{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T01:28:16Z","timestamp":1791250096853,"version":"4.1.0"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T00:00:00Z","timestamp":1528416000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T00:00:00Z","timestamp":1528416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Blood brain barrier (BBB) cells play key roles in the physiology and pathology of the central nervous system (CNS). BBB dysfunction is implicated in many neurodegenerative diseases, including Alzheimer\u2019s disease (AD). The BBB consists of capillary endothelial cells, pericytes encircling the endothelium and surrounding astrocytes extending their processes towards it. Although there have been many attempts to develop<jats:italic>in vitro<\/jats:italic>BBB models, the complex interaction between these cell types makes it extremely difficult to determine their individual contribution to neurotoxicity<jats:italic>in vivo<\/jats:italic>. Thus, we developed and optimised an<jats:italic>in vitro<\/jats:italic>multicellular co-culture model within the Kirkstall Quasi Vivo System. The main aim was to determine the optimal environment to culture human brain primary endothelial cells, pericytes and astrocytes whilst maintaining cellular communication without formation of a barrier in order to assess the contribution of each cell type to the overall response. As a proof of concept for the present system, the effects of amyloid-beta 25-35 peptide (A\u03b225-35), a hallmark of AD, were explored. This multicellular system will be a valuable tool for future studies on the specific roles of individual BBB cell type (while making connection with each other through medium) in CNS disorders as well as in cytotoxicity tests.<\/jats:p>","DOI":"10.1038\/s41598-018-26480-8","type":"journal-article","created":{"date-parts":[[2018,6,4]],"date-time":"2018-06-04T11:17:20Z","timestamp":1528111040000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["A novel dynamic multicellular co-culture system for studying individual blood-brain barrier cell types in brain diseases and cytotoxicity testing"],"prefix":"10.1038","volume":"8","author":[{"given":"Patricia","family":"Miranda-Azpiazu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavros","family":"Panagiotou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gin","family":"Jose","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sikha","family":"Saha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,6,8]]},"reference":[{"key":"26480_CR1","first-page":"1035","volume":"67","author":"Y Takeshita","year":"2015","unstructured":"Takeshita, Y. & Kanda, T. The Blood-Brain Barrier (BBB) and in vitro BBB Models. Brain Nerve Aug. 67, 1035\u20131042 (2015).","journal-title":"Brain Nerve Aug."},{"key":"26480_CR2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/0471142301.ns0327s69","volume":"69","author":"A Patabendige","year":"2014","unstructured":"Patabendige, A. & Abbott, N. J. Primary porcine brain microvessel endothelial cell isolation and culture. Curr Protoc Neurosci 69, 1\u20133 (2014).","journal-title":"Curr Protoc Neurosci"},{"key":"26480_CR3","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1046\/j.1469-7580.2002.00064.x","volume":"200","author":"NJ Abbott","year":"2002","unstructured":"Abbott, N. J. Astrocyte-endothelial interactions and blood-brain barrier permeability. J Anat 200, 629\u2013638 (2002).","journal-title":"J Anat"},{"key":"26480_CR4","doi-asserted-by":"publisher","first-page":"e0124362","DOI":"10.1371\/journal.pone.0124362","volume":"10","author":"Y Bai","year":"2015","unstructured":"Bai, Y. et al. Pericytes contribute to the disruption of the cerebral endothelial barrier via increasing VEGF expression: implications for stroke. PLoS One 10, e0124362 (2015).","journal-title":"PLoS One"},{"key":"26480_CR5","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.brainres.2014.10.047","volume":"1594","author":"P Candela","year":"2015","unstructured":"Candela, P. et al. In vitro discrimination of the role of LRP1 at the BBB cellular level: focus on brain capillary endothelial cells and brain pericytes. Brain Res 1594, 15\u201326 (2015).","journal-title":"Brain Res"},{"key":"26480_CR6","doi-asserted-by":"crossref","unstructured":"Gokcinar-Yagci, B., Uckan-Cetinkaya, D. & Celebi-Saltik, B. Pericytes: Properties, Functions and Applications in Tissue Engineering. Stem Cell Rev (2015).","DOI":"10.1007\/s12015-015-9590-z"},{"key":"26480_CR7","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.neuint.2008.12.002","volume":"54","author":"S Nakagawa","year":"2009","unstructured":"Nakagawa, S. et al. A new blood-brain barrier model using primary rat brain endothelial cells, pericytes and astrocytes. Neurochem Int 54, 253\u2013263 (2009).","journal-title":"Neurochem Int"},{"key":"26480_CR8","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/jcbfm.2010.148","volume":"31","author":"A Al Ahmad","year":"2011","unstructured":"Al Ahmad, A., Taboada, C. B., Gassmann, M. & Ogunshola, O. O. Astrocytes and pericytes differentially modulate blood-brain barrier characteristics during development and hypoxic insult. J Cereb Blood Flow Metab 31, 693\u2013705 (2011).","journal-title":"J Cereb Blood Flow Metab"},{"key":"26480_CR9","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/nature09522","volume":"468","author":"A Armulik","year":"2010","unstructured":"Armulik, A. et al. Pericytes regulate the blood-brain barrier. Nature 468, 557\u2013561 (2010).","journal-title":"Nature"},{"key":"26480_CR10","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/2045-8118-8-8","volume":"8","author":"D Bonkowski","year":"2011","unstructured":"Bonkowski, D., Katyshev, V., Balabanov, R. D., Borisov, A. & Dore-Duffy, P. The CNS microvascular pericyte: pericyte-astrocyte crosstalk in the regulation of tissue survival. Fluids Barriers CNS 8, 8\u201381 (2011).","journal-title":"Fluids Barriers CNS"},{"key":"26480_CR11","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1038\/nature09513","volume":"468","author":"R Daneman","year":"2010","unstructured":"Daneman, R., Zhou, L., Kebede, A. A. & Barres, B. A. Pericytes are required for blood-brain barrier integrity during embryogenesis. Nature 468, 562\u2013566 (2010).","journal-title":"Nature"},{"key":"26480_CR12","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.2174\/138161208784705469","volume":"14","author":"P Dore-Duffy","year":"2008","unstructured":"Dore-Duffy, P. Pericytes: pluripotent cells of the blood brain barrier. Curr Pharm Des 14, 1581\u20131593 (2008).","journal-title":"Curr Pharm Des"},{"key":"26480_CR13","doi-asserted-by":"publisher","DOI":"10.1038\/srep36450","volume":"6","author":"J Gautam","year":"2016","unstructured":"Gautam, J., Zhang, X. & Yao, Y. The role of pericytic laminin in blood brain barrier integrity maintenance. Sci Rep 6, 36450 (2016).","journal-title":"Sci Rep"},{"key":"26480_CR14","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1083\/jcb.153.3.543","volume":"153","author":"M Hellstrom","year":"2001","unstructured":"Hellstrom, M. et al. Lack of pericytes leads to endothelial hyperplasia and abnormal vascular morphogenesis. J Cell Biol 153, 543\u2013553 (2001).","journal-title":"J Cell Biol"},{"key":"26480_CR15","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/978-1-61779-452-0_31","volume":"814","author":"V Katyshev","year":"2012","unstructured":"Katyshev, V. & Dore-Duffy, P. Pericyte coculture models to study astrocyte, pericyte, and endothelial cell interactions. Methods Mol Biol 814, 467\u2013481 (2012).","journal-title":"Methods Mol Biol"},{"key":"26480_CR16","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1007\/s10571-007-9195-4","volume":"27","author":"S Nakagawa","year":"2007","unstructured":"Nakagawa, S. et al. Pericytes from brain microvessels strengthen the barrier integrity in primary cultures of rat brain endothelial cells. Cell Mol Neurobiol 27, 687\u2013694 (2007).","journal-title":"Cell Mol Neurobiol"},{"key":"26480_CR17","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1038\/nn.4288","volume":"19","author":"MD Sweeney","year":"2016","unstructured":"Sweeney, M. D., Ayyadurai, S. & Zlokovic, B. V. Pericytes of the neurovascular unit: key functions and signaling pathways. Nat Neurosci 19, 771\u2013783 (2016).","journal-title":"Nat Neurosci"},{"key":"26480_CR18","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1471-2202-14-18","volume":"14","author":"L Cucullo","year":"2013","unstructured":"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 14, 14\u201318 (2013).","journal-title":"BMC Neurosci"},{"key":"26480_CR19","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/978-1-61779-452-0_28","volume":"814","author":"NJ Abbott","year":"2012","unstructured":"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. Methods Mol Biol 814, 415\u2013430 (2012).","journal-title":"Methods Mol Biol"},{"key":"26480_CR20","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/0165-3806(87)90075-7","volume":"433","author":"FE Arthur","year":"1987","unstructured":"Arthur, F. E., Shivers, R. R. & Bowman, P. D. Astrocyte-mediated induction of tight junctions in brain capillary endothelium: an efficient in vitro model. Brain Res 433, 155\u2013159 (1987).","journal-title":"Brain Res"},{"key":"26480_CR21","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1097\/00005072-198405000-00001","volume":"43","author":"DW Beck","year":"1984","unstructured":"Beck, D. W., Vinters, H. V., Hart, M. N. & Cancilla, P. A. Glial cells influence polarity of the blood-brain barrier. J Neuropathol Exp Neurol 43, 219\u2013224 (1984).","journal-title":"J Neuropathol Exp Neurol"},{"key":"26480_CR22","doi-asserted-by":"publisher","first-page":"054124","DOI":"10.1063\/1.4934713","volume":"9","author":"JA Brown","year":"2015","unstructured":"Brown, J. A. et al. Recreating blood-brain barrier physiology and structure on chip: A novel neurovascular microfluidic bioreactor. Biomicrofluidics 9, 054124 (2015).","journal-title":"Biomicrofluidics"},{"key":"26480_CR23","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/S0006-8993(02)03167-0","volume":"951","author":"L Cucullo","year":"2002","unstructured":"Cucullo, L. et al. A new dynamic in vitro model for the multidimensional study of astrocyte-endothelial cell interactions at the blood-brain barrier. Brain Res 951, 243\u2013254 (2002).","journal-title":"Brain Res"},{"key":"26480_CR24","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.brainres.2007.02.029","volume":"1147","author":"V Siddharthan","year":"2007","unstructured":"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 1147, 39\u201350 (2007).","journal-title":"Brain Res"},{"key":"26480_CR25","doi-asserted-by":"publisher","first-page":"e0134765","DOI":"10.1371\/journal.pone.0134765","volume":"10","author":"LB Thomsen","year":"2015","unstructured":"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 10, e0134765 (2015).","journal-title":"PLoS One"},{"key":"26480_CR26","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.12688\/f1000research.7142.1","volume":"4","author":"P Sreekanthreddy","year":"2015","unstructured":"Sreekanthreddy, P. et al. A three-dimensional model of the human blood-brain barrier to analyse the transport of nanoparticles and astrocyte\/endothelial interactions. F1000Res 4, 1279 (2015).","journal-title":"F1000Res"},{"key":"26480_CR27","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.colsurfb.2011.04.005","volume":"86","author":"YC Kuo","year":"2011","unstructured":"Kuo, Y. C. & Lu, C. H. Effect of human astrocytes on the characteristics of human brain-microvascular endothelial cells in the blood-brain barrier. Colloids Surf B Biointerfaces 86, 225\u2013231 (2011).","journal-title":"Colloids Surf B Biointerfaces"},{"key":"26480_CR28","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1038\/jcbfm.2013.135","volume":"33","author":"MA Erickson","year":"2013","unstructured":"Erickson, M. A. & Banks, W. A. Blood-brain barrier dysfunction as a cause and consequence of Alzheimer\u2019s disease. J Cereb Blood Flow Metab 33, 1500\u20131513 (2013).","journal-title":"J Cereb Blood Flow Metab"},{"key":"26480_CR29","first-page":"987","volume":"27","author":"F Gosselet","year":"2011","unstructured":"Gosselet, F., Candela, P., Cecchelli, R. & Fenart, L. Role of the blood-brain barrier in Alzheimer\u2019s disease. Med Sci 27, 987\u2013992 (2011).","journal-title":"Med Sci"},{"key":"26480_CR30","doi-asserted-by":"publisher","first-page":"54","DOI":"10.2174\/138920310790274626","volume":"11","author":"L Millucci","year":"2010","unstructured":"Millucci, L., Ghezzi, L., Bernardini, G. & Santucci, A. Conformations and biological activities of amyloid beta peptide 25-35. Curr Protein Pept Sci 11, 54\u201367 (2010).","journal-title":"Curr Protein Pept Sci"},{"key":"26480_CR31","doi-asserted-by":"crossref","unstructured":"C\u00e1rdenas-Aguayo, M. et al. Physiological Role of Amyloid Beta in Neural Cells: The Cellular Trophic Activity. Neurochemistry (2014).","DOI":"10.5772\/57398"},{"key":"26480_CR32","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1078\/0065-1281-00696","volume":"105","author":"IG Farkas","year":"2003","unstructured":"Farkas, I. G. et al. Beta-amyloid peptide-induced blood-brain barrier disruption facilitates T-cell entry into the rat brain. Acta Histochem 105, 115\u2013125 (2003).","journal-title":"Acta Histochem"},{"key":"26480_CR33","doi-asserted-by":"publisher","first-page":"548","DOI":"10.3390\/pr2030548","volume":"2","author":"G Mattei","year":"2014","unstructured":"Mattei, G., Giusti, S. & Ahluwalia, A. Design criteria for generating physiological relevant in vitro models in bioreactors. Processes 2, 548\u2013569 (2014).","journal-title":"Processes"},{"issue":"1","key":"26480_CR34","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1002\/bit.22671","volume":"106","author":"D Mazzei","year":"2010","unstructured":"Mazzei, D., Guzzardi, M. A., Giusti, S. & Ahluwalia, A. A low shear stress modular bioreactor for connected cell culture under high flow rates. Biotechnol Bioeng 106(1), 127\u2013137 (2010).","journal-title":"Biotechnol Bioeng"},{"key":"26480_CR35","doi-asserted-by":"publisher","first-page":"697","DOI":"10.3109\/17435390.2013.831500","volume":"6","author":"N Ucciferri","year":"2014","unstructured":"Ucciferri, N. et al. In vitro toxicological screening of nanoparticles on primary human endothelial cells and the role of flow in modulating cell respose. Nanotoxicology 6, 697\u2013708 (2014).","journal-title":"Nanotoxicology"},{"issue":"7","key":"26480_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/srep42113","volume":"7","author":"A Ahluwalia","year":"2017","unstructured":"Ahluwalia, A. Allometric scaling in vitro. Sci Rep 7(7), 42113 (2017).","journal-title":"Sci Rep"},{"issue":"6","key":"26480_CR37","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1002\/biot.201000009","volume":"5","author":"B Vinci","year":"2010","unstructured":"Vinci, B. et al. Flow-regulated glucose and lipid metabolism in adipose tissue, endothelial cell and hepatocyte cultures in a modular bioreactor. Biotechnol J 5(6), 618\u2013626 (2010).","journal-title":"Biotechnol J"},{"key":"26480_CR38","doi-asserted-by":"publisher","first-page":"13(2):e0192824","DOI":"10.1371\/journal.pone.0192824","volume":"13","author":"A Ahluwalia","year":"2018","unstructured":"Ahluwalia, A. et al. Systemic and vascular inflammation in an in vitro model of central obesity. PLoS One 13(2), e0192824 (2018).","journal-title":"PLoS One"},{"issue":"1","key":"26480_CR39","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1002\/biot.201100177","volume":"7","author":"B Vinci","year":"2012","unstructured":"Vinci, B. et al. An in vitro model of glucose and lipid metabolism in a multicompartmental bioreactor. Biotechnol J 7(1), 117\u2013126 (2012).","journal-title":"Biotechnol J"},{"key":"26480_CR40","doi-asserted-by":"publisher","unstructured":"Pedersen, J. M. et al. Fluid Dynamic Modeling to Support the Development of Flow-Based Hepatocyte Culture Systems for Metabolism Studies. Front.Bioengineer and Biotechnol 4: Article 72, 1\u201313, https:\/\/doi.org\/10.3389\/fbioe.2016.00072.","DOI":"10.3389\/fbioe.2016.00072"},{"key":"26480_CR41","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/j.neuint.2003.11.006","volume":"45","author":"NJ Abbott","year":"2004","unstructured":"Abbott, N. J. Evidence for bulk flow of brain interstitial fluid: significance for physiology and pathology. Neurochem Int 45, 545\u2013552 (2004).","journal-title":"Neurochem Int"},{"key":"26480_CR42","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/j.1750-3639.1992.tb00704.x","volume":"2","author":"RO Weller","year":"1992","unstructured":"Weller, R. O., Kida, S. & Zhang, E. T. Pathways of fluid drainage from the brain\u2013morphological aspects and immunological significance in rat and man. Brain Pathol 2, 277\u2013284 (1992).","journal-title":"Brain Pathol"},{"key":"26480_CR43","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.tins.2008.03.003","volume":"31","author":"NR Saunders","year":"2008","unstructured":"Saunders, N. R., Ek, C. J., Habgood, M. D. & Dziegielewska, K. M. Barriers in the brain: a renaissance? Trends Neurosci 31, 279\u2013286 (2008).","journal-title":"Trends Neurosci"},{"issue":"2011","key":"26480_CR44","doi-asserted-by":"crossref","first-page":"304583","DOI":"10.4061\/2011\/304583","volume":"12","author":"M Kawahara","year":"2011","unstructured":"Kawahara, M., Ohtsuka, I., Yokoyama, S., Kato-Negishi, M. & Sadakane, Y. Membrane Incorporation, Channel Formation, and Disruption of Calcium Homeostasis by Alzheimer\u2019s beta-Amyloid Protein. Int J Alzheimers Dis 12(2011), 304583 (2011).","journal-title":"Int J Alzheimers Dis"},{"issue":"3","key":"26480_CR45","doi-asserted-by":"publisher","first-page":"689","DOI":"10.3233\/JAD-150896","volume":"51","author":"C Peters","year":"2016","unstructured":"Peters, C., Bascunan, D., Opazo, C. & Aguayo, L. G. Differential Membrane Toxicity of Amyloid-beta Fragments by Pore Forming Mechanisms. J Alzheimers Dis 51(3), 689\u2013699 (2016).","journal-title":"J Alzheimers Dis"},{"key":"26480_CR46","first-page":"20658","volume":"15","author":"W Chang","year":"2015","unstructured":"Chang, W. & Teng, J. beta-asarone prevents Abeta25-35-induced inflammatory responses and autophagy in SH-SY5Y cells: down expression Beclin-1, LC3B and up expression Bcl-2. Int J Clin Exp Med 15, 20658\u201320663 (2015).","journal-title":"Int J Clin Exp Med"},{"key":"26480_CR47","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1089\/jmf.2014.3150","volume":"18","author":"W Ma","year":"2015","unstructured":"Ma, W. et al. Genistein alleviates beta-amyloid-induced inflammatory damage through regulating Toll-like receptor 4\/nuclear factor kappaB. J Med Food 18, 273\u2013279 (2015).","journal-title":"J Med Food"},{"key":"26480_CR48","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1046\/j.1471-4159.1997.68031135.x","volume":"68","author":"MM Verbeek","year":"1997","unstructured":"Verbeek, M. M., de Waal, R. M., Schipper, J. J. & Van Nostrand, W. E. Rapid degeneration of cultured human brain pericytes by amyloid beta protein. J Neurochem 68, 1135\u20131141 (1997).","journal-title":"J Neurochem"},{"key":"26480_CR49","first-page":"37","volume":"45","author":"MM Verbeek","year":"1999","unstructured":"Verbeek, M. M., Otte-Holler, I., Ruiter, D. J. & de Waal, R. M. Human brain pericytes as a model system to study the pathogenesis of cerebrovascular amyloidosis in Alzheimer\u2019s disease. Cell Mol Biol 45, 37\u201346 (1999).","journal-title":"Cell Mol Biol"},{"key":"26480_CR50","doi-asserted-by":"crossref","unstructured":"Lazcano, Z. et al. Unilateral injection of A\u03b225-35 in the hippocampus reduces the number of dendritic spines in hyperglycemic rats. Synapse 22 (2014).","DOI":"10.1002\/syn.21770"},{"key":"26480_CR51","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.ejphar.2013.02.015","volume":"15","author":"YW Lee","year":"2013","unstructured":"Lee, Y. W. et al. Neuroprotective effects of salvianolic acid B on an A\u03b225-35 peptide-induced mouse model of Alzheimer\u2019s disease. Eur J Pharmacol 15, 70\u201377 (2013).","journal-title":"Eur J Pharmacol"},{"key":"26480_CR52","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.etp.2016.02.001","volume":"68","author":"F Lattanzio","year":"2016","unstructured":"Lattanzio, F., Carboni, L., Carretta, D., Candeletti, S. & Romualdi, P. Treatment with the neurotoxic Abeta (25-35) peptide modulates the expression of neuroprotective factors Pin1, Sirtuin 1, and brain-derived neurotrophic factor in SH-SY5Y human neuroblastoma cells. Exp Toxicol Pathol 68, 271\u2013276 (2016).","journal-title":"Exp Toxicol Pathol"},{"key":"26480_CR53","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1039\/b612140c","volume":"6","author":"MW Toepke","year":"2006","unstructured":"Toepke, M. W. & Beebe, D. J. PDMS absorption of small molecules and consequences in microfluidic applications. Lab Chip, The Royal Society of Chemistry 6, 1484\u20131486, https:\/\/doi.org\/10.1039\/b612140c (2006).","journal-title":"Lab Chip, The Royal Society of Chemistry"},{"issue":"11","key":"26480_CR54","doi-asserted-by":"publisher","first-page":"1391","DOI":"10.1039\/b926849a","volume":"10","author":"Q Han","year":"2010","unstructured":"Han, Q., Bradshaw, E. M., Nilsson, B. & Hafler, D. A. Love JC. Multidimensional analysis of the frequencies and rates of cytokine secretion from single cells by quantitative microengraving. Lab Chip 10(11), 1391\u20131400 (2010).","journal-title":"Lab Chip"},{"issue":"22","key":"26480_CR55","doi-asserted-by":"publisher","first-page":"13165","DOI":"10.1073\/pnas.95.22.13165","volume":"95","author":"A Whitty","year":"1998","unstructured":"Whitty, A. et al. Interaction affinity between cytokine receptor components on the cell surface. Proc Natl Acad Sci 95(22), 13165\u201313170 (1998).","journal-title":"Proc Natl Acad Sci"},{"key":"26480_CR56","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1177\/0271678X16630991","volume":"36","author":"HC Helms","year":"2016","unstructured":"Helms, H. C. et al. In vitro models of the blood-brain barrier: An overview of commonly used brain endothelial cell culture models and guidelines for their use. J Cereb Blood Flow Metab 36, 862\u2013890 (2016).","journal-title":"J Cereb Blood Flow Metab"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-26480-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-26480-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-26480-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,7]],"date-time":"2024-07-07T07:39:24Z","timestamp":1720337964000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-018-26480-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,8]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2018,12]]}},"alternative-id":["26480"],"URL":"https:\/\/doi.org\/10.1038\/s41598-018-26480-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,8]]},"assertion":[{"value":"10 October 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 May 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"8784"}}