Abstract
As the blood-brain barrier (BBB) is essential for maintaining brain homeostasis and protecting the brain from exogenous substances, impermeability of the BBB is a major obstacle for drug delivery into the brain. Under pathological conditions, the integrity of the BBB is susceptible to disruption and can be broken down in severe brain diseases. Therefore, the understanding of intrinsic complexity as well as modulation of the BBB is critical to discover potential therapeutics for the treatment of brain diseases. Zebrafish (Danio rerio) have emerged as a suitable animal model in studying pathology of diseases and screening leading compounds in the drug development and discovery because of their highly conserved nature in both genetics and cell biology as higher vertebrates. Importantly, due to their small body size, ease of care, rapid development, and transparency in the early embryo stage, zebrafish allow researchers to study the BBB and carry out high-throughput screening of potential therapeutics with cost-effectiveness. We thus aim to provide a technical overview of the procedures that can be used to analyze BBB integrity and functionality in zebrafish. Low permeability and strong tight junction-based BBB in zebrafish are very similar to those of higher vertebrates. Zebrafish could be an excellent experimental model organism for studying the development and maintenance of the BBB, defining disease pathway, and discovering specific and powerful therapies for the treatment of brain diseases.
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References
Wilhelm I, Fazakas C, Krizbai IA (2011) In vitro models of the blood-brain barrier. Acta Neurobiol Exp (Wars) 71:113–128
De Rosa G, Salzano G, Caraglia M, Abbruzzese A (2012) Nanotechnologies: a strategy to overcome blood-brain barrier. Curr Drug Metab 13:61–69
Pardridge WM (2005) The blood-brain barrier: bottleneck in brain drug development. NeuroRx 2:3–14. https://doi.org/10.1602/neurorx.2.1.3
Pardridge WM (2007) Blood-brain barrier delivery. Drug Discov Today 12:54–61. https://doi.org/10.1016/j.drudis.2006.10.013
Nicolazzo JA, Charman SA, Charman WN (2006) Methods to assess drug permeability across the blood-brain barrier. J Pharm Pharmacol 58:281–293. https://doi.org/10.1211/jpp.58.3.0001
Reichel A, Begley DJ, Abbott NJ (2003) An overview of in vitro techniques for blood-brain barrier studies. Methods Mol Med 89:307–324. https://doi.org/10.1385/1-59259-419-0:307
Davis TP, Abbruscato TJ, Egleton RD (2015) Peptides at the blood brain barrier: knowing me knowing you. Peptides 72:50–56. https://doi.org/10.1016/j.peptides.2015.04.020
Keaney J, Campbell M (2015) The dynamic blood-brain barrier. FEBS J 282:4067–4079. https://doi.org/10.1111/febs.13412
Haseloff RF, Dithmer S, Winkler L, Wolburg H, Blasig IE (2015) Transmembrane proteins of the tight junctions at the blood-brain barrier: structural and functional aspects. Semin Cell Dev Biol 38:16–25. https://doi.org/10.1016/j.semcdb.2014.11.004
Kniesel U, Wolburg H (2000) Tight junctions of the blood-brain barrier. Cell Mol Neurobiol 20:57–76
Mahar Doan KM et al (2002) Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther 303:1029–1037. https://doi.org/10.1124/jpet.102.039255
Mahringer A, Ott M, Reimold I, Reichel V, Fricker G (2011) The ABC of the blood-brain barrier - regulation of drug efflux pumps. Curr Pharm Des 17:2762–2770
Rubinstein AL (2003) Zebrafish: from disease modeling to drug discovery. Curr Opin Drug Discov Devel 6:218–223
Lieschke GJ, Currie PD (2007) Animal models of human disease: zebrafish swim into view. Nat Rev Genet 8:353–367. https://doi.org/10.1038/nrg2091
Umans RA, Taylor MR (2012) Zebrafish as a model to study drug transporters at the blood-brain barrier. Clin Pharmacol Ther 92:567–570. https://doi.org/10.1038/clpt.2012.168
Xie J, Farage E, Sugimoto M, Anand-Apte B (2010) A novel transgenic zebrafish model for blood-brain and blood-retinal barrier development. BMC Dev Biol 10:76. https://doi.org/10.1186/1471-213X-10-76
Santoriello C, Zon LI (2012) Hooked! Modeling human disease in zebrafish. J Clin Invest 122:2337–2343. https://doi.org/10.1172/JCI60434
Jeong JY et al (2008) Functional and developmental analysis of the blood-brain barrier in zebrafish. Brain Res Bull 75:619–628. https://doi.org/10.1016/j.brainresbull.2007.10.043
Chakraborty C, Hsu CH, Wen ZH, Lin CS, Agoramoorthy G (2009) Zebrafish: a complete animal model for in vivo drug discovery and development. Curr Drug Metab 10:116–124
Karlsson J, von Hofsten J, Olsson PE (2001) Generating transparent zebrafish: a refined method to improve detection of gene expression during embryonic development. Mar Biotechnol (NY) 3:522–527. https://doi.org/10.1007/s1012601-0053-4
Avdesh A et al (2012) Regular care and maintenance of a zebrafish (Danio rerio) laboratory: an introduction. J Vis Exp e4196. https://doi.org/10.3791/4196
Sive HL, Grainger RM, Harland RM (2010) Calibration of the injection volume for microinjection of Xenopus oocytes and embryos. Cold Spring Harb Protoc 2010:pdb prot5537. https://doi.org/10.1101/pdb.prot5537
Eliceiri BP, Gonzalez AM, Baird A (2011) Zebrafish model of the blood-brain barrier: morphological and permeability studies. Methods Mol Biol 686:371–378. https://doi.org/10.1007/978-1-60761-938-3_18
Yang T et al (2015) Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio. Pharm Res 32:2003–2014. https://doi.org/10.1007/s11095-014-1593-y
Yang T et al (2017) Delivery of small interfering RNA to inhibit vascular endothelial growth factor in zebrafish using natural brain endothelia cell-secreted exosome nanovesicles for the treatment of brain cancer. AAPS J 19:475–486. https://doi.org/10.1208/s12248-016-0015-y
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Yang, T., Bai, S. (2019). Zebrafish (Danio rerio) as a Viable Model to Study the Blood-Brain Barrier. In: Barichello, T. (eds) Blood-Brain Barrier. Neuromethods, vol 142. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8946-1_11
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DOI: https://doi.org/10.1007/978-1-4939-8946-1_11
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