In Vitro Blood-Brain Barrier Models for Neuroinfectious Diseases: A Narrative Review


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Abstract

The blood-brain barrier (BBB) is a complex, dynamic, and adaptable barrier between the peripheral blood system and the central nervous system. While this barrier protects the brain and spinal cord from inflammation and infection, it prevents most drugs from reaching the brain tissue. With the expanding interest in the pathophysiology of BBB, the development of in vitro BBB models has dramatically evolved. However, due to the lack of a standard model, a range of experimental protocols, BBB-phenotype markers, and permeability flux markers was utilized to construct in vitro BBB models. Several neuroinfectious diseases are associated with BBB dysfunction. To conduct neuroinfectious disease research effectively, there stems a need to design representative in vitro human BBB models that mimic the BBB's functional and molecular properties. The highest necessity is for an in vitro standardised BBB model that accurately represents all the complexities of an intact brain barrier. Thus, this in-depth review aims to describe the optimization and validation parameters for building BBB models and to discuss previous research on neuroinfectious diseases that have utilized in vitro BBB models. The findings in this review may serve as a basis for more efficient optimisation, validation, and maintenance of a structurally- and functionally intact BBB model, particularly for future studies on neuroinfectious diseases.

About the authors

Ahmad Badawi

Department of Neurology, Faculty of Medicine and Health Sciences,, Universiti Putra Malaysia

Email: info@benthamscience.net

Nur Mohamad

Department of Neurology, Faculty of Medicine and Health Sciences,, Universiti Putra Malaysia

Email: info@benthamscience.net

Johnson Stanslas

Department of Medicine, Faculty of Medicine and Health Sciences,, Universiti Putra Malaysia

Email: info@benthamscience.net

Brian Kirby

School of Pharmacy and Biomolecular Sciences,, RCSI University of Medicine and Health Sciences

Email: info@benthamscience.net

Vasantha Neela

Department of Medical Microbiology and Parasitology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia

Email: info@benthamscience.net

Rajesh Ramasamy

Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia

Email: info@benthamscience.net

Hamidon Basri

Department of Neurology, Faculty of Medicine and Health Sciences,, Universiti Putra Malaysia

Author for correspondence.
Email: info@benthamscience.net

References

  1. Abbott, N.J. Future perspectives. In: Blood-brain barrier in drug discovery: optimizing brain exposure of cns drugs and minimizing brain side effects for peripheral drugs; Di, L.; Kerns, E.H., Eds.; Wiley, 2015; pp. 1-586. doi: 10.1002/9781118788523.ch26
  2. Burkhart, A.; Thomsen, L.B.; Thomsen, M.S.; Lichota, J.; Fazakas, C.; Krizbai, I.; Moos, T. Transfection of brain capillary endothelial cells in primary culture with defined blood-brain barrier properties. Fluids Barriers CNS, 2015, 12(1), 19. doi: 10.1186/s12987-015-0015-9 PMID: 26246240
  3. Kim, K.S. Pathogenesis of bacterial meningitis: From bacteraemia to neuronal injury. Nat. Rev. Neurosci., 2003, 4(5), 376-385. doi: 10.1038/nrn1103 PMID: 12728265
  4. Kim, K.S. Mechanisms of microbial traversal of the blood-brain barrier. Nat. Rev. Microbiol., 2008, 6(8), 625-634. doi: 10.1038/nrmicro1952 PMID: 18604221
  5. Candelario-Jalil, E.; Yang, Y.; Rosenberg, G.A. Diverse roles of matrix metalloproteinases and tissue inhibitors of metalloproteinases in neuroinflammation and cerebral ischemia. Neuroscience, 2009, 158(3), 983-994. doi: 10.1016/j.neuroscience.2008.06.025 PMID: 18621108
  6. Verma, S.; Kumar, M.; Gurjav, U.; Lum, S.; Nerurkar, V.R. Reversal of West Nile virus-induced blood-brain barrier disruption and tight junction proteins degradation by matrix metalloproteinases inhibitor. Virology, 2010, 397(1), 130-138. doi: 10.1016/j.virol.2009.10.036 PMID: 19922973
  7. Roberts, T.K.; Buckner, C.M.; Berman, J.W. Leukocyte transmigration across the blood-brain barrier: Perspectives on neuroAIDS. Front. Biosci., 2010, 15(1), 478-536. doi: 10.2741/3631 PMID: 20036831
  8. Greenwood, J.; Heasman, S.J.; Alvarez, J.I.; Prat, A.; Lyck, R.; Engelhardt, B. Review: Leucocyte-endothelial cell crosstalk at the blood-brain barrier: A prerequisite for successful immune cell entry to the brain. Neuropathol. Appl. Neurobiol., 2011, 37(1), 24-39. doi: 10.1111/j.1365-2990.2010.01140.x PMID: 20946472
  9. Winger, R.C.; Koblinski, J.E.; Kanda, T.; Ransohoff, R.M.; Muller, W.A. Rapid remodeling of tight junctions during paracellular diapedesis in a human model of the blood-brain barrier. J. Immunol., 2014, 193(5), 2427-2437. doi: 10.4049/jimmunol.1400700 PMID: 25063869
  10. Varatharajan, L.; Thomas, S.A. The transport of anti-HIV drugs across blood-CNS interfaces: Summary of current knowledge and recommendations for further research. Antiviral Res., 2009, 82(2), A99-A109. doi: 10.1016/j.antiviral.2008.12.013 PMID: 19176219
  11. Deli, M.A.; Ábrahám, C.S.; Kataoka, Y.; Niwa, M. Permeability studies on in vitro blood-brain barrier models: physiology, pathology, and pharmacology. Cell. Mol. Neurobiol., 2005, 25(1), 59-127. doi: 10.1007/s10571-004-1377-8 PMID: 15962509
  12. Patabendige, A. The value of in vitro models of the blood-brain barrier and their uses. Altern. Lab. Anim., 2012, 40(6), 335-338. doi: 10.1177/026119291204000606 PMID: 23398338
  13. Patabendige, A.; Michael, B.D.; Craig, A.G.; Solomon, T. Brain microvascular endothelial-astrocyte cell responses following Japanese encephalitis virus infection in an in vitro human blood-brain barrier model. Mol. Cell. Neurosci., 2018, 89, 60-70. doi: 10.1016/j.mcn.2018.04.002 PMID: 29635016
  14. Abbott, N.J. Astrocyte-endothelial interactions and blood-brain barrier permeability. J. Anat., 2002, 200(6), 629-638. doi: 10.1046/j.1469-7580.2002.00064.x PMID: 12162730
  15. Sims, D.E. Diversity within pericytes. Clin. Exp. Pharmacol. Physiol., 2000, 27(10), 842-846. doi: 10.1046/j.1440-1681.2000.03343.x PMID: 11022980
  16. Abbott, N.J.; Rönnbäck, L.; Hansson, E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci., 2006, 7(1), 41-53. doi: 10.1038/nrn1824 PMID: 16371949
  17. 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-β production. Brain Res., 2005, 1038(2), 208-215. doi: 10.1016/j.brainres.2005.01.027 PMID: 15757636
  18. Hawkins, B.T.; Davis, T.P. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol. Rev., 2005, 57(2), 173-185. doi: 10.1124/pr.57.2.4 PMID: 15914466
  19. Chaudhuri, J.D. Blood brain barrier and infection. Med. Sci. Monit., 2000, 6(6), 1213-1222. PMID: 11208482
  20. de Boer, A.G.; Gaillard, P.J. Drug targeting to the brain. Annu. Rev. Pharmacol. Toxicol., 2007, 47(1), 323-355. doi: 10.1146/annurev.pharmtox.47.120505.105237 PMID: 16961459
  21. Harhaj, N.S.; Antonetti, D.A. Regulation of tight junctions and loss of barrier function in pathophysiology. Int. J. Biochem. Cell Biol., 2004, 36(7), 1206-1237. doi: 10.1016/j.biocel.2003.08.007 PMID: 15109567
  22. Kniesel, U.; Wolburg, H. Tight junctions of the blood-brain barrier. Cell. Mol. Neurobiol., 2000, 20(1), 57-76. doi: 10.1023/A:1006995910836 PMID: 10690502
  23. Schulze, C.; Firth, J.A. Immunohistochemical localization of adherens junction components in blood-brain barrier microvessels of the rat. J. Cell Sci., 1993, 104(3), 773-782. doi: 10.1242/jcs.104.3.773 PMID: 8314872
  24. Vorbrodt, A.W.; Dobrogowska, D.H. Molecular anatomy of interendothelial junctions in human blood-brain barrier microvessels. Folia Histochem. Cytobiol., 2004, 42(2), 67-75. PMID: 15253128
  25. Wolburg, H.; Lippoldt, A. Tight junctions of the blood-brain barrier. Vascul. Pharmacol., 2002, 38(6), 323-337. doi: 10.1016/S1537-1891(02)00200-8 PMID: 12529927
  26. Bagley, R.G.; Weber, W.; Rouleau, C.; Teicher, B.A. Pericytes and endothelial precursor cells: Cellular interactions and contributions to malignancy. Cancer Res., 2005, 65(21), 9741-9750. doi: 10.1158/0008-5472.CAN-04-4337 PMID: 16266995
  27. Dore-Duffy, P. Pericytes: Pluripotent cells of the blood brain barrier. Curr. Pharm. Des., 2008, 14(16), 1581-1593. doi: 10.2174/138161208784705469 PMID: 18673199
  28. Winkler, E.A.; Bell, R.D.; Zlokovic, B.V. Central nervous system pericytes in health and disease. Nat. Neurosci., 2011, 14(11), 1398-1405. doi: 10.1038/nn.2946 PMID: 22030551
  29. Hori, S.; Ohtsuki, S.; Hosoya, K.; Nakashima, E.; Terasaki, T. A pericyte‐derived angiopoietin‐1 multimeric complex induces occludin gene expression in brain capillary endothelial cells through Tie‐2 activation in vitro. J. Neurochem., 2004, 89(2), 503-513. doi: 10.1111/j.1471-4159.2004.02343.x PMID: 15056293
  30. Levéen, P.; Pekny, M.; Gebre-Medhin, S.; Swolin, B.; Larsson, E.; Betsholtz, C. Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities. Genes Dev., 1994, 8(16), 1875-1887. doi: 10.1101/gad.8.16.1875 PMID: 7958863
  31. Lindahl, P.; Johansson, B.R.; Levéen, P.; Betsholtz, C. Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science (80-), 1997, 277(5323), 242-245.
  32. Igarashi, Y.; Utsumi, H.; Chiba, H.; Yamada-Sasamori, Y.; Tobioka, H.; Kamimura, Y.; Furuuchi, K.; Kokai, Y.; Nakagawa, T.; Mori, M.; Sawada, N. Glial cell line-derived neurotrophic factor induces barrier function of endothelial cells forming the blood-brain barrier. Biochem. Biophys. Res. Commun., 1999, 261(1), 108-112. doi: 10.1006/bbrc.1999.0992 PMID: 10405331
  33. Ifergan, I.; Kebir, H.; Terouz, S.; Alvarez, J.I.; Lécuyer, M.A.; Gendron, S.; Bourbonnière, L.; Dunay, I.R.; Bouthillier, A.; Moumdjian, R.; Fontana, A.; Haqqani, A.; Klopstein, A.; Prinz, M.; López-Vales, R.; Birchler, T.; Prat, A. Role of ninjurin‐1 in the migration of myeloid cells to central nervous system inflammatory lesions. Ann. Neurol., 2011, 70(5), 751-763. doi: 10.1002/ana.22519 PMID: 22162058
  34. Alvarez, JI; Dodelet-Devillers, A; Kebir, H; Ifergan, I; Fabre, PJ; Terouz, S The hedgehog pathway promotes blood-brain barrier integrity and CNS immune quiescence. Science (80-), 2011, 334(6063), 1727-1731. doi: 10.1126/science.1206936
  35. Schlageter, K.E.; Molnar, P.; Lapin, G.D.; Groothuis, D.R. Microvessel organization and structure in experimental brain tumors: microvessel populations with distinctive structural and functional properties. Microvasc. Res., 1999, 58(3), 312-328. doi: 10.1006/mvre.1999.2188 PMID: 10527772
  36. Hellström, M.; Gerhardt, H.; Kalén, M.; Li, X.; Eriksson, U.; Wolburg, H.; Betsholtz, C. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J. Cell Biol., 2001, 153(3), 543-554. doi: 10.1083/jcb.153.3.543 PMID: 11331305
  37. Kacem, K.; Lacombe, P.; Seylaz, J.; Bonvento, G. Structural organization of the perivascular astrocyte endfeet and their relationship with the endothelial glucose transporter: A confocal microscopy study. Glia, 1998, 23(1), 1-10. doi: 10.1002/(SICI)1098-1136(199805)23:13.0.CO;2-B PMID: 9562180
  38. Zlokovic, B.V. The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron, 2008, 57(2), 178-201. doi: 10.1016/j.neuron.2008.01.003 PMID: 18215617
  39. Man, S.; Ubogu, E.E.; Ransohoff, R.M. Inflammatory cell migration into the central nervous system: A few new twists on an old tale. Brain Pathol., 2007, 17(2), 243-250. doi: 10.1111/j.1750-3639.2007.00067.x PMID: 17388955
  40. Tontsch, U.; Bauer, H.C. Glial cells and neurons induce blood-brain barrier related enzymes in cultured cerebral endothelial cells. Brain Res., 1991, 539(2), 247-253. doi: 10.1016/0006-8993(91)91628-E PMID: 1675906
  41. Savettieri, G.; Liegro, I.D.; Catania, C.; Licata, L.; Pitarresi, G.L. DʼAgostino, S.; Schiera, G.; De Caro, V.; Giandalia, G.; Giannola, L.I.; Cestelli, A. Neurons and ECM regulate occludin localization in brain endothelial cells. Neuroreport, 2000, 11(5), 1081-1084. doi: 10.1097/00001756-200004070-00035 PMID: 10790886
  42. Pulido, R.S.; Munji, R.N.; Chan, T.C.; Quirk, C.R.; Weiner, G.A.; Weger, B.D.; Rossi, M.J.; Elmsaouri, S.; Malfavon, M.; Deng, A.; Profaci, C.P.; Blanchette, M.; Qian, T.; Foreman, K.L.; Shusta, E.V.; Gorman, M.R.; Gachon, F.; Leutgeb, S.; Daneman, R. Neuronal activity regulates blood-brain barrier efflux transport through endothelial circadian genes. Neuron, 2020, 108(5), 937-952.e7. doi: 10.1016/j.neuron.2020.09.002 PMID: 32979312
  43. Rhea, E.M.; Banks, W.A. Role of the blood-brain barrier in central nervous system insulin resistance. Front. Neurosci., 2019, 13, 521. doi: 10.3389/fnins.2019.00521 PMID: 31213970
  44. Fabriek, B.O.; Van Haastert, E.S.; Galea, I.; Polfliet, M.M.J.; Döpp, E.D.; Van Den Heuvel, M.M.; Van Den Berg, T.K.; De Groot, C.J.A.; Van Der Valk, P.; Dijkstra, C.D. CD163‐positive perivascular macrophages in the human CNS express molecules for antigen recognition and presentation. Glia, 2005, 51(4), 297-305. doi: 10.1002/glia.20208 PMID: 15846794
  45. Haruwaka, K.; Ikegami, A.; Tachibana, Y.; Ohno, N.; Konishi, H.; Hashimoto, A.; Matsumoto, M.; Kato, D.; Ono, R.; Kiyama, H.; Moorhouse, A.J.; Nabekura, J.; Wake, H. Dual microglia effects on blood brain barrier permeability induced by systemic inflammation. Nat. Commun., 2019, 10(1), 5816. doi: 10.1038/s41467-019-13812-z PMID: 31862977
  46. Joost, E.; Jordão, M.J.C.; Mages, B.; Prinz, M.; Bechmann, I.; Krueger, M. Microglia contribute to the glia limitans around arteries, capillaries and veins under physiological conditions, in a model of neuroinflammation and in human brain tissue. Brain Struct. Funct., 2019, 224(3), 1301-1314. doi: 10.1007/s00429-019-01834-8 PMID: 30706162
  47. Abbott, N.J.; Patabendige, A.A.K.; Dolman, D.E.M.; Yusof, S.R.; Begley, D.J. Structure and function of the blood-brain barrier. Neurobiol. Dis., 2010, 37(1), 13-25. doi: 10.1016/j.nbd.2009.07.030 PMID: 19664713
  48. Stewart, P.A.; Wiley, M.J. Developing nervous tissue induces formation of blood-brain barrier characteristics in invading endothelial cells: A study using quail-chick transplantation chimeras. Dev. Biol., 1981, 84(1), 183-192. doi: 10.1016/0012-1606(81)90382-1 PMID: 7250491
  49. Kadl, A.; Leitinger, N. The role of endothelial cells in the resolution of acute inflammation. Antioxid. Redox Signal., 2005, 7(11-12), 1744-1754. doi: 10.1089/ars.2005.7.1744 PMID: 16356135
  50. Cecchelli, R.; Berezowski, V.; Lundquist, S.; Culot, M.; Renftel, M.; Dehouck, M.P.; Fenart, L. Modelling of the blood-brain barrier in drug discovery and development. Nat. Rev. Drug Discov., 2007, 6(8), 650-661. doi: 10.1038/nrd2368 PMID: 17667956
  51. Emmi, A.; Wenzel, H.J.; Schwartzkroin, P.A.; Taglialatela, M.; Castaldo, P.; Bianchi, L.; Nerbonne, J.; Robertson, G.A.; Janigro, D. Do glia have heart? Expression and functional role for ether-a-go-go currents in hippocampal astrocytes. J. Neurosci., 2000, 20(10), 3915-3925. doi: 10.1523/JNEUROSCI.20-10-03915.2000 PMID: 10804231
  52. Sá-Pereira, I.; Brites, D.; Brito, M.A. Neurovascular unit: A focus on pericytes. Mol. Neurobiol., 2012, 45(2), 327-347. doi: 10.1007/s12035-012-8244-2 PMID: 22371274
  53. Dore-duffy, P.; Cleary, K. Morphology and properties of pericytes. In: The Blood-Brain and Other Neural Barriers Methods in Molecular Biology (Methods and Protocols); Nag, S., Ed.; Humana Press, 2011. doi: 10.1007/978-1-60761-938-3_2
  54. Armulik, A.; Genové, G.; Betsholtz, C. Pericytes: Developmental, physiological, and pathological perspectives, problems, and promises. Dev. Cell, 2011, 21(2), 193-215. doi: 10.1016/j.devcel.2011.07.001 PMID: 21839917
  55. Sweeney, M.D.; Ayyadurai, S.; Zlokovic, B.V. Pericytes of the neurovascular unit: Key functions and signaling pathways. Nat. Neurosci., 2016, 19(6), 771-783. doi: 10.1038/nn.4288 PMID: 27227366
  56. Armulik, A.; Genové, G.; Mäe, M.; Nisancioglu, M.H.; Wallgard, E.; Niaudet, C.; He, L.; Norlin, J.; Lindblom, P.; Strittmatter, K.; Johansson, B.R.; Betsholtz, C. Pericytes regulate the blood-brain barrier. Nature, 2010, 468(7323), 557-561. doi: 10.1038/nature09522 PMID: 20944627
  57. Ben-Zvi, A.; Lacoste, B.; Kur, E.; Andreone, B.J.; Mayshar, Y.; Yan, H.; Gu, C. Mfsd2a is critical for the formation and function of the blood-brain barrier. Nature, 2014, 509(7501), 507-511. doi: 10.1038/nature13324 PMID: 24828040
  58. Daneman, R.; Zhou, L.; Kebede, A.A.; Barres, B.A. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature, 2010, 468(7323), 562-566. doi: 10.1038/nature09513 PMID: 20944625
  59. Gerhardt, H.; Wolburg, H.; Redies, C. N‐cadherin mediates pericytic‐endothelial interaction during brain angiogenesis in the chicken. Dev. Dyn., 2000, 218(3), 472-479. doi: 10.1002/1097-0177(200007)218:33.0.CO;2-# PMID: 10878612
  60. Allt, G.; Lawrenson, J.G. Pericytes: Cell biology and pathology. Cells Tissues Organs, 2001, 169(1), 1-11. doi: 10.1159/000047855 PMID: 11340256
  61. Aguilera, K.Y.; Brekken, R.A. Recruitment and retention: Factors that affect pericyte migration. Cell. Mol. Life Sci., 2014, 71(2), 299-309. doi: 10.1007/s00018-013-1432-z PMID: 23912898
  62. Bell, R.D.; Winkler, E.A.; Sagare, A.P.; Singh, I.; LaRue, B.; Deane, R.; Zlokovic, B.V. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron, 2010, 68(3), 409-427. doi: 10.1016/j.neuron.2010.09.043 PMID: 21040844
  63. Shepro, D.; Morel, N.M.L. Pericyte physiology. FASEB J., 1993, 7(11), 1031-1038. doi: 10.1096/fasebj.7.11.8370472 PMID: 8370472
  64. Nakagawa, S.; Deli, M.A.; Kawaguchi, H.; Shimizudani, T.; Shimono, T.; Kittel, Á.; 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. doi: 10.1016/j.neuint.2008.12.002 PMID: 19111869
  65. Wang, S.; Cao, C.; Chen, Z.; Bankaitis, V.; Tzima, E.; Sheibani, N.; Burridge, K. Pericytes regulate vascular basement membrane remodeling and govern neutrophil extravasation during inflammation. PLoS One, 2012, 7(9), e45499. doi: 10.1371/journal.pone.0045499 PMID: 23029055
  66. Nichols, N.R.; Day, J.R.; Laping, N.J.; Johnson, S.A.; Finch, C.E. GFAP mRNA increases with age in rat and human brain. Neurobiol. Aging, 1993, 14(5), 421-429. doi: 10.1016/0197-4580(93)90100-P PMID: 8247224
  67. Oberheim, N.A.; Takano, T.; Han, X.; He, W.; Lin, J.H.C.; Wang, F.; Xu, Q.; Wyatt, J.D.; Pilcher, W.; Ojemann, J.G.; Ransom, B.R.; Goldman, S.A.; Nedergaard, M. Uniquely hominid features of adult human astrocytes. J. Neurosci., 2009, 29(10), 3276-3287. doi: 10.1523/JNEUROSCI.4707-08.2009 PMID: 19279265
  68. Bazargani, N.; Attwell, D. Astrocyte calcium signaling: The third wave. Nat. Neurosci., 2016, 19(2), 182-189. doi: 10.1038/nn.4201 PMID: 26814587
  69. Mathiisen, T.M.; Lehre, K.P.; Danbolt, N.C.; Ottersen, O.P. The perivascular astroglial sheath provides a complete covering of the brain microvessels: An electron microscopic 3D reconstruction. Glia, 2010, 58(9), 1094-1103. doi: 10.1002/glia.20990 PMID: 20468051
  70. Gee, J.R.; Keller, J.N. Astrocytes: Regulation of brain homeostasis via apolipoprotein E. Int. J. Biochem. Cell Biol., 2005, 37(6), 1145-1150. doi: 10.1016/j.biocel.2004.10.004 PMID: 15778078
  71. Friede, R. Quantitative share of the glia in development of the cortex. Acta Anat., 1954, 20(3), 290-296. doi: 10.1159/000140905 PMID: 13137775
  72. Pelvig, D.P.; Pakkenberg, H.; Stark, A.K.; Pakkenberg, B. Neocortical glial cell numbers in human brains. Neurobiol. Aging, 2008, 29(11), 1754-1762. doi: 10.1016/j.neurobiolaging.2007.04.013 PMID: 17544173
  73. Herculano-Houzel, S. The glia/neuron ratio: How it varies uniformly across brain structures and species and what that means for brain physiology and evolution. Glia, 2014, 62(9), 1377-1391. doi: 10.1002/glia.22683 PMID: 24807023
  74. Nagy, J.I.; Patel, D.; Ochalski, P.A.Y.; Stelmack, G.L. Connexin30 in rodent, cat and human brain: Selective expression in gray matter astrocytes, co-localization with connexin43 at gap junctions and late developmental appearance. Neuroscience, 1999, 88(2), 447-468. doi: 10.1016/S0306-4522(98)00191-2 PMID: 10197766
  75. 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. doi: 10.1016/S0928-0987(00)00123-8 PMID: 11113640
  76. Yung, W.K.; Luna, M.; Borit, A. Vimentin and glial fibrillary acidic protein in human brain tumors. J. Neurooncol., 1985, 3(1), 35-38. doi: 10.1007/BF00165169 PMID: 3889231
  77. Sun, D.; Lytle, C.; O’Donnell, M.E. IL-6 secreted by astroglial cells regulates Na-K-Cl cotransport in brain microvessel endothelial cells. Am. J. Physiol. Cell Physiol., 1997, 272(6), C1829-C1835. doi: 10.1152/ajpcell.1997.272.6.C1829 PMID: 9227411
  78. Sobue, K.; Yamamoto, N.; Yoneda, K.; Hodgson, M.E.; Yamashiro, K.; Tsuruoka, N.; Tsuda, T.; Katsuya, H.; Miura, Y.; Asai, K.; Kato, T. Induction of blood-brain barrier properties in immortalized bovine brain endothelial cells by astrocytic factors. Neurosci. Res., 1999, 35(2), 155-164. doi: 10.1016/S0168-0102(99)00079-6 PMID: 10616919
  79. Tran, N.D.; Correale, J.; Schreiber, S.S.; Fisher, M. Transforming growth factor-β mediates astrocyte-specific regulation of brain endothelial anticoagulant factors. Stroke, 1999, 30(8), 1671-1678. doi: 10.1161/01.STR.30.8.1671 PMID: 10436120
  80. Kim, K.K.; Adelstein, R.S.; Kawamoto, S. Identification of neuronal nuclei (NeuN) as Fox-3, a new member of the Fox-1 gene family of splicing factors. J. Biol. Chem., 2009, 284(45), 31052-31061. doi: 10.1074/jbc.M109.052969 PMID: 19713214
  81. Katsetos, C.D.; Herman, M.M.; Mörk, S.J. Class III β‐tubulin in human development and cancer. Cell Motil. Cytoskeleton, 2003, 55(2), 77-96. doi: 10.1002/cm.10116 PMID: 12740870
  82. Aihara, M.; Ishii, S.; Kume, K.; Shimizu, T. Interaction between neurone and microglia mediated by platelet‐activating factor. Genes Cells, 2000, 5(5), 397-406. doi: 10.1046/j.1365-2443.2000.00333.x PMID: 10886367
  83. Tan, Y.L.; Yuan, Y.; Tian, L. Microglial regional heterogeneity and its role in the brain. Mol. Psychiatry, 2020, 25(2), 351-367. doi: 10.1038/s41380-019-0609-8 PMID: 31772305
  84. Biber, K.; Owens, T.; Boddeke, E. What is microglia neurotoxicity (Not)? Glia, 2014, 62(6), 841-854. doi: 10.1002/glia.22654 PMID: 24590682
  85. Lai, A.Y.; Dhami, K.S.; Dibal, C.D.; Todd, K.G. Neonatal rat microglia derived from different brain regions have distinct activation responses. Neuron Glia Biol., 2011, 7(1), 5-16. doi: 10.1017/S1740925X12000154 PMID: 22857737
  86. Katsumoto, A.; Lu, H.; Miranda, A.S.; Ransohoff, R.M. Ontogeny and functions of central nervous system macrophages. J. Immunol., 2014, 193(6), 2615-2621. doi: 10.4049/jimmunol.1400716 PMID: 25193935
  87. Ajami, B.; Bennett, J.L.; Krieger, C.; Tetzlaff, W.; Rossi, F.M.V. Local self-renewal can sustain CNS microglia maintenance and function throughout adult life. Nat. Neurosci., 2007, 10(12), 1538-1543. doi: 10.1038/nn2014 PMID: 18026097
  88. Kierdorf, K.; Erny, D.; Goldmann, T.; Sander, V.; Schulz, C.; Perdiguero, E.G.; Wieghofer, P.; Heinrich, A.; Riemke, P.; Hölscher, C.; Müller, D.N.; Luckow, B.; Brocker, T.; Debowski, K.; Fritz, G.; Opdenakker, G.; Diefenbach, A.; Biber, K.; Heikenwalder, M.; Geissmann, F.; Rosenbauer, F.; Prinz, M. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat. Neurosci., 2013, 16(3), 273-280. doi: 10.1038/nn.3318 PMID: 23334579
  89. Davalos, D.; Grutzendler, J.; Yang, G.; Kim, J.V.; Zuo, Y.; Jung, S.; Littman, D.R.; Dustin, M.L.; Gan, W.B. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci., 2005, 8(6), 752-758. doi: 10.1038/nn1472 PMID: 15895084
  90. Thurgur, H.; Pinteaux, E. Microglia in the neurovascular nnit: Blood-brain barrier-microglia interactions after central nervous system disorders. Neuroscience, 2019, 405, 55-67. doi: 10.1016/j.neuroscience.2018.06.046 PMID: 31007172
  91. Grossmann, R.; Stence, N.; Carr, J.; Fuller, L.; Waite, M.; Dailey, M.E. Juxtavascular microglia migrate along brain microvessels following activation during early postnatal development. Glia, 2002, 37(3), 229-240. doi: 10.1002/glia.10031 PMID: 11857681
  92. Kabba, J.A.; Xu, Y.; Christian, H.; Ruan, W.; Chenai, K.; Xiang, Y.; Zhang, L.; Saavedra, J.M.; Pang, T. Microglia: housekeeper of the central nervous system. Cell. Mol. Neurobiol., 2018, 38(1), 53-71. doi: 10.1007/s10571-017-0504-2 PMID: 28534246
  93. Ito, D.; Imai, Y.; Ohsawa, K.; Nakajima, K.; Fukuuchi, Y.; Kohsaka, S. Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res. Mol. Brain Res., 1998, 57(1), 1-9. doi: 10.1016/S0169-328X(98)00040-0 PMID: 9630473
  94. Carson, M.J.; Doose, J.M.; Melchior, B.; Schmid, C.D.; Ploix, C.C. CNS immune privilege: Hiding in plain sight. Immunol. Rev., 2006, 213(1), 48-65. doi: 10.1111/j.1600-065X.2006.00441.x PMID: 16972896
  95. Engelhardt, B.; Carare, R.O.; Bechmann, I.; Flügel, A.; Laman, J.D.; Weller, R.O. Vascular, glial, and lymphatic immune gateways of the central nervous system. Acta Neuropathol., 2016, 132(3), 317-338. doi: 10.1007/s00401-016-1606-5 PMID: 27522506
  96. Nishioku, T.; Matsumoto, J.; Dohgu, S.; Sumi, N.; Miyao, K.; Takata, F.; Shuto, H.; Yamauchi, A.; Kataoka, Y. Tumor necrosis factor-α mediates the blood-brain barrier dysfunction induced by activated microglia in mouse brain microvascular endothelial cells. J. Pharmacol. Sci., 2010, 112(2), 251-254. doi: 10.1254/jphs.09292SC PMID: 20118615
  97. Yang, Y.; Salayandia, V.M.; Thompson, J.F.; Yang, L.Y.; Estrada, E.Y.; Yang, Y. Attenuation of acute stroke injury in rat brain by minocycline promotes blood-brain barrier remodeling and alternative microglia/macrophage activation during recovery. J. Neuroinflammation, 2015, 12(1), 26. doi: 10.1186/s12974-015-0245-4 PMID: 25889169
  98. Nakajima, K.; Tohyama, Y.; Maeda, S.; Kohsaka, S.; Kurihara, T. Neuronal regulation by which microglia enhance the production of neurotrophic factors for GABAergic, catecholaminergic, and cholinergic neurons. Neurochem. Int., 2007, 50(6), 807-820. doi: 10.1016/j.neuint.2007.02.006 PMID: 17459525
  99. Abbott, N.J. Anatomy and physiology of the blood - brain barriers. In: Drug delivery to the brain AAPS Advances in the Pharmaceutical Sciences Series; Hammarlund-Udenaes, M.; de Lange, E.; Thorne, R., Eds.; Springer: New York, NY, 2014. doi: 10.1007/978-1-4614-9105-7_1
  100. 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. doi: 10.1177/0271678X16630991 PMID: 26868179
  101. Annunziata, P.; Cioni, C.; Toneatto, S.; Paccagnini, E. HIV-1 gp120 increases the permeability of rat brain endothelium cultures by a mechanism involving substance P. AIDS, 1998, 12(18), 2377-2385. doi: 10.1097/00002030-199818000-00006 PMID: 9875575
  102. Chen, Y.; McCarron, R.M.; Azzam, N.; Bembry, J.; Reutzler, C.; Lenz, F.A.; Spatz, M. Endothelin-1 and nitric oxide affect human cerebromicrovascular endothelial responses and signal transduction. Acta Neurochir. Suppl., 2000, 76, 131-135. doi: 10.1007/978-3-7091-6346-7_27 PMID: 11449992
  103. Št’astný, F.; Škultétyová, I.; Pliss, L.; Ježová, D. Quinolinic acid enhances permeability of rat brain microvessels to plasma albumin. Brain Res. Bull., 2000, 53(4), 415-420. doi: 10.1016/S0361-9230(00)00368-3 PMID: 11136997
  104. Chapouly, C.; Tadesse Argaw, A.; Horng, S.; Castro, K.; Zhang, J.; Asp, L.; Loo, H.; Laitman, B.M.; Mariani, J.N.; Straus Farber, R.; Zaslavsky, E.; Nudelman, G.; Raine, C.S.; John, G.R. Astrocytic TYMP and VEGFA drive blood-brain barrier opening in inflammatory central nervous system lesions. Brain, 2015, 138(6), 1548-1567. doi: 10.1093/brain/awv077 PMID: 25805644
  105. Yang, R.; Liu, W.; Miao, L.; Yang, X.; Fu, J.; Dou, B.; Cai, A.; Zong, X.; Tan, C.; Chen, H.; Wang, X. Induction of VEGFA and Snail-1 by meningitic Escherichia coli mediates disruption of the blood-brain barrier. Oncotarget, 2016, 7(39), 63839-63855. doi: 10.18632/oncotarget.11696 PMID: 27588479
  106. Argaw, A.T.; Gurfein, B.T.; Zhang, Y.; Zameer, A.; John, G.R. VEGF-mediated disruption of endothelial CLN-5 promotes blood-brain barrier breakdown. Proc. Natl. Acad. Sci., 2009, 106(6), 1977-1982. doi: 10.1073/pnas.0808698106 PMID: 19174516
  107. Argaw, A.T.; Asp, L.; Zhang, J.; Navrazhina, K.; Pham, T.; Mariani, J.N.; Mahase, S.; Dutta, D.J.; Seto, J.; Kramer, E.G.; Ferrara, N.; Sofroniew, M.V.; John, G.R. Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease. J. Clin. Invest., 2012, 122(7), 2454-2468. doi: 10.1172/JCI60842 PMID: 22653056
  108. Carmen-Orozco, R.P.; Dávila-Villacorta, D.G.; Cauna, Y.; Bernal-Teran, E.G.; Bitterfeld, L.; Sutherland, G.L.; Chile, N.; Céliz, R.H.; Ferrufino-Schmidt, M.C.; Gavídia, C.M.; Sterling, C.R.; García, H.H.; Gilman, R.H.; Verástegui, M.R. Blood-brain barrier disruption and angiogenesis in a rat model for neurocysticercosis. J. Neurosci. Res., 2019, 97(2), 137-148. doi: 10.1002/jnr.24335 PMID: 30315659
  109. Corada, M.; Mariotti, M.; Thurston, G.; Smith, K.; Kunkel, R.; Brockhaus, M.; Lampugnani, M.G.; Martin-Padura, I.; Stoppacciaro, A.; Ruco, L.; McDonald, D.M.; Ward, P.A.; Dejana, E. Vascular endothelial-cadherin is an important determinant of microvascular integrity in vivo. Proc. Natl. Acad. Sci., 1999, 96(17), 9815-9820. doi: 10.1073/pnas.96.17.9815 PMID: 10449777
  110. Vestweber, D. VE-Cadherin. Arterioscler. Thromb. Vasc. Biol., 2008, 28(2), 223-232. doi: 10.1161/ATVBAHA.107.158014 PMID: 18162609
  111. Coureuil, M.; Mikaty, G.; Miller, F.; Lécuyer, H.; Bernard, C.; Bourdoulous, S. Meningococcal type IV pili recruit the polarity complex to cross the brain endothelium. Science, 2009, 325(5936), 83-87. doi: 10.1126/science.1173196
  112. Song, L.; Ge, S.; Pachter, J.S. Caveolin-1 regulates expression of junction-associated proteins in brain microvascular endothelial cells. Blood, 2007, 109(4), 1515-1523. doi: 10.1182/blood-2006-07-034009 PMID: 17023578
  113. Nusrat, A.; Parkos, C.A.; Verkade, P.; Foley, C.S.; Liang, T.W.; Innis-Whitehouse, W.; Eastburn, K.K.; Madara, J.L. Tight junctions are membrane microdomains. J. Cell Sci., 2000, 113(10), 1771-1781. doi: 10.1242/jcs.113.10.1771 PMID: 10769208
  114. Alves, J.L. Blood-brain barrier and traumatic brain injury. J. Neurosci. Res., 2014, 92(2), 141-147. doi: 10.1002/jnr.23300 PMID: 24327344
  115. Tuttolomondo, A.; Di Raimondo, D.; di Sciacca, R.; Pinto, A.; Licata, G. Inflammatory cytokines in acute ischemic stroke. Curr. Pharm. Des., 2008, 14(33), 3574-3589. doi: 10.2174/138161208786848739 PMID: 19075734
  116. Song, L.; Pachter, J.S. Monocyte chemoattractant protein-1 alters expression of tight junction-associated proteins in brain microvascular endothelial cells. Microvasc. Res., 2004, 67(1), 78-89. doi: 10.1016/j.mvr.2003.07.001 PMID: 14709405
  117. Stamatovic, S.M.; Keep, R.F.; Kunkel, S.L.; Andjelkovic, A.V. Potential role of MCP-1 in endothelial cell tight junction ‘opening’: Signaling via Rho and Rho kinase. J. Cell Sci., 2003, 116(22), 4615-4628. doi: 10.1242/jcs.00755 PMID: 14576355
  118. dos Santos, A.C.; Barsante, M.M.; Esteves Arantes, R.M.; Bernard, C.C.A.; Teixeira, M.M.; Carvalho-Tavares, J. CCL2 and CCL5 mediate leukocyte adhesion in experimental autoimmune encephalomyelitis-an intravital microscopy study. J. Neuroimmunol., 2005, 162(1-2), 122-129. doi: 10.1016/j.jneuroim.2005.01.020 PMID: 15833367
  119. Chui, R.; Dorovini-Zis, K. Regulation of CCL2 and CCL3 expression in human brain endothelial cells by cytokines and lipopolysaccharide. J. Neuroinflammation, 2010, 7(1), 1. doi: 10.1186/1742-2094-7-1 PMID: 20047691
  120. Glabinski, A.R.; Balasingam, V.; Tani, M.; Kunkel, S.L.; Strieter, R.M.; Yong, V.W. Chemokine monocyte chemoattractant protein-1 is expressed by astrocytes after mechanical injury to the brain. J. Immunol., 1996, 156(11), 4363-4368. doi: 10.4049/jimmunol.156.11.4363
  121. Takeshita, Y.; Ransohoff, R.M. Inflammatory cell trafficking across the blood-brain barrier: Chemokine regulation and in vitro models. Immunol. Rev., 2012, 248(1), 228-239. doi: 10.1111/j.1600-065X.2012.01127.x PMID: 22725965
  122. 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. doi: 10.1177/0271678X18788769 PMID: 30058456
  123. 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. doi: 10.1186/s12987-020-00202-7 PMID: 32677965
  124. 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. doi: 10.1186/s12987-020-00183-7 PMID: 32178700
  125. Hajal, C.; Campisi, M.; Mattu, C.; Chiono, V.; Kamm, R.D. In vitro models of molecular and nano-particle transport across the blood-brain barrier. Biomicrofluidics, 2018, 12(4), 042213. doi: 10.1063/1.5027118 PMID: 29887937
  126. 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. doi: 10.2147/DDDT.S218708 PMID: 31695329
  127. Gastfriend, B.D.; Palecek, S.P.; Shusta, E.V. Modeling the blood-brain barrier: Beyond the endothelial cells. Curr. Opin. Biomed. Eng., 2018, 5, 6-12. doi: 10.1016/j.cobme.2017.11.002 PMID: 29915815
  128. Herland, A.; van der Meer, A.D.; FitzGerald, E.A.; Park, T.E.; Sleeboom, J.J.F.; 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. doi: 10.1371/journal.pone.0150360 PMID: 26930059
  129. Santaguida, S.; Janigro, D.; Hossain, M.; Oby, E.; Rapp, E.; Cucullo, L. Side by side comparison between dynamic versus static models of blood-brain barrier in vitro: A permeability study. Brain Res., 2006, 1109(1), 1-13. doi: 10.1016/j.brainres.2006.06.027 PMID: 16857178
  130. Kaisar, M.A.; Sajja, R.K.; Prasad, S.; Abhyankar, V.V.; Liles, T.; Cucullo, L. New experimental models of the blood-brain barrier for CNS drug discovery. Expert Opin. Drug Discov., 2017, 12(1), 89-103. doi: 10.1080/17460441.2017.1253676 PMID: 27782770
  131. Jiang, L.; Li, S.; Zheng, J.; Li, Y.; Huang, H. Recent progress in microfluidic models of the blood-brain barrier. Micromachines, 2019, 10(6), 375. doi: 10.3390/mi10060375 PMID: 31195652
  132. Naik, P.; Cucullo, L. In vitro blood-brain barrier models: Current and perspective technologies. J. Pharm. Sci., 2012, 101(4), 1337-1354. doi: 10.1002/jps.23022 PMID: 22213383
  133. Roberts, L.M.; Black, D.S.; Raman, C.; Woodford, K.; Zhou, M.; Haggerty, J.E.; Yan, A.T.; Cwirla, S.E.; Grindstaff, K.K. Subcellular localization of transporters along the rat blood-brain barrier and blood-cerebral-spinal fluid barrier by in vivo biotinylation. Neuroscience, 2008, 155(2), 423-438. doi: 10.1016/j.neuroscience.2008.06.015 PMID: 18619525
  134. Ghosh, C.; Gonzalez-Martinez, J.; Hossain, M.; Cucullo, L.; Fazio, V.; Janigro, D.; Marchi, N. Pattern of P450 expression at the human blood-brain barrier: Roles of epileptic condition and laminar flow. Epilepsia, 2010, 51(8), 1408-1417. doi: 10.1111/j.1528-1167.2009.02428.x PMID: 20074231
  135. Ghosh, C.; Puvenna, V.; Gonzalez-Martinez, J.; Janigro, D.; Marchi, N. Blood-brain barrier P450 enzymes and multidrug transporters in drug resistance: A synergistic role in neurological diseases. Curr. Drug Metab., 2011, 12(8), 742-749. doi: 10.2174/138920011798357051 PMID: 21568937
  136. Dauchy, S.; Dutheil, F.; Weaver, R.J.; Chassoux, F.; Daumas-Duport, C.; Couraud, P.O.; Scherrmann, J.M.; De Waziers, I.; Declèves, X. ABC transporters, cytochromes P450 and their main transcription factors: Expression at the human blood-brain barrier. J. Neurochem., 2008, 107(6), 1518-1528. doi: 10.1111/j.1471-4159.2008.05720.x PMID: 19094056
  137. Abbott, N.J.; Romero, I.A. Transporting therapeutics across the blood-brain barrier. Mol. Med. Today, 1996, 2(3), 106-113. doi: 10.1016/1357-4310(96)88720-X PMID: 8796867
  138. Ghazanfari, F.A.; Stewart, R.R. Characteristics of endothelial cells derived from the blood-brain barrier and of astrocytes in culture. Brain Res., 2001, 890(1), 49-65. doi: 10.1016/S0006-8993(00)03053-5 PMID: 11164768
  139. Kido, Y.; Tamai, I.; Nakanishi, T.; Kagami, T.; Hirosawa, I.; Sai, Y.; Tsuji, A. Evaluation of blood-brain barrier transporters by co-culture of brain capillary endothelial cells with astrocytes. Drug Metab. Pharmacokinet., 2002, 17(1), 34-41. doi: 10.2133/dmpk.17.34 PMID: 15618650
  140. Lindroos, B.; Aho, K.L.; Kuokkanen, H.; Räty, S.; Huhtala, H.; Lemponen, R.; Yli-Harja, O.; Suuronen, R.; Miettinen, S. Differential gene expression in adipose stem cells cultured in allogeneic human serum versus fetal bovine serum. Tissue Eng. Part A, 2010, 16(7), 2281-2294. doi: 10.1089/ten.tea.2009.0621 PMID: 20184435
  141. Jancic, C.; Chuluyan, H.E.; Morelli, A.; Larregina, A.; Kolkowski, E.; Saracco, M.; Barboza, M.; Leiva, W.S.; Fainboim, L. Interactions of dendritic cells with fibronectin and endothelial cells. Immunology, 1998, 95(2), 283-290. doi: 10.1046/j.1365-2567.1998.00586.x PMID: 9824488
  142. Syvänen, S.; Lindhe, Ö.; Palner, M.; Kornum, B.R.; Rahman, O.; Långström, B.; Knudsen, G.M.; Hammarlund-Udenaes, M. Species differences in blood-brain barrier transport of three positron emission tomography radioligands with emphasis on P-glycoprotein transport. Drug Metab. Dispos., 2009, 37(3), 635-643. doi: 10.1124/dmd.108.024745 PMID: 19047468
  143. Uchida, Y.; Ohtsuki, S.; Katsukura, Y.; Ikeda, C.; Suzuki, T.; Kamiie, J.; Terasaki, T. Quantitative targeted absolute proteomics of human blood-brain barrier transporters and receptors. J. Neurochem., 2011, 117(2), 333-345. doi: 10.1111/j.1471-4159.2011.07208.x PMID: 21291474
  144. Warren, M.S.; Zerangue, N.; Woodford, K.; Roberts, L.M.; Tate, E.H.; Feng, B.; Li, C.; Feuerstein, T.J.; Gibbs, J.; Smith, B.; de Morais, S.M.; Dower, W.J.; Koller, K.J. Comparative gene expression profiles of ABC transporters in brain microvessel endothelial cells and brain in five species including human. Pharmacol. Res., 2009, 59(6), 404-413. doi: 10.1016/j.phrs.2009.02.007 PMID: 19429473
  145. Löscher, W.; Potschka, H. Role of drug efflux transporters in the brain for drug disposition and treatment of brain diseases. Prog. Neurobiol., 2005, 76(1), 22-76. doi: 10.1016/j.pneurobio.2005.04.006 PMID: 16011870
  146. Bernas, M.J.; Cardoso, F.L.; Daley, S.K.; Weinand, M.E.; Campos, A.R.; Ferreira, A.J.G.; Hoying, J.B.; Witte, M.H.; Brites, D.; Persidsky, Y.; Ramirez, S.H.; Brito, M.A. Establishment of primary cultures of human brain microvascular endothelial cells to provide an in vitro cellular model of the blood-brain barrier. Nat. Protoc., 2010, 5(7), 1265-1272. doi: 10.1038/nprot.2010.76 PMID: 20595955
  147. 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. doi: 10.1096/fj.04-3458fje PMID: 16141364
  148. Marroni, M.; Kight, K.M.; Hossain, M.; Cucullo, L.; Desai, S.Y.; Janigro, D. Dynamic In vitro model of the blood-brain barrier: biology and research protocols; Humana Press: Totowa, NJ, 2003, pp. 419-434. doi: 10.1385/1-59259-419-0:419
  149. Deli, M.A. Blood-brain barrier models BT - Handbook of neurochemistry and molecular neurobiology: neural membranes and transport; Springer US: Boston, MA, 2007, pp. 29-55. doi: 10.1007/978-0-387-30380-2_2
  150. Helms, H.C.; Waagepetersen, H.S.; Nielsen, C.U.; 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(4), 759-770. doi: 10.1208/s12248-010-9237-6 PMID: 20967520
  151. Patabendige, A.; Skinner, R.A.; Abbott, N.J. Establishment of a simplified in vitro porcine blood-brain barrier model with high transendothelial electrical resistance. Brain Res., 2013, 1521, 1-15. doi: 10.1016/j.brainres.2012.06.057 PMID: 22789905
  152. Idris, F.; Muharram, H.S.; Zaini, Z.; Diah, S. Establishment of murine in vitro blood-brain barrier models using immortalized cell lines: Co-cultures of brain endothelial cells, astrocytes, and neurons. bioRxiv, 2018, 435990. doi: 10.1101/435990
  153. Cucullo, L.; Hossain, M.; Rapp, E.; Manders, T.; Marchi, N.; Janigro, D. Development of a humanized in vitro blood-brain barrier model to screen for brain penetration of antiepileptic drugs. Epilepsia, 2007, 48(3), 505-516. doi: 10.1111/j.1528-1167.2006.00960.x PMID: 17326793
  154. Ghosh, C.; Hossain, M.; Solanki, J.; Najm, I.M.; Marchi, N.; Janigro, D. Overexpression of pregnane X and glucocorticoid receptors and the regulation of cytochrome P450 in human epileptic brain endothelial cells. Epilepsia, 2017, 58(4), 576-585. doi: 10.1111/epi.13703 PMID: 28199000
  155. Labus, J.; Häckel, S.; Lucka, L.; Danker, K. Interleukin-1β induces an inflammatory response and the breakdown of the endothelial cell layer in an improved human THBMEC-based in vitro blood-brain barrier model. J. Neurosci. Methods, 2014, 228, 35-45. doi: 10.1016/j.jneumeth.2014.03.002 PMID: 24631939
  156. Srinivasan, B.; Kolli, A.R.; Esch, M.B.; Abaci, H.E.; Shuler, M.L.; Hickman, J.J. TEER measurement techniques for in vitro barrier model systems. SLAS Technol., 2015, 20(2), 107-126. doi: 10.1177/2211068214561025 PMID: 25586998
  157. Crone, C.; Olesen, S.P. Electrical resistance of brain microvascular endothelium. Brain Res., 1982, 241(1), 49-55. doi: 10.1016/0006-8993(82)91227-6 PMID: 6980688
  158. Butt, A.M.; Jones, H.C.; Abbott, N.J. Electrical resistance across the blood‐brain barrier in anaesthetized rats: A developmental study. J. Physiol., 1990, 429(1), 47-62. doi: 10.1113/jphysiol.1990.sp018243 PMID: 2277354
  159. Crone, C.; Christensen, O. Electrical resistance of a capillary endothelium. J. Gen. Physiol., 1981, 77(4), 349-371. doi: 10.1085/jgp.77.4.349 PMID: 7241087
  160. Eigenmann, D.E.; Xue, G.; Kim, K.S.; Moses, A.V.; 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(1), 33. doi: 10.1186/2045-8118-10-33 PMID: 24262108
  161. Veszelka, S.; Tóth, A.; Walter, F.R.; Tóth, A.E.; Gróf, I.; Mészáros, M.; Bocsik, A.; Hellinger, É.; Vastag, M.; Rákhely, G.; Deli, M.A. Comparison of a rat primary cell-based blood-brain barrier model with epithelial and brain endothelial cell lines : Gene expression and drug transport. Front. Mol. Neurosci., 2018, 11, 166. doi: 10.3389/fnmol.2018.00166 PMID: 29872378
  162. Maherally, Z.; Fillmore, H.L.; Tan, S.L.; Tan, S.F.; Jassam, S.A.; Quack, F.I.; Hatherell, K.E.; Pilkington, G.J. Real‐time acquisition of transendothelial electrical resistance in an all‐human, in vitro, 3‐dimensional, blood‐brain barrier model exemplifies tight‐junction integrity. FASEB J., 2018, 32(1), 168-182. doi: 10.1096/fj.201700162R PMID: 28883042
  163. Elbakary, B.; Badhan, R.K.S. A dynamic perfusion based blood-brain barrier model for cytotoxicity testing and drug permeation. Sci. Rep., 2020, 10(1), 3788. doi: 10.1038/s41598-020-60689-w PMID: 32123236
  164. Förster, C.; Burek, M.; Romero, I.A.; Weksler, B.; Couraud, P.O.; Drenckhahn, D. Differential effects of hydrocortisone and TNFα on tight junction proteins in an in vitro model of the human blood-brain barrier. J. Physiol., 2008, 586(7), 1937-1949. doi: 10.1113/jphysiol.2007.146852 PMID: 18258663
  165. Stone, N.L.; England, T.J.; O’Sullivan, S.E. A novel transwell blood brain barrier model using primary human cells. Front. Cell. Neurosci., 2019, 13, 230. doi: 10.3389/fncel.2019.00230 PMID: 31244605
  166. 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. doi: 10.1038/jcbfm.2010.162 PMID: 20842162
  167. Prudhomme, J.G.; Sherman, I.W.; Land, K.M.; Moses, A.V.; Stenglein, S.; Nelson, J.A. Studies of Plasmodium falciparum cytoadherence using immortalized human brain capillary endothelial cells. Int. J. Parasitol., 1996, 26(6), 647-655. doi: 10.1016/0020-7519(96)00027-6 PMID: 8875310
  168. Sano, Y.; Kashiwamura, Y.; Abe, M.; Dieu, L.H.; Huwyler, J.; Shimizu, F.; Haruki, H.; Maeda, T.; Saito, K.; Tasaki, A.; Kanda, T. Stable human brain microvascular endothelial cell line retaining its barrier‐specific nature independent of the passage number. Clin. Exp. Neuroimmunol., 2013, 4(1), 92-103. doi: 10.1111/cen3.12001
  169. Watson, P.M.D.; Paterson, J.C.; Thom, G.; Ginman, U.; Lundquist, S.; Webster, C.I. Modelling the endothelial blood-CNS barriers: A method for the production of robust in vitromodels of the rat blood-brain barrier and blood-spinal cord barrier. BMC Neurosci., 2013, 14(1), 59. doi: 10.1186/1471-2202-14-59 PMID: 23773766
  170. Booth, R.; Kim, H. Characterization of a microfluidic in vitro model of the blood-brain barrier (µBBB). Lab Chip, 2012, 12(10), 1784-1792. doi: 10.1039/c2lc40094d PMID: 22422217
  171. Poller, B.; Gutmann, H.; Krähenbühl, S.; Weksler, B.; Romero, I.; Couraud, P.O.; Tuffin, G.; Drewe, J.; Huwyler, J. The human brain endothelial cell line hCMEC/D3 as a human blood‐brain barrier model for drug transport studies. J. Neurochem., 2008, 107(5), 1358-1368. doi: 10.1111/j.1471-4159.2008.05730.x PMID: 19013850
  172. Camós, S.; Mallolas, J. Experimental models for assaying microvascular endothelial cell pathophysiology in stroke. Molecules, 2010, 15(12), 9104-9134. doi: 10.3390/molecules15129104 PMID: 21150829
  173. Even-Ram, S.; Yamada, K.M. Cell migration in 3D matrix. Curr. Opin. Cell Biol., 2005, 17(5), 524-532. doi: 10.1016/j.ceb.2005.08.015 PMID: 16112853
  174. Cecchelli, R.; Dehouck, B.; Descamps, L.; Fenart, L.; Buée-Scherrer, V.; Duhem, C.; Lundquist, S.; Rentfel, M.; Torpier, G.; Dehouck, M.P. In vitro model for evaluating drug transport across the blood-brain barrier. Adv. Drug Deliv. Rev., 1999, 36(2-3), 165-178. doi: 10.1016/S0169-409X(98)00083-0 PMID: 10837714
  175. Wuest, D.M.; Wing, A.M.; Lee, K.H. Membrane configuration optimization for a murine in vitro blood-brain barrier model. J. Neurosci. Methods, 2013, 212(2), 211-221. doi: 10.1016/j.jneumeth.2012.10.016 PMID: 23131353
  176. Chiu, J.J.; Chen, L.J.; Chang, S.F.; Lee, P.L.; Lee, C.I.; Tsai, M.C.; Lee, D.Y.; Hsieh, H.P.; Usami, S.; Chien, S. Shear stress inhibits smooth muscle cell-induced inflammatory gene expression in endothelial cells: role of NF-kappaB. Arterioscler. Thromb. Vasc. Biol., 2005, 25(5), 963-969. doi: 10.1161/01.ATV.0000159703.43374.19 PMID: 15718492
  177. Desai, S.Y.; Marroni, M.; Cucullo, L.; Krizanac-Bengez, L.; Mayberg, M.R.; Hossain, M.T.; Grant, G.G.; Janigro, D. Mechanisms of endothelial survival under shear stress. Endothelium, 2002, 9(2), 89-102. doi: 10.1080/10623320212004 PMID: 12200960
  178. DeStefano, J.G.; Williams, A.; Wnorowski, A.; Yimam, N.; Searson, P.C.; Wong, A.D. Real-time quantification of endothelial response to shear stress and vascular modulators. Integr. Biol., 2017, 9(4), 362-374. doi: 10.1039/C7IB00023E PMID: 28345713
  179. Partyka, P.P.; Godsey, G.A.; Galie, J.R.; Kosciuk, M.C.; Acharya, N.K.; Nagele, R.G.; Galie, P.A. Mechanical stress regulates transport in a compliant 3D model of the blood-brain barrier. Biomaterials, 2017, 115, 30-39. doi: 10.1016/j.biomaterials.2016.11.012 PMID: 27886553
  180. Kaya, M.; Ahishali, B. Assessment of permeability in barrier type of endothelium in brain using tracers: Evans blue, sodium fluorescein, and horseradish peroxidase. In: Permeability Barrier: Methods and Protocols, Methods in Molecular Biology; Turksen, K., Ed.; Humana Press, 2011; pp. 369-382. doi: 10.1007/978-1-61779-191-8_25
  181. Wilhelm, I.; Fazakas, C.; Krizbai, I. In vitro models of the blood-brain barrier. Acta Neurobiol. Exp., 2011, 71(1), 113-128. doi: 10.55782/ane-2011-1828 PMID: 21499332
  182. Obermeier, B.; Daneman, R.; Ransohoff, R.M. Development, maintenance and disruption of the blood-brain barrier. Nat. Med., 2013, 19(12), 1584-1596. doi: 10.1038/nm.3407 PMID: 24309662
  183. Czupalla, C.J.; Liebner, S.; Devraj, K. In vitro models of the blood-brain barrier. In: Cerebral angiogenesis methods in molecular biology; Milner, R., Ed.; Humana Press: New York, NY, 2014; pp. 415-437. doi: 10.1007/978-1-4939-0320-7_34
  184. Rahman, N.A.; Sharudin, A.; Diah, S.; Muharram, S.H. Serotyping of Brunei pneumococcal clinical strains and the investigation of their capability to adhere and invade a brain endothelium model. Microb. Pathog., 2017, 110, 352-358. doi: 10.1016/j.micpath.2017.07.021 PMID: 28711510
  185. Williams-Medina, A.; Deblock, M.; Janigro, D. In vitro models of the blood-brain barrier: Tools in translational medicine. Front. Med. Technol., 2021, 2, 623950. doi: 10.3389/fmedt.2020.623950 PMID: 35047899
  186. Alimonti, J.B.; Ribecco-Lutkiewicz, M.; Sodja, C.; Jezierski, A.; Stanimirovic, D.B.; Liu, Q.; Haqqani, A.S.; Conlan, W.; Bani-Yaghoub, M. Zika virus crosses an in vitro human blood brain barrier model. Fluids Barriers CNS, 2018, 15(1), 15. doi: 10.1186/s12987-018-0100-y PMID: 29759080
  187. Ribecco-Lutkiewicz, M.; Sodja, C.; Haukenfrers, J.; Haqqani, A.S.; Ly, D.; Zachar, P.; Baumann, E.; Ball, M.; Huang, J.; Rukhlova, M.; Martina, M.; Liu, Q.; Stanimirovic, D.; Jezierski, A.; Bani-Yaghoub, M. A novel human induced pluripotent stem cell blood-brain barrier model: Applicability to study antibody-triggered receptor-mediated transcytosis. Sci. Rep., 2018, 8(1), 1873. doi: 10.1038/s41598-018-19522-8 PMID: 29382846
  188. Wong, M.K.; Gotlieb, A.I. Endothelial cell monolayer integrity. I. Characterization of dense peripheral band of microfilaments. Arteriosclerosis, 1986, 6(2), 212-219. doi: 10.1161/01.ATV.6.2.212 PMID: 3954675
  189. Kazakoff, P.W.; McGuire, T.R.; Hoie, E.B.; Cano, M.; Iversen, P.L. An in vitro model for endothelial permeability: Assessment of monolayer integrity. Vitr Cell Dev Biol - Anim, 1995, 31(11), 846-852.
  190. Cooray, H.C.; Blackmore, C.G.; Maskell, L.; Barrand, M.A. Localisation of breast cancer resistance protein in microvessel endothelium of human brain. Neuroreport, 2002, 13(16), 2059-2063. doi: 10.1097/00001756-200211150-00014 PMID: 12438926
  191. Zhang, W.; Mojsilovic-Petrovic, J.; Andrade, M.F.; Zhang, H.; Ball, M.; Stanimirovic, D.B. Expression and functional characterization of ABCG2 in brain endothelial cells and vessels. FASEB J., 2003, 17(14), 1-24. doi: 10.1096/fj.02-1131fje PMID: 12958161
  192. Kido, Y.; Tamai, I.; Okamoto, M.; Suzuki, F.; Tsuji, A. Functional clarification of MCT1-mediated transport of monocarboxylic acids at the blood-brain barrier using in vitro cultured cells and in vivo BUI studies. Pharm. Res., 2000, 17(1), 55-62. doi: 10.1023/A:1007518525161 PMID: 10714609
  193. Zheng, P.P.; Romme, E.; Spek, P.J.; Dirven, C.M.F.; Willemsen, R.; Kros, J.M. Glut1/SLC2A1 is crucial for the development of the blood‐brain barrier in vivo. Ann. Neurol., 2010, 68(6), 835-844. doi: 10.1002/ana.22318 PMID: 21194153
  194. Hersom, M.; Helms, H.C.; Pretzer, N.; Goldeman, C.; Jensen, A.I.; Severin, G.; Nielsen, M.S.; Holm, R.; Brodin, B. Transferrin receptor expression and role in transendothelial transport of transferrin in cultured brain endothelial monolayers. Mol. Cell. Neurosci., 2016, 76, 59-67. doi: 10.1016/j.mcn.2016.08.009 PMID: 27567687
  195. Hayashi, Y.; Nomura, M.; Yamagishi, S.I.; Harada, S.I.; Yamashita, J.; Yamamoto, H. Induction of various blood-brain barrier properties in non-neural endothelial cells by close apposition to co-cultured astrocytes. Glia, 1997, 19(1), 13-26. doi: 10.1002/(SICI)1098-1136(199701)19:13.0.CO;2-B PMID: 8989564
  196. Zhao, Z.; Nelson, A.R.; Betsholtz, C.; Zlokovic, B.V. Establishment and dysfunction of the blood-brain barrier. Cell, 2015, 163(5), 1064-1078. doi: 10.1016/j.cell.2015.10.067 PMID: 26590417
  197. Bazzoni, G.; Dejana, E. Endothelial cell-to-cell junctions: Molecular organization and role in vascular homeostasis. Physiol. Rev., 2004, 84(3), 869-901. doi: 10.1152/physrev.00035.2003 PMID: 15269339
  198. Simi, A.; Tsakiri, N.; Wang, P.; Rothwell, N.J. Interleukin-1 and inflammatory neurodegeneration. Biochem. Soc. Trans., 2007, 35(5), 1122-1126. doi: 10.1042/BST0351122 PMID: 17956293
  199. Shaftel, S.S.; Griffin, W.S.T.; O’Banion, M.K. The role of interleukin-1 in neuroinflammation and Alzheimer disease: An evolving perspective. J. Neuroinflammation, 2008, 5(1), 7. doi: 10.1186/1742-2094-5-7 PMID: 18302763
  200. Lutgendorf, M.A.; Ippolito, D.L.; Mesngon, M.T.; Tinnemore, D.; Dehart, M.J.; Dolinsky, B.M.; Napolitano, P.G. Effect of dexamethasone administered with magnesium sulfate on inflammation-mediated degradation of the blood-brain barrier using an in vitro model. Reprod. Sci., 2014, 21(4), 483-491. doi: 10.1177/1933719113503410 PMID: 24077438
  201. Burkert, K.; Moodley, K.; Angel, C.E.; Brooks, A.; Graham, E.S. Detailed analysis of inflammatory and neuromodulatory cytokine secretion from human NT2 astrocytes using multiplex bead array. Neurochem. Int., 2012, 60(6), 573-580. doi: 10.1016/j.neuint.2011.09.002 PMID: 21939706
  202. Shigemoto-Mogami, Y.; Hoshikawa, K.; Sato, K. Activated microglia disrupt the blood-brain barrier and induce chemokines and cytokines in a rat in vitro model. Front. Cell. Neurosci., 2018, 12, 494. doi: 10.3389/fncel.2018.00494 PMID: 30618641
  203. Banks, W.A.; Gray, A.M.; Erickson, M.A.; Salameh, T.S.; Damodarasamy, M.; Sheibani, N.; Meabon, J.S.; Wing, E.E.; Morofuji, Y.; Cook, D.G.; Reed, M.J. Lipopolysaccharide-induced blood-brain barrier disruption: Roles of cyclooxygenase, oxidative stress, neuroinflammation, and elements of the neurovascular unit. J. Neuroinflammation, 2015, 12(1), 223. doi: 10.1186/s12974-015-0434-1 PMID: 26608623
  204. Greenwood, J.; Howes, R.; Lightman, S. The blood-retinal barrier in experimental autoimmune uveoretinitis. Leukocyte interactions and functional damage. Lab. Invest., 1994, 70(1), 39-52. PMID: 8302017
  205. Abadier, M.; Jahromi, H.N.; Alves, C.L.; Boscacci, R.; Vestweber, D.; Barnum, S.; Deutsch, U.; Engelhardt, B.; Lyck, R. Cell surface levels of endothelial ICAM‐1 influence the transcellular or paracellular T‐cell diapedesis across the blood-brain barrier. Eur. J. Immunol., 2015, 45(4), 1043-1058. doi: 10.1002/eji.201445125 PMID: 25545837
  206. Kim, K.S. Current concepts on the pathogenesis of Escherichia coli meningitis. Curr. Opin. Infect. Dis., 2012, 25(3), 273-278. doi: 10.1097/QCO.0b013e3283521eb0 PMID: 22395761
  207. Yang, R.C.; Qu, X.Y.; Xiao, S.Y.; Li, L.; Xu, B.J.; Fu, J.Y.; Lv, Y.J.; Amjad, N.; Tan, C.; Kim, K.S.; Chen, H.C.; Wang, X.R. Meningitic Escherichia coli-induced upregulation of PDGF-B and ICAM-1 aggravates blood-brain barrier disruption and neuroinflammatory response. J. Neuroinflammation, 2019, 16(1), 101. doi: 10.1186/s12974-019-1497-1 PMID: 31092253
  208. Wang, X.; Maruvada, R.; Morris, A.J.; Liu, J.O.; Wolfgang, M.J.; Baek, D.J.; Bittman, R.; Kim, K.S. Sphingosine 1-phosphate activation of EGFR as a novel target for meningitic Escherichia coli penetration of the blood-brain barrier. PLoS Pathog., 2016, 12(10), e1005926. doi: 10.1371/journal.ppat.1005926 PMID: 27711202
  209. Iovino, F.; Orihuela, C.J.; Moorlag, H.E.; Molema, G.; Bijlsma, J.J.E. Interactions between blood-borne Streptococcus pneumoniae and the blood-brain barrier preceding meningitis. PLoS One, 2013, 8(7), e68408. doi: 10.1371/journal.pone.0068408 PMID: 23874613
  210. Orihuela, C.J.; Mahdavi, J.; Thornton, J.; Mann, B.; Wooldridge, K.G.; Abouseada, N.; Oldfield, N.J.; Self, T.; Ala’Aldeen, D.A.A.; Tuomanen, E.I. Laminin receptor initiates bacterial contact with the blood brain barrier in experimental meningitis models. J. Clin. Invest., 2009, 119(6), 1638-1646. doi: 10.1172/JCI36759 PMID: 19436113
  211. Henderson, B.; Nair, S.; Pallas, J.; Williams, M.A. Fibronectin: A multidomain host adhesin targeted by bacterial fibronectin-binding proteins. FEMS Microbiol. Rev., 2011, 35(1), 147-200. doi: 10.1111/j.1574-6976.2010.00243.x PMID: 20695902
  212. Kim, B.J.; Bee, O.B.; McDonagh, M.A.; Stebbins, M.J.; Palecek, S.P.; Doran, K.S.; Shusta, E.V. Modeling group B streptococcus and blood-brain barrier interaction by using induced pluripotent stem cell-derived brain endothelial cells. MSphere, 2017, 2(6), e00398-e17. doi: 10.1128/mSphere.00398-17 PMID: 29104935
  213. Mu, R.; Kim, B.J.; Paco, C.; Del Rosario, Y.; Courtney, H.S.; Doran, K.S. Identification of a group B streptococcal fibronectin binding protein, SfbA, that contributes to invasion of brain endothelium and development of meningitis. Infect. Immun., 2014, 82(6), 2276-2286. doi: 10.1128/IAI.01559-13 PMID: 24643538
  214. Ferguson, M.C.; Saul, S.; Fragkoudis, R.; Weisheit, S.; Cox, J.; Patabendige, A.; Sherwood, K.; Watson, M.; Merits, A.; Fazakerley, J.K. Ability of the encephalitic arbovirus Semliki Forest virus to cross the blood-brain barrier is determined by the charge of the E2 glycoprotein. J. Virol., 2015, 89(15), 7536-7549. doi: 10.1128/JVI.03645-14 PMID: 25972559
  215. Bourgonje, A.R.; Abdulle, A.E.; Timens, W.; Hillebrands, J.L.; Navis, G.J.; Gordijn, S.J.; Bolling, M.C.; Dijkstra, G.; Voors, A.A.; Osterhaus, A.D.M.E.; van der Voort, P.H.J.; Mulder, D.J.; van Goor, H. Angiotensin‐converting enzyme 2 (ACE2), SARS‐COV‐2 and the pathophysiology of coronavirus disease 2019 (COVID‐19). J. Pathol., 2020, 251(3), 228-248. doi: 10.1002/path.5471 PMID: 32418199
  216. Doobay, M.F.; Talman, L.S.; Obr, T.D.; Tian, X.; Davisson, R.L.; Lazartigues, E. Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2007, 292(1), R373-R381. doi: 10.1152/ajpregu.00292.2006 PMID: 16946085
  217. Hamming, I.; Timens, W.; Bulthuis, M.L.C.; Lely, A.T.; Navis, G.J.; van Goor, H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J. Pathol., 2004, 203(2), 631-637. doi: 10.1002/path.1570 PMID: 15141377
  218. Solomon, I.H.; Normandin, E.; Bhattacharyya, S.; Mukerji, S.S.; Keller, K.; Ali, A.S.; Adams, G.; Hornick, J.L.; Padera, R.F., Jr; Sabeti, P. Neuropathological features of COVID-19. N. Engl. J. Med., 2020, 383(10), 989-992. doi: 10.1056/NEJMc2019373 PMID: 32530583
  219. Wang, Y.; Cao, Y.; Mangalam, A.K.; Guo, Y.; LaFrance-Corey, R.G.; Gamez, J.D.; Atanga, P.A.; Clarkson, B.D.; Zhang, Y.; Wang, E.; Angom, R.S.; Dutta, K.; Ji, B.; Pirko, I.; Lucchinetti, C.F.; Howe, C.L.; Mukhopadhyay, D. Neuropilin-1 modulates interferon-γ-stimulated signaling in brain microvascular endothelial cells. J. Cell Sci., 2016, 129(20), 3911-3921. doi: 10.1242/jcs.190702
  220. Burks, S.M.; Rosas-Hernandez, H.; Ramirez-Lee, A.M.; Cuevas, E.; Talpos, J.C. Can SARS-CoV-2 infect the central nervous system via the olfactory bulb or the blood-brain barrier? Brain Behav. Immun., 2021, 95, 7-14. doi: 10.1016/j.bbi.2020.12.031 PMID: 33412255
  221. Atlas, H.P.. The human protein atlas., 2021. https://www.proteinatlas.org/
  222. Cabirac, G.F.; Murray, R.S.; McLaughlin, L.B.; Skolnick, D.M.; Hogue, B.; Dorovini-Zis, K.; Didier, P.J. In vitro interaction of coronaviruses with primate and human brain microvascular endothelial cells. Adv. Exp. Med. Biol., 1995, 380, 79-88. doi: 10.1007/978-1-4615-1899-0_11 PMID: 8830550
  223. Nuovo, G.J.; Magro, C.; Shaffer, T.; Awad, H.; Suster, D.; Mikhail, S.; He, B.; Michaille, J.J.; Liechty, B.; Tili, E. Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein. Ann. Diagn. Pathol., 2021, 51, 151682. doi: 10.1016/j.anndiagpath.2020.151682 PMID: 33360731
  224. Reynolds, J.L.; Mahajan, S.D. SARS-COV2 alters blood brain barrier integrity contributing to neuro-inflammation. J. Neuroimmune Pharmacol., 2021, 16(1), 4-6. doi: 10.1007/s11481-020-09975-y PMID: 33405097
  225. Varga, Z.; Flammer, A.J.; Steiger, P.; Haberecker, M.; Andermatt, R.; Zinkernagel, A.S.; Mehra, M.R.; Schuepbach, R.A.; Ruschitzka, F.; Moch, H. Endothelial cell infection and endotheliitis in COVID-19. Lancet, 2020, 395(10234), 1417-1418. doi: 10.1016/S0140-6736(20)30937-5 PMID: 32325026
  226. Buzhdygan, T.P.; DeOre, B.J.; Baldwin-Leclair, A.; Bullock, T.A.; McGary, H.M.; Khan, J.A.; Razmpour, R.; Hale, J.F.; Galie, P.A.; Potula, R.; Andrews, A.M.; Ramirez, S.H. The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier. Neurobiol. Dis., 2020, 146, 105131. doi: 10.1016/j.nbd.2020.105131 PMID: 33053430
  227. Al-Harthi, L.; Campbell, E.; Schneider, J.A.; Bennett, D.A. What HIV in the brain can teach us about SARS-CoV-2 neurological complications? AIDS Res. Hum. Retroviruses, 2021, 37(4), 255-265. doi: 10.1089/aid.2020.0161 PMID: 32683890
  228. Edwards, J.A.; Denis, F.; Talbot, P.J. Activation of glial cells by human coronavirus OC43 infection. J. Neuroimmunol., 2000, 108(1-2), 73-81. doi: 10.1016/S0165-5728(00)00266-6 PMID: 10900340
  229. Paniz-Mondolfi, A.; Bryce, C.; Grimes, Z.; Gordon, R.E.; Reidy, J.; Lednicky, J.; Sordillo, E.M.; Fowkes, M. Central nervous system involvement by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). J. Med. Virol., 2020, 92(7), 699-702. doi: 10.1002/jmv.25915 PMID: 32314810
  230. Sardu, C.; Gambardella, J.; Morelli, M.B.; Wang, X.; Marfella, R.; Santulli, G. Hypertension, thrombosis, kidney failure, and diabetes: Is COVID-19 an endothelial disease? a comprehensive evaluation of clinical and basic evidence. J. Clin. Med., 2020, 9(5), 1417. doi: 10.3390/jcm9051417 PMID: 32403217
  231. Stewart, J.N.; Mounir, S.; Talbot, P.J. Human coronavirus gene expression in the brains of multiple sclerosis patients. Virology, 1992, 191(1), 502-505. doi: 10.1016/0042-6822(92)90220-J PMID: 1413524
  232. Antinori, A.; Arendt, G.; Becker, J.T.; Brew, B.J.; Byrd, D.A.; Cherner, M.; Clifford, D.B.; Cinque, P.; Epstein, L.G.; Goodkin, K.; Gisslen, M.; Grant, I.; Heaton, R.K.; Joseph, J.; Marder, K.; Marra, C.M.; McArthur, J.C.; Nunn, M.; Price, R.W.; Pulliam, L.; Robertson, K.R.; Sacktor, N.; Valcour, V.; Wojna, V.E. Updated research nosology for HIV-associated neurocognitive disorders. Neurology, 2007, 69(18), 1789-1799. doi: 10.1212/01.WNL.0000287431.88658.8b PMID: 17914061
  233. McArthur, J.C.; Brew, B.J. HIV-associated neurocognitive disorders: is there a hidden epidemic? AIDS, 2010, 24(9), 1367-1370. doi: 10.1097/QAD.0b013e3283391d56 PMID: 20559041
  234. McFarren, A.; Lopez, L.; Williams, D.W.; Veenstra, M.; Bryan, R.A.; Goldsmith, A.; Morgenstern, A.; Bruchertseifer, F.; Zolla-Pazner, S.; Gorny, M.K.; Eugenin, E.A.; Berman, J.W.; Dadachova, E. A fully human antibody to gp41 selectively eliminates HIV-infected cells that transmigrated across a model human blood brain barrier. AIDS, 2016, 30(4), 563-572. doi: 10.1097/QAD.0000000000000968 PMID: 26595540
  235. Persidsky, Y.; Hill, J.; Zhang, M.; Dykstra, H.; Winfield, M.; Reichenbach, N.L.; Potula, R.; Mukherjee, A.; Ramirez, S.H.; Rom, S. Dysfunction of brain pericytes in chronic neuroinflammation. J. Cereb. Blood Flow Metab., 2016, 36(4), 794-807. doi: 10.1177/0271678X15606149 PMID: 26661157
  236. Persidsky, Y.; Zheng, J.; Miller, D.; Gendelman, H.E. Mononuclear phagocytes mediate blood-brain barrier compromise and neuronal injury during HIV-1-associated dementia. J. Leukoc. Biol., 2000, 68(3), 413-422. doi: 10.1189/jlb.68.3.413 PMID: 10985259
  237. Solomon, T.; Patabendige, A.; Whitley, R.J. Arthropod-borne viral encephalititdes. In: Infections of the central nervous system; Scheld, WMW, J, R.; Marra, C.M., Eds.; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2014; pp. 210-238.
  238. Verma, S.; Lo, Y.; Chapagain, M.; Lum, S.; Kumar, M.; Gurjav, U.; Luo, H.; Nakatsuka, A.; Nerurkar, V.R. West Nile virus infection modulates human brain microvascular endothelial cells tight junction proteins and cell adhesion molecules: Transmigration across the in vitro blood-brain barrier. Virology, 2009, 385(2), 425-433. doi: 10.1016/j.virol.2008.11.047 PMID: 19135695
  239. Velandia-Romero, M.L.; Calderón-Peláez, M.A.; Castellanos, J.E. In vitro infection with dengue virus induces changes in the structure and function of the mouse brain endothelium. PLoS One, 2016, 11(6), e0157786. doi: 10.1371/journal.pone.0157786 PMID: 27336851
  240. Turtle, L.; Griffiths, M.J.; Solomon, T. Encephalitis caused by flaviviruses. QJM, 2012, 105(3), 219-223. doi: 10.1093/qjmed/hcs013 PMID: 22367423
  241. da Silva, I.R.F.; Frontera, J.A.; de Filippis, B.A.M.; Nascimento, O.J.M. Neurologic complications associated with the Zika virus in Brazilian adults. JAMA Neurol., 2017, 74(10), 1190-1198. doi: 10.1001/jamaneurol.2017.1703 PMID: 28806453
  242. Hoofnagle, J.H. Course and outcome of hepatitis C. Hepatology, 2002, 36(5), S21-S29. PMID: 12407573
  243. Farquhar, M.J.; McKeating, J.A. Primary hepatocytes as targets for Hepatitis C virus replication. J. Viral Hepat., 2008, 15(12), 849-854. doi: 10.1111/j.1365-2893.2008.01051.x PMID: 19087224
  244. Ploss, A.; Evans, M.J.; Gaysinskaya, V.A.; Panis, M.; You, H.; de Jong, Y.P.; Rice, C.M. Human occludin is a hepatitis C virus entry factor required for infection of mouse cells. Nature, 2009, 457(7231), 882-886. doi: 10.1038/nature07684 PMID: 19182773
  245. Fletcher, N.F.; Wilson, G.K.; Murray, J.; Hu, K.; Lewis, A.; Reynolds, G.M.; Stamataki, Z.; Meredith, L.W.; Rowe, I.A.; Luo, G.; Lopez-Ramirez, M.A.; Baumert, T.F.; Weksler, B.; Couraud, P.O.; Kim, K.S.; Romero, I.A.; Jopling, C.; Morgello, S.; Balfe, P.; McKeating, J.A. Hepatitis C virus infects the endothelial cells of the blood-brain barrier. Gastroenterology, 2012, 142(3), 634-643.e6. doi: 10.1053/j.gastro.2011.11.028 PMID: 22138189
  246. Untucht, C.; Rasch, J.; Fuchs, E.; Rohde, M.; Bergmann, S.; Steinert, M. An optimized in vitro blood-brain barrier model reveals bidirectional transmigration of African trypanosome strains. Microbiology, 2011, 157(10), 2933-2941. doi: 10.1099/mic.0.049106-0 PMID: 21737496
  247. Howland, S.W.; Poh, C.M.; Rénia, L. Activated brain endothelial eells cross- present malaria antigen. PLoS Pathog., 2015, 11(6), e1004963. doi: 10.1371/journal.ppat.1004963 PMID: 26046849
  248. Zougbédé, S.; Miller, F.; Ravassard, P.; Rebollo, A.; Cicéron, L.; Couraud, P.O.; Mazier, D.; Moreno, A. Metabolic acidosis induced by Plasmodium falciparum intraerythrocytic stages alters blood-brain barrier integrity. J. Cereb. Blood Flow Metab., 2011, 31(2), 514-526. doi: 10.1038/jcbfm.2010.121 PMID: 20683453
  249. Lachenmaier, S.M.; Deli, M.A.; Meissner, M.; Liesenfeld, O. Intracellular transport of toxoplasma gondii through the blood-brain barrier. J. Neuroimmunol., 2011, 232(1-2), 119-130. doi: 10.1016/j.jneuroim.2010.10.029 PMID: 21106256
  250. Kanmogne, G.D.; Schall, K.; Leibhart, J.; Knipe, B.; Gendelman, H.E.; Persidsky, Y. HIV-1 gp120 compromises blood-brain barrier integrity and enhances monocyte migration across blood-brain barrier: Implication for viral neuropathogenesis. J. Cereb. Blood Flow Metab., 2007, 27(1), 123-134. doi: 10.1038/sj.jcbfm.9600330 PMID: 16685256
  251. Mahajan, S.D.; Aalinkeel, R.; Sykes, D.E.; Reynolds, J.L.; Bindukumar, B.; Adal, A.; Qi, M.; Toh, J.; Xu, G.; Prasad, P.N.; Schwartz, S.A. Methamphetamine alters blood brain barrier permeability via the modulation of tight junction expression: Implication for HIV-1 neuropathogenesis in the context of drug abuse. Brain Res., 2008, 1203, 133-148. doi: 10.1016/j.brainres.2008.01.093 PMID: 18329007
  252. Persidsky, Y.; Stins, M.; Way, D.; Witte, M.H.; Weinand, M.; Kim, K.S.; Bock, P.; Gendelman, H.E.; Fiala, M. A model for monocyte migration through the blood-brain barrier during HIV-1 encephalitis. J. Immunol., 1997, 158(7), 3499-3510. doi: 10.4049/jimmunol.158.7.3499 PMID: 9120312
  253. Rochfort, K.D.; Cummins, P.M. In vitro cell models of the human blood-brain barrier: Demonstrating the beneficial influence of shear stress on brain microvascular endothelial cell phenotype. In: Blood-Brain Barrier; Barichello, T., Ed.; Springer New York: New York, NY, 2019; pp. 71-98. doi: 10.1007/978-1-4939-8946-1_5
  254. Perel, P.; Roberts, I.; Sena, E.; Wheble, P.; Briscoe, C.; Sandercock, P.; Macleod, M.; Mignini, L.E.; Jayaram, P.; Khan, K.S. Comparison of treatment effects between animal experiments and clinical trials: systematic review. BMJ, 2007, 334(7586), 197-200. doi: 10.1136/bmj.39048.407928.BE PMID: 17175568
  255. Wasielewska, J.M.; Da, J.C.; Chaves, S.; White, A.R.; Oikari, L.E. To understand drug delivery in Alzheimer’s disease. Alzheimer’s disease: drug discovery; Huang, X., Ed.; Exon Publications: Brisbane (AU), 2020, pp. 117-134. doi: 10.36255/exonpublications.alzheimersdisease.2020.ch7
  256. Brown, J.A.; Faley, S.L.; Shi, Y.; Hillgren, K.M.; Sawada, G.A.; Baker, T.K.; Wikswo, J.P.; Lippmann, E.S. Advances in blood-brain barrier modeling in microphysiological systems highlight critical differences in opioid transport due to cortisol exposure. Fluids Barriers CNS, 2020, 17(1), 38. doi: 10.1186/s12987-020-00200-9 PMID: 32493346
  257. Summerfield, S.G.; Lucas, A.J.; Porter, R.A.; Jeffrey, P.; Gunn, R.N.; Read, K.R.; Stevens, A.J.; Metcalf, A.C.; Osuna, M.C.; Kilford, P.J.; Passchier, J.; Ruffo, A.D. Toward an improved prediction of human in vivo brain penetration. Xenobiotica, 2008, 38(12), 1518-1535. doi: 10.1080/00498250802499459 PMID: 18979396
  258. Lacombe, O.; Videau, O.; Chevillon, D.; Guyot, A.C.; Contreras, C.; Blondel, S.; Nicolas, L.; Ghettas, A.; Bénech, H.; Thevenot, E.; Pruvost, A.; Bolze, S.; Krzaczkowski, L.; Prévost, C.; Mabondzo, A. In vitro primary human and animal cell-based blood-brain barrier models as a screening tool in drug discovery. Mol. Pharm., 2011, 8(3), 651-663. doi: 10.1021/mp1004614 PMID: 21438632
  259. Drummond, E.; Wisniewski, T. Alzheimer’s disease: Experimental models and reality. Acta Neuropathol., 2017, 133(2), 155-175. doi: 10.1007/s00401-016-1662-x PMID: 28025715
  260. Breschi, A.; Gingeras, T.R.; Guigó, R. Comparative transcriptomics in human and mouse. Nat. Rev. Genet., 2017, 18(7), 425-440. doi: 10.1038/nrg.2017.19 PMID: 28479595
  261. Nguyen, T.V.V.; Frye, J.B.; Zbesko, J.C.; Stepanovic, K.; Hayes, M.; Urzua, A.; Serrano, G.; Beach, T.G.; Doyle, K.P. Multiplex immunoassay characterization and species comparison of inflammation in acute and non-acute ischemic infarcts in human and mouse brain tissue. Acta Neuropathol. Commun., 2016, 4(1), 100. doi: 10.1186/s40478-016-0371-y PMID: 27600707
  262. Wang, M.M.; Zhang, X.; Lee, S.J.; Maripudi, S.; Keep, R.F.; Johnson, A.M.; Stamatovic, S.M.; Andjelkovic, A.V. Expression of periaxin (PRX) specifically in the human cerebrovascular system: PDZ domain-mediated strengthening of endothelial barrier function. Sci. Rep., 2018, 8(1), 10042. doi: 10.1038/s41598-018-28190-7 PMID: 29968755
  263. Urich, E.; Lazic, S.E.; Molnos, J.; Wells, I.; Freskgård, P.O. Transcriptional profiling of human brain endothelial cells reveals key properties crucial for predictive in vitro blood-brain barrier models. PLoS One, 2012, 7(5), e38149. doi: 10.1371/journal.pone.0038149 PMID: 22675443
  264. Hoshi, Y.; Uchida, Y.; Tachikawa, M.; Inoue, T.; Ohtsuki, S.; Terasaki, T. Quantitative atlas of blood-brain barrier transporters, receptors, and tight junction proteins in rats and common marmoset. J. Pharm. Sci., 2013, 102(9), 3343-3355. doi: 10.1002/jps.23575 PMID: 23650139
  265. O’Brown, N.M.; Pfau, S.J.; Gu, C. Bridging barriers: A comparative look at the blood-brain barrier across organisms. Genes Dev., 2018, 32(7-8), 466-478. doi: 10.1101/gad.309823.117 PMID: 29692355
  266. Oberheim, N.A.; Wang, X.; Goldman, S.; Nedergaard, M. Astrocytic complexity distinguishes the human brain. Trends Neurosci., 2006, 29(10), 547-553. doi: 10.1016/j.tins.2006.08.004 PMID: 16938356
  267. Prashanth, A.; Donaghy, H.; Stoner, S.P.; Hudson, A.L.; Wheeler, H.R.; Diakos, C.I.; Howell, V.M.; Grau, G.E.; McKelvey, K.J. Are in vitro human blood-brain-tumor‐barriers suitable replacements for in vivo models of brain permeability for novel therapeutics? Cancers, 2021, 13(5), 955. doi: 10.3390/cancers13050955 PMID: 33668807
  268. Ito, R.; Umehara, K.; Suzuki, S.; Kitamura, K.; Nunoya, K.; Yamaura, Y.; Imawaka, H.; Izumi, S.; Wakayama, N.; Komori, T.; Anzai, N.; Akita, H.; Furihata, T. A human immortalized cell-based blood-brain barrier triculture model: Development and characterization as a promising tool for drug-brain permeability studies. Mol. Pharm., 2019, 16(11), 4461-4471. doi: 10.1021/acs.molpharmaceut.9b00519 PMID: 31573814
  269. Cioni, C.; Turlizzi, E.; Zanelli, U.; Oliveri, G.; Annunziata, P. Expression of tight junction and drug efflux transporter proteins in an in vitro model of human blood-brain barrier. Front. Psychiatry, 2012, 3, 47. doi: 10.3389/fpsyt.2012.00047 PMID: 22593745

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