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Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Review Article

Current Status of In vitro Models of the Blood-brain Barrier

Author(s): Brijesh Shah and Xiaowei Dong*

Volume 19, Issue 10, 2022

Published on: 12 May, 2022

Page: [1034 - 1046] Pages: 13

DOI: 10.2174/1567201819666220303102614

Price: $65

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Abstract

Disorders of the brain constitute the most debilitating situation globally with increased mortality rates every year, while brain physiology and cumbersome drug development processes exacerbate this. Although blood-brain barrier (BBB) and its components are important for brain protection, their complexity creates major obstacles for brain drug delivery, and the BBB is the primary cause of treatment failure, leading to disease progression. Therefore, developing an ideal platform that can predict the behavior of a drug delivery system in the brain at the early development phase is extremely crucial. In this direction, in the last two decades, numerous in vitro BBB models have been developed and investigated by researchers to understand the barrier properties and how closely the in vitro models mimic in vivo BBB. In-vitro BBB models mainly involve the culture of endothelial cells or their coculture with other perivascular cells either in two or three-dimensional platforms. In this article, we have briefly summarized the fundamentals of BBB and outlined different types of in vitro BBB models with their pros and cons. Based on the available reports, no model seems to be robust that can truly mimic the entire properties of the in vivo BBB microvasculature. However, human stem cells, coculture and threedimensional models have been found to mimic the complexity of the barrier integrity not completely but more precisely than other in vitro models. More studies aiming towards combining these models together would be needed to develop an ideal in vitro model that can overcome the existing limitations and unravel the mysterious BBB vasculature.

Keywords: Blood-brain barrier, in vitro models, tight junctions, endothelial cells, stem cells, perivascular cells.

Graphical Abstract
[1]
Wilhelm, I.; Fazakas, C.; Krizbai, I.A. In vitro models of the blood-brain barrier. Acta Neurobiol. Exp. (Warsz.), 2011, 71(1), 113-128.
[PMID: 21499332]
[2]
Pardridge, W.M. Blood-brain barrier delivery. Drug Discov. Today, 2007, 12(1-2), 54-61.
[http://dx.doi.org/10.1016/j.drudis.2006.10.013] [PMID: 17198973]
[3]
Jamieson, J.J.; Searson, P.C.; Gerecht, S. Engineering the human blood-brain barrier in vitro. J. Biol. Eng., 2017, 11(1), 37.
[http://dx.doi.org/10.1186/s13036-017-0076-1] [PMID: 29213304]
[4]
Wilhelm, I.; Krizbai, I.A. In vitro models of the blood-brain barrier for the study of drug delivery to the brain. Mol. Pharm., 2014, 11(7), 1949-1963.
[http://dx.doi.org/10.1021/mp500046f] [PMID: 24641309]
[5]
Aday, S.; Cecchelli, R.; Hallier-Vanuxeem, D.; Dehouck, M.P.; Ferreira, L. Stem cell-based human blood-brain barrier models for drug discovery and delivery. Trends Biotechnol., 2016, 34(5), 382-393.
[http://dx.doi.org/10.1016/j.tibtech.2016.01.001] [PMID: 26838094]
[6]
Bagchi, S.; Chhibber, T.; Lahooti, B.; Verma, A.; Borse, V.; Jayant, R.D. In-vitro blood-brain barrier models for drug screening and permeation studies: An overview. Drug Des. Devel. Ther., 2019, 13, 3591-3605.
[http://dx.doi.org/10.2147/DDDT.S218708] [PMID: 31695329]
[7]
Appelt-Menzel, A.; Cubukova, A.; Günther, K.; Edenhofer, F.; Piontek, J.; Krause, G.; Stüber, T.; Walles, H.; Neuhaus, W.; Metzger, M. Establishment of a human blood-brain barrier co-culture model mimicking the neurovascular unit using induced pluri- and multipotent stem cells. Stem Cell Reports, 2017, 8(4), 894-906.
[http://dx.doi.org/10.1016/j.stemcr.2017.02.021] [PMID: 28344002]
[8]
Crone, C.; Christensen, O. Electrical resistance of a capillary endothelium. J. Gen. Physiol., 1981, 77(4), 349-371.
[http://dx.doi.org/10.1085/jgp.77.4.349] [PMID: 7241087]
[9]
Olesen, S.P.; Crone, C. Electrical resistance of muscle capillary endothelium. Biophys. J., 1983, 42(1), 31-41.
[http://dx.doi.org/10.1016/S0006-3495(83)84366-5] [PMID: 6601500]
[10]
Wolff, A.; Antfolk, M.; Brodin, B.; Tenje, M. In vitro blood-brain barrier models-an overview of established models and new microfluidic approaches. J. Pharm. Sci., 2015, 104(9), 2727-2746.
[http://dx.doi.org/10.1002/jps.24329] [PMID: 25630899]
[11]
Dong, X. Current strategies for brain drug delivery. Theranostics, 2018, 8(6), 1481-1493.
[http://dx.doi.org/10.7150/thno.21254] [PMID: 29556336]
[12]
Weksler, B.B.; Subileau, E.A.; Perrière, N.; Charneau, P.; Holloway, K.; Leveque, M.; Tricoire-Leignel, H.; Nicotra, A.; Bourdoulous, S.; Turowski, P.; Male, D.K.; Roux, F.; Greenwood, J.; Romero, I.A.; Couraud, P.O. Blood-brain barrier-specific properties of a human adult brain endothelial cell line. FASEB J., 2005, 19(13), 1872-1874.
[http://dx.doi.org/10.1096/fj.04-3458fje] [PMID: 16141364]
[13]
Myers, J.S.; Hare, J.; Sang, Q.A. A simple adaptable blood-brain barrier cell model for screening matrix metalloproteinase inhibitor functionality. Methods Mol. Biol., 2017, 1579, 287-296.
[http://dx.doi.org/10.1007/978-1-4939-6863-3_16] [PMID: 28299744]
[14]
Czupalla, C.J.; Liebner, S.; Devraj, K. In vitro models of the blood-brain barrier. Methods Mol. Biol., 2014, 1135, 415-437.
[http://dx.doi.org/10.1007/978-1-4939-0320-7_34] [PMID: 24510883]
[15]
Dehouck, M.P.; Jolliet-Riant, P.; Brée, F.; Fruchart, J.C.; Cecchelli, R.; Tillement, J.P. Drug transfer across the blood-brain barrier: Correlation between in vitro and in vivo models. J. Neurochem., 1992, 58(5), 1790-1797.
[http://dx.doi.org/10.1111/j.1471-4159.1992.tb10055.x] [PMID: 1560234]
[16]
Andjelkovic, A.V.; Stamatovic, S.M.; Phillips, C.M.; Martinez-Revollar, G.; Keep, R.F. Modeling blood-brain barrier pathology in cerebrovascular disease in vitro: current and future paradigms. Fluids Barriers CNS, 2020, 17(1), 44.
[http://dx.doi.org/10.1186/s12987-020-00202-7] [PMID: 32677965]
[17]
Sivandzade, F.; Cucullo, L. In-vitro blood-brain barrier modeling: A review of modern and fast-advancing technologies. J. Cereb. Blood Flow Metab., 2018, 38(10), 1667-1681.
[http://dx.doi.org/10.1177/0271678X18788769] [PMID: 30058456]
[18]
Bagchi, S.; Lahooti, B.; Chhibber, T.; Varahachalam, S.P.; Mittal, R.; Joshi, A.; Jayant, R.D. In vitro models of central nervous system barriers for blood-brain barrier permeation studies. In: Nanomedicines for Brain Drug Delivery; Morales, J.O.; Gaillard, P.J., Eds.; Humana: New York, 2020; Vol. 157, pp. 235-253.
[http://dx.doi.org/10.1007/978-1-0716-0838-8_9]
[19]
Hartmann, C.; Zozulya, A.; Wegener, J.; Galla, H.J. The impact of glia-derived extracellular matrices on the barrier function of cerebral endothelial cells: An in vitro study. Exp. Cell Res., 2007, 313(7), 1318-1325.
[http://dx.doi.org/10.1016/j.yexcr.2007.01.024] [PMID: 17346702]
[20]
Helms, H.C.; Abbott, N.J.; Burek, M.; Cecchelli, R.; Couraud, P.O.; Deli, M.A.; Förster, C.; Galla, H.J.; Romero, I.A.; Shusta, E.V.; Stebbins, M.J.; Vandenhaute, E.; Weksler, B.; Brodin, B. 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(5), 862-890.
[http://dx.doi.org/10.1177/0271678X16630991] [PMID: 26868179]
[21]
DeBault, L.E.; Cancilla, P.A. Gamma-Glutamyl transpeptidase in isolated brain endothelial cells: Induction by glial cells in vitro. Science, 1980, 207(4431), 653-655.
[http://dx.doi.org/10.1126/science.6101511] [PMID: 6101511]
[22]
Gaillard, P.J.; Voorwinden, L.H.; Nielsen, J.L.; Ivanov, A.; Atsumi, R.; Engman, H.; Ringbom, C.; de Boer, A.G.; Breimer, D.D. 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(3), 215-222.
[http://dx.doi.org/10.1016/S0928-0987(00)00123-8] [PMID: 11113640]
[23]
Jeliazkova-Mecheva, V.V.; Bobilya, D.J. A porcine astrocyte/endothelial cell co-culture model of the blood-brain barrier. Brain Res. Brain Res. Protoc., 2003, 12(2), 91-98.
[http://dx.doi.org/10.1016/j.brainresprot.2003.08.004] [PMID: 14613810]
[24]
Nakagawa, S.; Deli, M.A.; Nakao, S.; Honda, M.; Hayashi, K.; Nakaoke, R.; Kataoka, Y.; Niwa, M. Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells. Cell. Mol. Neurobiol., 2007, 27(6), 687-694.
[http://dx.doi.org/10.1007/s10571-007-9195-4] [PMID: 17823866]
[25]
Dohgu, S.; Takata, F.; Yamauchi, A.; Nakagawa, S.; Egawa, T.; Naito, M.; Tsuruo, T.; Sawada, Y.; Niwa, M.; Kataoka, Y. Brain pericytes contribute to the induction and up-regulation of blood-brain barrier functions through transforming growth factor-beta production. Brain Res., 2005, 1038(2), 208-215.
[http://dx.doi.org/10.1016/j.brainres.2005.01.027] [PMID: 15757636]
[26]
Nakagawa, S.; Deli, M.A.; Kawaguchi, H.; Shimizudani, T.; Shimono, T.; Kittel, A.; Tanaka, K.; Niwa, M. A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes. Neurochem. Int., 2009, 54(3-4), 253-263.
[http://dx.doi.org/10.1016/j.neuint.2008.12.002] [PMID: 19111869]
[27]
Canfield, S.G.; Stebbins, M.J.; Morales, B.S.; Asai, S.W.; Vatine, G.D.; Svendsen, C.N.; Palecek, S.P.; Shusta, E.V. An isogenic blood-brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells. J. Neurochem., 2017, 140(6), 874-888.
[http://dx.doi.org/10.1111/jnc.13923] [PMID: 27935037]
[28]
Yamamizu, K.; Iwasaki, M.; Takakubo, H.; Sakamoto, T.; Ikuno, T.; Miyoshi, M.; Kondo, T.; Nakao, Y.; Nakagawa, M.; Inoue, H.; Yamashita, J.K. In vitro modeling of blood-brain barrier with human iPSC-derived endothelial cells, pericytes, neurons, and astrocytes via notch signaling. Stem Cell Reports, 2017, 8(3), 634-647.
[http://dx.doi.org/10.1016/j.stemcr.2017.01.023] [PMID: 28238797]
[29]
Mantle, J.L.; Min, L.; Lee, K.H. Minimum transendothelial electrical resistance thresholds for the study of small and large molecule drug transport in a human in vitro blood-brain barrier model. Mol. Pharm., 2016, 13(12), 4191-4198.
[http://dx.doi.org/10.1021/acs.molpharmaceut.6b00818] [PMID: 27934481]
[30]
Kokubu, Y.; Yamaguchi, T.; Kawabata, K. In vitro model of cerebral ischemia by using brain microvascular endothelial cells derived from human induced pluripotent stem cells. Biochem. Biophys. Res. Commun., 2017, 486(2), 577-583.
[http://dx.doi.org/10.1016/j.bbrc.2017.03.092] [PMID: 28336435]
[31]
Adriani, G.; Ma, D.; Pavesi, A.; Kamm, R.D.; Goh, E.L. A 3D neurovascular microfluidic model consisting of neurons, astrocytes and cerebral endothelial cells as a blood-brain barrier. Lab Chip, 2017, 17(3), 448-459.
[http://dx.doi.org/10.1039/C6LC00638H] [PMID: 28001148]
[32]
Crisan, M.; Yap, S.; Casteilla, L.; Chen, C.W.; Corselli, M.; Park, T.S.; Andriolo, G.; Sun, B.; Zheng, B.; Zhang, L.; Norotte, C.; Teng, P.N.; Traas, J.; Schugar, R.; Deasy, B.M.; Badylak, S.; Buhring, H.J.; Giacobino, J.P.; Lazzari, L.; Huard, J.; Péault, B. A perivascular origin for mesenchymal stem cells in multiple human organs. Cell Stem Cell, 2008, 3(3), 301-313.
[http://dx.doi.org/10.1016/j.stem.2008.07.003] [PMID: 18786417]
[33]
Tian, X.; Brookes, O.; Battaglia, G. Pericytes from mesenchymal stem cells as a model for the blood-brain barrier. Sci. Rep., 2017, 7(1), 39676.
[http://dx.doi.org/10.1038/srep39676] [PMID: 28098158]
[34]
Cucullo, L.; Couraud, P.O.; Weksler, B.; Romero, I.A.; Hossain, M.; Rapp, E.; Janigro, D. Immortalized human brain endothelial cells and flow-based vascular modeling: A marriage of convenience for rational neurovascular studies. J. Cereb. Blood Flow Metab., 2008, 28(2), 312-328.
[http://dx.doi.org/10.1038/sj.jcbfm.9600525] [PMID: 17609686]
[35]
Cucullo, L.; Marchi, N.; Hossain, M.; Janigro, D. A dynamic in vitro BBB model for the study of immune cell trafficking into the central nervous system. J. Cereb. Blood Flow Metab., 2011, 31(2), 767-777.
[http://dx.doi.org/10.1038/jcbfm.2010.162] [PMID: 20842162]
[36]
Siddharthan, V.; Kim, Y.V.; Liu, S.; Kim, K.S. Human astrocytes/astrocyte-conditioned medium and shear stress enhance the barrier properties of human brain microvascular endothelial cells. Brain Res., 2007, 1147, 39-50.
[http://dx.doi.org/10.1016/j.brainres.2007.02.029] [PMID: 17368578]
[37]
Prabhakarpandian, B.; Shen, M.C.; Nichols, J.B.; Mills, I.R.; Sidoryk-Wegrzynowicz, M.; Aschner, M.; Pant, K. SyM-BBB: A microfluidic blood brain barrier model. Lab Chip, 2013, 13(6), 1093-1101.
[http://dx.doi.org/10.1039/c2lc41208j] [PMID: 23344641]
[38]
Deosarkar, S.P.; Prabhakarpandian, B.; Wang, B.; Sheffield, J.B.; Krynska, B.; Kiani, M.F. A novel dynamic neonatal blood-brain barrier on a chip. PLoS One, 2015, 10(11), e0142725.
[http://dx.doi.org/10.1371/journal.pone.0142725] [PMID: 26555149]
[39]
Yeon, J.H.; Na, D.; Choi, K.; Ryu, S.W.; Choi, C.; Park, J.K. Reliable permeability assay system in a microfluidic device mimicking cerebral vasculatures. Biomed. Microdevices, 2012, 14(6), 1141-1148.
[http://dx.doi.org/10.1007/s10544-012-9680-5] [PMID: 22821236]
[40]
Oddo, A.; Peng, B.; Tong, Z.; Wei, Y.; Tong, W.Y.; Thissen, H.; Voelcker, N.H. Advances in microfluidic Blood-Brain Barrier (BBB) models. Trends Biotechnol., 2019, 37(12), 1295-1314.
[http://dx.doi.org/10.1016/j.tibtech.2019.04.006] [PMID: 31130308]
[41]
Jiang, L.; Li, S.; Zheng, J.; Li, Y.; Huang, H. Recent progress in microfluidic models of the blood-brain barrier. Micromachines (Basel), 2019, 10(6), E375.
[http://dx.doi.org/10.3390/mi10060375] [PMID: 31195652]
[42]
Menon, N.V.; Chuah, Y.J.; Cao, B.; Lim, M.; Kang, Y. A microfluidic co-culture system to monitor tumor-stromal interactions on a chip. Biomicrofluidics, 2014, 8(6), 064118.
[http://dx.doi.org/10.1063/1.4903762] [PMID: 25553194]
[43]
Kim, J.A.; Kim, H.N.; Im, S.K.; Chung, S.; Kang, J.Y.; Choi, N. Collagen-based brain microvasculature model in vitro using three-dimensional printed template. Biomicrofluidics, 2015, 9(2), 024115.
[http://dx.doi.org/10.1063/1.4917508] [PMID: 25945141]
[44]
Griep, L.M.; Wolbers, F.; de Wagenaar, B.; ter Braak, P.M.; Weksler, B.B.; Romero, I.A.; Couraud, P.O.; Vermes, I.; van der Meer, A.D.; van den Berg, A. BBB on chip: microfluidic platform to mechanically and biochemically modulate blood-brain barrier function. Biomed. Microdevices, 2013, 15(1), 145-150.
[http://dx.doi.org/10.1007/s10544-012-9699-7] [PMID: 22955726]
[45]
Modarres, H.P.; Janmaleki, M.; Novin, M.; Saliba, J.; El-Hajj, F. RezayatiCharan, M.; Seyfoori, A.; Sadabadi, H.; Vandal, M.; Nguyen, M.D.; Hasan, A.; Sanati-Nezhad, A. In vitro models and systems for evaluating the dynamics of drug delivery to the healthy and diseased brain. J. Control. Release, 2018, 273, 108-130.
[http://dx.doi.org/10.1016/j.jconrel.2018.01.024] [PMID: 29378233]
[46]
Bhalerao, A.; Sivandzade, F.; Archie, S.R.; Chowdhury, E.A.; Noorani, B.; Cucullo, L. In vitro modeling of the neurovascular unit: Advances in the field. Fluids Barriers CNS, 2020, 17(1), 22.
[http://dx.doi.org/10.1186/s12987-020-00183-7] [PMID: 32178700]
[47]
Park, T.E.; Mustafaoglu, N.; Herland, A.; Hasselkus, R.; Mannix, R.; FitzGerald, E.A.; Prantil-Baun, R.; Watters, A.; Henry, O.; Benz, M.; Sanchez, H.; McCrea, H.J.; Goumnerova, L.C.; Song, H.W.; Palecek, S.P.; Shusta, E.; Ingber, D.E. Hypoxia-enhanced blood-brain barrier Chip recapitulates human barrier function and shuttling of drugs and antibodies. Nat. Commun., 2019, 10(1), 2621.
[http://dx.doi.org/10.1038/s41467-019-10588-0] [PMID: 31197168]
[48]
Shi, L.; Zeng, M.; Sun, Y.; Fu, B.M. Quantification of blood-brain barrier solute permeability and brain transport by multiphoton microscopy. J. Biomech. Eng., 2014, 136(3), 031005.
[http://dx.doi.org/10.1115/1.4025892] [PMID: 24193698]
[49]
Shayan, G.; Choi, Y.S.; Shusta, E.V.; Shuler, M.L.; Lee, K.H. Murine in vitro model of the blood-brain barrier for evaluating drug transport. Eur. J. Pharm. Sci., 2011, 42(1-2), 148-155.
[http://dx.doi.org/10.1016/j.ejps.2010.11.005] [PMID: 21078386]
[50]
Silwedel, C.; Förster, C. Differential susceptibility of cerebral and cerebellar murine brain microvascular endothelial cells to loss of barrier properties in response to inflammatory stimuli. J. Neuroimmunol., 2006, 179(1-2), 37-45.
[http://dx.doi.org/10.1016/j.jneuroim.2006.06.019] [PMID: 16884785]
[51]
Abbott, N.J.; Dolman, D.E.; Drndarski, S.; Fredriksson, S.M. An improved in vitro blood-brain barrier model: Rat brain endothelial cells co-cultured with astrocytes. In: Methods in Molecular Biology (Methods and Protocols); Milner, R., Ed.; Humana Press, 2011; 814, p. 415, 430.
[52]
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(1-3), 77-83.
[http://dx.doi.org/10.1016/j.regpep.2004.05.023] [PMID: 15518896]
[53]
Thomsen, L.B.; Burkhart, A.; Moos, T. A triple culture model of the blood-brain barrier using porcine brain endothelial cells, astrocytes and pericytes. PLoS One, 2015, 10(8), e0134765.
[http://dx.doi.org/10.1371/journal.pone.0134765] [PMID: 26241648]
[54]
Hatherell, K.; Couraud, P.O.; Romero, I.A.; Weksler, B.; Pilkington, G.J. 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(2), 223-229.
[http://dx.doi.org/10.1016/j.jneumeth.2011.05.012] [PMID: 21609734]
[55]
Cucullo, L.; McAllister, M.S.; Kight, K.; Krizanac-Bengez, L.; Marroni, M.; Mayberg, M.R.; Stanness, K.A.; Janigro, D. A new dynamic in vitro model for the multidimensional study of astrocyte-endothelial cell interactions at the blood-brain barrier. Brain Res., 2002, 951(2), 243-254.
[http://dx.doi.org/10.1016/S0006-8993(02)03167-0] [PMID: 12270503]
[56]
Cucullo, L.; Hossain, M.; Tierney, W.; Janigro, D. A new dynamic in vitro modular capillaries-venules modular system: Cerebrovascular physiology in a box. BMC Neurosci., 2013, 14(1), 18.
[http://dx.doi.org/10.1186/1471-2202-14-18] [PMID: 23388041]
[57]
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(1), 40.
[http://dx.doi.org/10.1186/1471-2202-12-40] [PMID: 21569296]
[58]
Booth, R.; Kim, H. Characterization of a microfluidic in vitro model of the blood-brain barrier (μBBB). Lab Chip, 2012, 12(10), 1784-1792.
[http://dx.doi.org/10.1039/c2lc40094d] [PMID: 22422217]
[59]
Wang, Y.I.; Abaci, H.E.; Shuler, M.L. Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol. Bioeng., 2017, 114(1), 184-194.
[http://dx.doi.org/10.1002/bit.26045] [PMID: 27399645]
[60]
Brown, J.A.; Pensabene, V.; Markov, D.A.; Allwardt, V.; Neely, M.D.; Shi, M.; Britt, C.M.; Hoilett, O.S.; Yang, Q.; Brewer, B.M.; Samson, P.C.; McCawley, L.J.; May, J.M.; Webb, D.J.; Li, D.; Bowman, A.B.; Reiserer, R.S.; Wikswo, J.P. Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor. Biomicrofluidics, 2015, 9(5), 054124.
[http://dx.doi.org/10.1063/1.4934713] [PMID: 26576206]
[61]
Herland, A.; van der Meer, A.D.; FitzGerald, E.A.; Park, T.E.; Sleeboom, J.J.; Ingber, D.E. Distinct contributions of astrocytes and pericytes to neuroinflammation identified in a 3D human blood-brain barrier on a chip. PLoS One, 2016, 11(3), e0150360.
[http://dx.doi.org/10.1371/journal.pone.0150360] [PMID: 26930059]
[62]
Tornabene, E.; Brodin, B. Stroke and drug delivery-in vitro models of the ischemic blood-brain barrier. J. Pharm. Sci., 2016, 105(2), 398-405.
[http://dx.doi.org/10.1016/j.xphs.2015.11.041] [PMID: 26869407]
[63]
Komarova, Y.A.; Kruse, K.; Mehta, D.; Malik, A.B. Protein interactions at endothelial junctions and signaling mechanisms regulating endothelial permeability. Circ. Res., 2017, 120(1), 179-206.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.306534] [PMID: 28057793]

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