Taylor T, Tembo M, Mwenechanya J, Molyneux M, et al. Blood–brain barrier function in cerebral malaria in Malawian children. Am J Trop Med Hyg. 2001;64:207–13.PubMedCrossRef
144.
Moxon CA, Wassmer SC, Milner DA, Chisala NV, Taylor TE, Seydel KB, et al. Loss of endothelial protein C receptors links coagulation and inflammation to parasite sequestration in cerebral malaria in African children. Blood. 2013;122:842–51.PubMedPubMedCentralCrossRef
145.
MacPherson GG, Warrell MJ, White NJ, Looareesuwan S, Warrell DA. Human cerebral malaria. A quantitative ultrastructural analysis of parasitized erythrocyte sequestration. Am J Pathol. 1985;119:385–401.PubMedPubMedCentral
146.
Dorovini-Zis K, Schmidt K, Huynh H, Fu W, Whitten RO, Milner D, et al. The neuropathology of fatal cerebral malaria in malawian children. Am J Pathol. 2011;178:2146–58.PubMedPubMedCentralCrossRef
147.
Taylor TE, Fu WJ, Carr RA, Whitten RO, Mueller JS, Fosiko NG, et al. Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med. 2004;10:143–5.PubMedCrossRef
148.
Ge S, Song L, Pachter JS. Where is the blood–brain barrier… really? J Neurosci Res. 2005;79:421–7.PubMedCrossRef
149.
Tunkel AR, Rosser SW, Hansen EJ, Scheld WM. Blood–brain barrier alterations in bacterial meningitis: development of an in vitro model and observations on the effects of lipopolysaccharide. In Vitro Cell Dev Biol. 1991;27:113–20.CrossRef
150.
Audus KL, Borchardt RT. Characteristics of the large neutral amino acid transport system of bovine brain microvessel endothelial cell monolayers. J Neurochem. 1986;47:484–8.PubMedCrossRef
151.
Duport S, Robert F, Muller D, Grau G, Parisi L, Stoppini L. An in vitro blood–brain barrier model: cocultures between endothelial cells and organotypic brain slice cultures. Proc Natl Acad Sci USA. 1998;95:1840–5.PubMedPubMedCentralCrossRef
152.
Mukhtar M, Pomerantz RJ. Development of an in vitro blood–brain barrier model to study molecular neuropathogenesis and neurovirologic disorders induced by human immunodeficiency virus type 1 infection. J Hum Virol. 2000;3:324–34.PubMed
153.
Stins MF, Prasadarao NV, Zhou J, Arditi M, Kim KS. Bovine brain microvascular endothelial cells transfected with SV40-large T antigen: development of an immortalized cell line to study pathophysiology of CNS disease. In Vitro Cell Dev Biol Anim. 1997;33:243–7.PubMedCrossRef
154.
Helms HC, Abbott NJ, Burek M, Cecchelli R, Couraud PO, Deli MA, et al. In vitro models of the blood–brain barrier: an overview of commonly used brain endothelial cell culture models and guidelines for their use. J Cereb Blood Flow Metab. 2016;36:862–90.PubMedPubMedCentralCrossRef
155.
Kusch-Poddar M, Drewe J, Fux I, Gutmann H. Evaluation of the immortalized human brain capillary endothelial cell line BB19 as a human cell culture model for the blood–brain barrier. Brain Res. 2005;1064:21–31.PubMedCrossRef
156.
Eigenmann DE, Xue G, Kim KS, Moses AV, Hamburger M, Oufir M. Comparative study of four immortalized human brain capillary endothelial cell lines, hCMEC/D3, hBMEC, TY10, and BB19, and optimization of culture conditions, for an in vitro blood–brain barrier model for drug permeability studies. Fluids Barriers CNS. 2013;10:33.PubMedPubMedCentralCrossRef
157.
Paolinelli R, Corada M, Ferrarini L, Devraj K, Artus C, Czupalla CJ, et al. Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro. PLoS ONE. 2013;8:e70233.PubMedPubMedCentralCrossRef
158.
Weksler B, Subileau E, Perriere N, Charneau P, Holloway K, Leveque M, et al. blood–brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J. 2005;19:1872–4.PubMedCrossRef
159.
160.
Katt ME, Xu ZS, Gerecht S, Searson PC. Human brain microvascular endothelial cells derived from the BC1 iPS cell line exhibit a blood–brain barrier phenotype. PLoS ONE. 2016;11:e0152105.PubMedPubMedCentralCrossRef
161.
Lippmann ES, Al-Ahmad A, Azarin SM, Palecek SP, Shusta EV. A retinoic acid-enhanced, multicellular human blood–brain barrier model derived from stem cell sources. Sci Rep. 2014;4:4160.PubMedPubMedCentralCrossRef
162.
Lippmann ES, Azarin SM, Kay JE, Nessler RA, Wilson HK, Al-Ahmad A, et al. Human blood–brain barrier endothelial cells derived from pluripotent stem cells. Nat Biotechnol. 2012;30:783–91.PubMedPubMedCentralCrossRef
163.
Page S, Munsell A, Al-Ahmad AJ. Cerebral hypoxia/ischemia selectively disrupts tight junctions complexes in stem cell-derived human brain microvascular endothelial cells. Fluids Barriers CNS. 2016;13:16.PubMedPubMedCentralCrossRef
164.
Yamamizu K, Iwasaki M, Takakubo H, Sakamoto T, Ikuno T, Miyoshi M, et al. In vitro modeling of blood–brain barrier with human iPSC-derived endothelial cells, pericytes, neurons, and astrocytes via notch signaling. Stem Cell Rep. 2017;8:634–47.CrossRef
165.
Canfield SG, Stebbins MJ, Morales BS, Asai SW, Vatine GD, Svendsen CN, et al. An isogenic blood–brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells. J Neurochem. 2017;140:874–88.PubMedPubMedCentralCrossRef
166.
Hollmann EK, Bailey AK, Potharazu AV, Neely MD, Bowman AB, Lippmann ES. Accelerated differentiation of human induced pluripotent stem cells to blood–brain barrier endothelial cells. Fluids Barriers CNS. 2017;14:9.PubMedPubMedCentralCrossRef
167.
DeStefano JG, Xu ZS, Williams AJ, Yimam N, Searson PC. Effect of shear stress on iPSC-derived human brain microvascular endothelial cells (dhBMECs). Fluids Barriers CNS. 2017;14:20.PubMedPubMedCentralCrossRef
168.
Bowman PD, Ennis SR, Rarey KE, Betz AL, Goldstein GW. Brain microvessel endothelial cells in tissue culture: a model for study of blood–brain barrier permeability. Ann Neurol. 1983;14:396–402.PubMedCrossRef
169.
Cecchelli R, Dehouck B, Descamps L, Fenart L, Buee-Scherrer VV, Duhem C, et al. In vitro model for evaluating drug transport across the blood–brain barrier. Adv Drug Deliv Rev. 1999;36:165–78.PubMedCrossRef
170.
Gaillard PJ, Voorwinden LH, Nielsen JL, Ivanov A, Atsumi R, Engman H, et al. Establishment and functional characterization of an in vitro model of the blood–brain barrier, comprising a co-culture of brain capillary endothelial cells and astrocytes. Eur J Pharm Sci. 2001;12:215–22.PubMedCrossRef
171.
Cohen-Kashi Malina K, Cooper I, Teichberg VI. Closing the gap between the in vivo and in vitro blood–brain barrier tightness. Brain Res. 2009;1284:12–21.PubMedCrossRef
172.
Abbott NJ, Dolman DE, Drndarski S, Fredriksson SM. An improved in vitro blood–brain barrier model: rat brain endothelial cells co-cultured with astrocytes. Methods Mol Biol. 2012;814:415–30.PubMedCrossRef
173.
Boveri M, Berezowski V, Price A, Slupek S, Lenfant AM, Benaud C, et al. Induction of blood–brain barrier properties in cultured brain capillary endothelial cells: comparison between primary glial cells and C6 cell line. Glia. 2005;51:187–98.PubMedCrossRef
174.
Culot M, Lundquist S, Vanuxeem D, Nion S, Landry C, Delplace Y, et al. An in vitro blood–brain barrier model for high throughput (HTS) toxicological screening. Toxicol In Vitro. 2008;22:799–811.PubMedCrossRef
175.
Perriere N, Yousif S, Cazaubon S, Chaverot N, Bourasset F, Cisternino S, et al. A functional in vitro model of rat blood–brain barrier for molecular analysis of efflux transporters. Brain Res. 2007;1150:1–13.PubMedCrossRef
176.
Dohgu S, Takata F, Yamauchi A, Nakagawa S, Egawa T, Naito M, et al. Brain pericytes contribute to the induction and up-regulation of blood–brain barrier functions through transforming growth factor-beta production. Brain Res. 2005;1038:208–15.PubMedCrossRef
177.
Hayashi K, Nakao S, Nakaoke R, Nakagawa S, Kitagawa N, Niwa M. Effects of hypoxia on endothelial/pericytic co-culture model of the blood–brain barrier. Regul Pept. 2004;123:77–83.PubMedCrossRef
178.
Vandenhaute E, Dehouck L, Boucau MC, Sevin E, Uzbekov R, Tardivel M, et al. Modelling the neurovascular unit and the blood–brain barrier with the unique function of pericytes. Curr Neurovasc Res. 2011;8:258–69.PubMedCrossRef
179.
Wilhelm I, Fazakas C, Krizbai IA. In vitro models of the blood–brain barrier. Acta Neurobiol Exp. 2011;71:113–28.
180.
Hatherell K, Couraud PO, Romero IA, Weksler B, Pilkington GJ. Development of a three-dimensional, all-human in vitro model of the blood–brain barrier using mono-, co-, and tri-cultivation transwell models. J Neurosci Methods. 2011;199:223–9.PubMedCrossRef
181.
Watson PMD, Paterson JC, Thom G, Ginman U, Lundquist S, Webster CI. Modelling the endothelial blood-CNS barriers: a method for the production of robust in vitro models of the rat blood–brain barrier and blood–spinal cord barrier. BMC Neurosci. 2013;14:59.PubMedPubMedCentralCrossRef
182.
Helms HC, Waagepetersen HS, Nielsen CU, Brodin B. Paracellular tightness and claudin-5 expression is increased in the BCEC/astrocyte blood–brain barrier model by increasing media buffer capacity during growth. AAPS J. 2010;12:759–70.PubMedPubMedCentralCrossRef
183.
Colgan OC, Collins NT, Ferguson G, Murphy RP, Birney YA, Cahill PA, et al. Influence of basolateral condition on the regulation of brain microvascular endothelial tight junction properties and barrier function. Brain Res. 2008;1193:84–92.PubMedCrossRef
184.
András IE, Toborek M. Extracellular vesicles of the blood–brain barrier. Tissue Barriers. 2016;4:e1131804.PubMedCrossRef
185.
Li YS, Haga JH, Chien S. Molecular basis of the effects of shear stress on vascular endothelial cells. J Biomech. 2005;38:1949–71.PubMedCrossRef
186.
Davies PF. Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology. Nat Clin Pract Cardiovasc Med. 2009;6:16–26.PubMedCrossRef
187.
Cucullo L, Hossain M, Puvenna V, Marchi N, Janigro D. The role of shear stress in blood–brain Barrier endothelial physiology. BMC Neurosci. 2011;12:40.PubMedPubMedCentralCrossRef
188.
Takeshita Y, Obermeier B, Cotleur A, Sano Y, Kanda T, Ransohoff RM. An in vitro blood–brain barrier model combining shear stress and endothelial cell/astrocyte co-culture. J Neurosci Methods. 2014;232:165–72.PubMedPubMedCentralCrossRef
189.
Colgan OC, Ferguson G, Collins NT, Murphy RP, Meade G, Cahill PA, et al. Regulation of bovine brain microvascular endothelial tight junction assembly and barrier function by laminar shear stress. Am J Physiol Heart Circ Physiol. 2007;292:H3190–7.PubMedCrossRef
190.
Partyka PP, Godsey GA, Galie JR, Kosciuk MC, Acharya NK, Nagele RG, et al. Mechanical stress regulates transport in a compliant 3D model of the blood–brain barrier. Biomaterials. 2017;115:30–9.PubMedCrossRef
191.
Garcia-Polite F, Martorell J, Del Rey-Puech P, Melgar-Lesmes P, O’Brien CC, Roquer J, et al. Pulsatility and high shear stress deteriorate barrier phenotype in brain microvascular endothelium. J Cereb Blood Flow Metab. 2017;37:2614–25.PubMedCrossRef
192.
Krizanac-Bengez L, Mayberg MR, Cunningham E, Hossain M, Ponnampalam S, Parkinson FE, et al. Loss of shear stress induces leukocyte-mediated cytokine release and blood–brain barrier failure in dynamic in vitro blood–brain barrier model. J Cell Physiol. 2006;206:68–77.PubMedCrossRef
193.
Galie PA, van Oosten A, Chen CS, Janmey PA. Application of multiple levels of fluid shear stress to endothelial cells plated on polyacrylamide gels. Lab Chip. 2015;15:1205–12.PubMedPubMedCentralCrossRef
194.
Stroka KM, Aranda-Espinoza H. Endothelial cell substrate stiffness influences neutrophil transmigration via myosin light chain kinase-dependent cell contraction. Blood. 2011;118:1632–40.PubMedPubMedCentralCrossRef
195.
Kohn JC, Zhou DW, Bordeleau F, Zhou AL, Mason BN, Mitchell MJ, et al. Cooperative effects of matrix stiffness and fluid shear stress on endothelial cell behavior. Biophys J. 2015;108:471–8.PubMedPubMedCentralCrossRef
196.
Okech W, Abberton KM, Kuebel JM, Hocking DC, Sarelius IH. Extracellular matrix fibronectin mediates an endothelial cell response to shear stress via the heparin-binding, matricryptic RWRPK sequence of FNIII1H. Am J Physiol Heart Circ Physiol. 2016;311:H1071.CrossRef
197.
Orr AW, Sanders JM, Bevard M, Coleman E, Sarembock IJ, Schwartz MA. The subendothelial extracellular matrix modulates NF-kappaB activation by flow: a potential role in atherosclerosis. J Cell Biol. 2005;169:191–202.PubMedPubMedCentralCrossRef
198.
Ye M, Sanchez HM, Hultz M, Yang Z, Bogorad M, Wong AD, et al. Brain microvascular endothelial cells resist elongation due to curvature and shear stress. Sci Rep. 2014;4:4681.PubMedPubMedCentralCrossRef
199.
Bramley JC, Drummond CG, Lennemann NJ, Good CA, Kim KS, Coyne CB. A three-dimensional cell culture system to model RNA virus infections at the blood–brain barrier. mSphere. 2017;2:e00206–17.PubMedPubMedCentralCrossRef
200.
201.
Brown JA, Pensabene V, Markov DA, Allwardt V, Neely MD, Shi M, et al. Recreating blood–brain barrier physiology and structure on chip: a novel neurovascular microfluidic bioreactor. Biomicrofluidics. 2015;9:054124.PubMedPubMedCentralCrossRef
202.
Herland A, van der Meer A, FitzGerald EA, Park T-E, Sleeboom JJF, Ingber DE. Distinct contributions of astrocytes and pericytes to neuroinflammation identified in a 3D human blood–brain barrier on a chip. PLOS ONE. 2016;11:e0150360.PubMedPubMedCentralCrossRef
203.
Griep LM, Wolbers F, de Wagenaar B, ter Braak PM, Weksler BB, Romero IA, et al. BBB on chip: microfluidic platform to mechanically and biochemically modulate blood–brain barrier function. Biomed Microdevices. 2013;15:145–50.PubMedCrossRef
204.
Walter FR, Valkai S, Kincses A, Petneházi A, Czeller T, Veszelka S, et al. A versatile lab-on-a-chip tool for modeling biological barriers. Sens Actuators B. 2016;222:1209–19.CrossRef
205.
Cho H, Seo JH, Wong KH, Terasaki Y, Park J, Bong K, et al. Three-dimensional blood–brain barrier model for in vitro studies of neurovascular pathology. Sci Rep. 2015;5:15222.PubMedPubMedCentralCrossRef
Metadata
Title
Brain vascular heterogeneity: implications for disease pathogenesis and design of in vitro blood–brain barrier models
Authors
Midrelle E. Noumbissi
Bianca Galasso
Monique F. Stins
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2018
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-018-0097-2

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