{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T20:38:52Z","timestamp":1776458332071,"version":"3.51.2"},"reference-count":187,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["DL57\/2016\/CP1355\/CT0007"],"award-info":[{"award-number":["DL57\/2016\/CP1355\/CT0007"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["DL57\/2016\/CP1355\/CT0007"],"award-info":[{"award-number":["DL57\/2016\/CP1355\/CT0007"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["DL57\/2016\/CP1355\/CT0007"],"award-info":[{"award-number":["DL57\/2016\/CP1355\/CT0007"]}]},{"name":"FCT Junior Researcher position","award":["UIDP\/04378\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020"]}]},{"name":"FCT Junior Researcher position","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]},{"name":"FCT Junior Researcher position","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"FCT Junior Researcher position","award":["DL57\/2016\/CP1355\/CT0007"],"award-info":[{"award-number":["DL57\/2016\/CP1355\/CT0007"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomedicines"],"abstract":"<jats:p>The biological barriers existing in the human body separate the blood circulation from the interstitial fluid in tissues. The blood\u2013brain barrier (BBB) isolates the central nervous system from the bloodstream, presenting a dual role: the protection of the human brain against potentially toxic\/harmful substances coming from the blood, while providing nutrients to the brain and removing metabolites. In terms of architectural features, the presence of junctional proteins (that restrict the paracellular transport) and the existence of efflux transporters at the BBB are the two major in vivo characteristics that increase the difficulty in creating an ideal in vitro model for drug permeability studies and neurotoxicity assessments. The purpose of this work is to provide an up-to-date literature review on the current in vitro models used for BBB studies, focusing on the characteristics, advantages, and disadvantages of both primary cultures and immortalized cell lines. An accurate analysis of the more recent and emerging techniques implemented to optimize the in vitro models is also provided, based on the need of recreating as closely as possible the BBB microenvironment. In fact, the acceptance that the BBB phenotype is much more than endothelial cells in a monolayer has led to the shift from single-cell to multicellular models. Thus, in vitro co-culture models have narrowed the gap between recreating as faithfully as possible the human BBB phenotype. This is relevant for permeability and neurotoxicity assays, and for studies related to neurodegenerative diseases. Several studies with these purposes will be also presented and discussed.<\/jats:p>","DOI":"10.3390\/biomedicines12030626","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T12:17:16Z","timestamp":1710245836000},"page":"626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Co-Culture Models: Key Players in In Vitro Neurotoxicity, Neurodegeneration and BBB Modeling Studies"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3132-8669","authenticated-orcid":false,"given":"Ana Rita","family":"Monteiro","sequence":"first","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, Porto University, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1726-6011","authenticated-orcid":false,"given":"Daniel Jos\u00e9","family":"Barbosa","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), 4585-116 Gandra, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, University Institute of Health Sciences\u2014CESPU, 4585-116 Gandra, Portugal"},{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1382-5119","authenticated-orcid":false,"given":"Fernando","family":"Remi\u00e3o","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, Porto University, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9962-7548","authenticated-orcid":false,"given":"Renata","family":"Silva","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, Porto University, 4050-313 Porto, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/2045-8118-10-2","article-title":"Modeling the Blood-Brain Barrier Using Stem Cell Sources","volume":"10","author":"Lippmann","year":"2013","journal-title":"Fluids Barriers CNS"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Barichello, T., Collodel, A., Hasbun, R., and Morales, R. (2019). An Overview of the Blood-Brain Barrier, Humana Press.","DOI":"10.1007\/978-1-4939-8946-1_1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1021\/mp500046f","article-title":"In Vitro Models of the Blood-Brain Barrier for the Study of Drug Delivery to the Brain","volume":"11","author":"Wilhelm","year":"2014","journal-title":"Mol. Pharm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4067","DOI":"10.1111\/febs.13412","article-title":"The Dynamic Blood-Brain Barrier","volume":"282","author":"Keaney","year":"2015","journal-title":"FEBS J."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1007\/s00018-014-1625-0","article-title":"Developmental and Pathological Angiogenesis in the Central Nervous System","volume":"71","author":"Vallon","year":"2014","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s00441-014-1811-2","article-title":"Novel Insights into the Development and Maintenance of the Blood-Brain Barrier","volume":"355","author":"Engelhardt","year":"2014","journal-title":"Cell Tissue Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.placenta.2016.12.005","article-title":"Review: The Blood-Brain Barrier; Protecting the Developing Fetal Brain","volume":"54","author":"Miller","year":"2017","journal-title":"Placenta"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/nm.3407","article-title":"Development, Maintenance and Disruption of the Blood-Brain Barrier","volume":"19","author":"Obermeier","year":"2013","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00401-018-1815-1","article-title":"Functional Morphology of the Blood\u2013Brain Barrier in Health and Disease","volume":"135","author":"Liebner","year":"2018","journal-title":"Acta Neuropathol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Costea, L., Bauer, H., Bauer, H.C., Traweger, A., Wilhelm, I., Farkas, A.E., and Krizbai, I.A. (2019). The Blood\u2013Brain Barrier and Its Intercellular Junctions in Age-Related Brain Disorders. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215472"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fneng.2013.00007","article-title":"The Blood-Brain Barrier: An Engineering Perspective","volume":"6","author":"Wong","year":"2013","journal-title":"Front. Neuroeng."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"196","DOI":"10.3389\/fnagi.2019.00196","article-title":"Age-Related Functional and Expressional Changes in Efflux Pathways at the Blood\u2013Brain Barrier","volume":"10","author":"Erdo","year":"2019","journal-title":"Front. Aging Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jackson, S., Meeks, C., V\u00e9zina, A., Robey, R.W., Tanner, K., and Gottesman, M.M. (2019). Model Systems for Studying the Blood-Brain Barrier: Applications and Challenges. Biomaterials, 214.","DOI":"10.1016\/j.biomaterials.2019.05.028"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nbd.2003.12.016","article-title":"The Blood-Brain Barrier: An Overview: Structure, Regulation, and Clinical Implications","volume":"16","author":"Ballabh","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1083\/jcb.201412147","article-title":"Brain Barriers: Crosstalk between Complex Tight Junctions and Adherens Junctions","volume":"209","author":"Tietz","year":"2015","journal-title":"J. Cell Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.yexcr.2017.03.061","article-title":"Interplay between Tight Junctions & Adherens Junctions","volume":"358","author":"Campbell","year":"2017","journal-title":"Exp. Cell Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12987-018-0097-2","article-title":"Brain Vascular Heterogeneity: Implications for Disease Pathogenesis and Design of in Vitro Blood-Brain Barrier Models","volume":"15","author":"Noumbissi","year":"2018","journal-title":"Fluids Barriers CNS"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.cobme.2017.11.002","article-title":"Modeling the Blood\u2013Brain Barrier: Beyond the Endothelial Cells","volume":"5","author":"Gastfriend","year":"2018","journal-title":"Curr. Opin. Biomed. Eng."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1007\/s11481-006-9025-3","article-title":"Blood-Brain Barrier: Structural Components and Function under Physiologic and Pathologic Conditions","volume":"1","author":"Persidsky","year":"2006","journal-title":"J. Neuroimmune Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2514","DOI":"10.1161\/STROKEAHA.114.005427","article-title":"Cell-Culture Models of the Blood-Brain Barrier","volume":"45","author":"He","year":"2014","journal-title":"Stroke"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/clpt.2013.34","article-title":"Why Clinical Modulation of Efflux Transport at the Human Blood-Brain Barrier Is Unlikely: The ITC Evidence-Based Position","volume":"94","author":"Kalvass","year":"2013","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.brainres.2015.07.005","article-title":"Regulation of ABC Efflux Transporters at Blood-Brain Barrier in Health and Neurological Disorders","volume":"1628","author":"Qosa","year":"2015","journal-title":"Brain Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"107554","DOI":"10.1016\/j.pharmthera.2020.107554","article-title":"Dysfunction of ABC Transporters at the Blood-Brain Barrier: Role in Neurological Disorders","volume":"213","author":"Barbosa","year":"2020","journal-title":"Pharmacol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2014.11.013","article-title":"Modulation of P-Glycoprotein Efflux Pump: Induction and Activation as a Therapeutic Strategy","volume":"149","author":"Silva","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Gameiro, M., Silva, R., Rocha-Pereira, C., Carmo, H., Carvalho, F., Bastos, M.D.L., and Remi\u00e3o, F. (2017). Cellular Models and in Vitro Assays for the Screening of Modulators of P-Gp, MRP1 and BCRP. Molecules, 22.","DOI":"10.3390\/molecules22040600"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gomez-Zepeda, D., Taghi, M., Scherrmann, J.M., Decleves, X., and Menet, M.C. (2020). ABC Transporters at the Blood\u2013Brain Interfaces, Their Study Models, and Drug Delivery Implications in Gliomas. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12010020"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1007\/s11064-016-2030-x","article-title":"Solute Carriers in the Blood\u2013Brain Barier: Safety in Abundance","volume":"42","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"215","DOI":"10.7600\/jpfsm.6.215","article-title":"Creatine in the Brain","volume":"6","author":"Kurosawa","year":"2017","journal-title":"J. Phys. Fit. Sports Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1177\/0271678X16630991","article-title":"In Vitro Models of the Blood-Brain Barrier: An Overview of Commonly Used Brain Endothelial Cell Culture Models and Guidelines for Their Use","volume":"36","author":"Helms","year":"2015","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12987-018-0117-2","article-title":"Benchmarking in Vitro Tissue\u2014Engineered Blood-Brain Barrier Models","volume":"15","author":"Destefano","year":"2018","journal-title":"Fluids Barriers CNS"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1007\/s00702-020-02202-1","article-title":"Comparison of the Rate of Dedifferentiation with Increasing Passages among Cell Sources for an in Vitro Model of the Blood\u2013Brain Barrier","volume":"127","author":"Fujimoto","year":"2020","journal-title":"J. Neural Transm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113","DOI":"10.55782\/ane-2011-1828","article-title":"In Vitro Models of the Blood-Brain Barrier","volume":"71","author":"Wilhelm","year":"2011","journal-title":"Acta Neurobiol. Exp."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.2147\/DDDT.S218708","article-title":"In-Vitro Blood-Brain Barrier Models for Drug Screening and Permeation Studies: An Overview","volume":"13","author":"Design","year":"2019","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1016\/S1359-6446(03)02858-7","article-title":"New Approaches to in Vitro Models of Blood-Brain Barrier Drug Transport","volume":"8","author":"Terasaki","year":"2003","journal-title":"Drug Discov. Today"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/2045-8118-10-33","article-title":"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 Comparative Stu","volume":"10","author":"Eigenmann","year":"2013","journal-title":"Fluids Barriers CNS"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1111\/j.1471-4159.1989.tb08526.x","article-title":"Bovine Brain Endothelial Cells Express Tight Junctions and Monoamine Oxidase Activity in Long-Term Culture","volume":"53","author":"Dehouck","year":"1989","journal-title":"J. Neurochem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1002\/jps.23146","article-title":"Molecular Nanomedicine Towards Cancer","volume":"101","author":"Psimadas","year":"2012","journal-title":"J. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/S0731-7085(01)00542-8","article-title":"Comparison of in Vitro BBMEC Permeability and in Vivo CNS Uptake by Microdialysis Sampling","volume":"27","author":"Hansen","year":"2002","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E531","DOI":"10.1152\/ajpendo.00350.2016","article-title":"The Insulin Receptor Is Expressed and Functional in Cultured Blood-Brain Barrier Endothelial Cells but Does Not Mediate Insulin Entry from Blood to Brain","volume":"315","author":"Hersom","year":"2018","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_40","first-page":"369","article-title":"Carrier-Mediated Transport of Baclofen Across Monolayers of Bovine Brain Endothelial Cells in Primary Culture","volume":"5","author":"Audus","year":"1988","journal-title":"Pharm. Res. Off. J. Am. Assoc. Pharm. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.tiv.2007.12.016","article-title":"An in Vitro Blood-Brain Barrier Model for High Throughput (HTS) Toxicological Screening","volume":"22","author":"Culot","year":"2008","journal-title":"Toxicol. Vitr."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Freese, C., Reinhardt, S., Hefner, G., Unger, R.E., Kirkpatrick, C.J., and Endres, K. (2014). A Novel Blood-Brain Barrier Co-Culture System for Drug Targeting of Alzheimer\u2019s Disease: Establishment by Using Acitretin as a Model Drug. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0091003"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1080\/10611860701288539","article-title":"Primary Porcine Brain Microvascular Endothelial Cells: Biochemical and Functional Characterisation as a Model for Drug Transport and Targeting","volume":"15","author":"Smith","year":"2007","journal-title":"J. Drug Target."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.brainres.2013.04.006","article-title":"A Detailed Method for Preparation of a Functional and Fl Exible Blood-Brain Barrier Model Using Porcine Brain Endothelial Cells","volume":"1521","author":"Patabendige","year":"2013","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jconrel.2018.07.016","article-title":"Monocultures of Primary Porcine Brain Capillary Endothelial Cells: Still a Functional in Vitro Model for the Blood-Brain-Barrier","volume":"285","author":"Galla","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3788","DOI":"10.1038\/s41598-020-60689-w","article-title":"A Dynamic Perfusion Based Blood-Brain Barrier Model for Cytotoxicity Testing and Drug Permeation","volume":"10","author":"Elbakary","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1046\/j.1471-4159.1998.71020705.x","article-title":"Mrp1 Multidrug Resistance-Associated Protein and P-Glycoprotein Expression in Rat Brain Microvessel Endothelial Cells","volume":"71","author":"Regina","year":"1998","journal-title":"J. Neurochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.brainres.2005.04.054","article-title":"Pericyte Abundance Affects Sucrose Permeability in Cultures of Rat Brain Microvascular Endothelial Cells","volume":"1049","author":"Parkinson","year":"2005","journal-title":"Brain Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"941","DOI":"10.3109\/00498254.2014.919430","article-title":"Temporal Expression of Transporters and Receptors in a Rat Primary Co-Culture Blood-Brain Barrier Model","volume":"44","author":"Liu","year":"2014","journal-title":"Xenobiotica"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/S1359-6446(00)01632-9","article-title":"Efflux Transport Systems for Drugs at the Blood-Brain Barrier and Blood-Cerebrospinal Fluid Barrier (Part 1)","volume":"6","author":"Kusuhara","year":"2001","journal-title":"Drug Discov. Today"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3389\/fncel.2019.00230","article-title":"A Novel Transwell Blood Brain Barrier Model Using Primary Human Cells","volume":"13","author":"Stone","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1006\/mpat.2000.0406","article-title":"Bacterial Invasion and Transcytosis in Transfected Human Brain Microvascular Endothelial Cells","volume":"30","author":"Stins","year":"2001","journal-title":"Microb. Pathog."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1038\/nprot.2010.76","article-title":"Establishment of Primary Cultures of Human Brain Microvascular Endothelial Cells to Provide an in Vitro Cellular Model of the Blood-Brain Barrier","volume":"5","author":"Bernas","year":"2010","journal-title":"Nat. Protoc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.brainres.2005.10.014","article-title":"Evaluation of the Immortalized Human Brain Capillary Endothelial Cell Line BB19 as a Human Cell Culture Model for the Blood-Brain Barrier","volume":"1064","author":"Drewe","year":"2005","journal-title":"Brain Res."},{"key":"ref_55","first-page":"166","article-title":"Comparison of a Rat Primary Cell-Based Blood-Brain Barrier Model with Epithelial and Brain Endothelial Cell Lines: Gene Expression and Drug Transport","volume":"11","author":"Veszelka","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s10571-004-1376-9","article-title":"Rat Brain Endothelial Cell Lines for the Study of Blood-Brain Barrier Permeability and Transport Functions","volume":"25","author":"Roux","year":"2005","journal-title":"Cell Mol. Neurobiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0006-8993(03)03443-7","article-title":"Evaluation of the Immortalised Mouse Brain Capillary Endothelial Cell Line, b.End3, as an in Vitro Blood-Brain Barrier Model for Drug Uptake and Transport Studies","volume":"990","author":"Omidi","year":"2003","journal-title":"Brain Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.brainres.2006.10.083","article-title":"Tight Junction Protein Expression and Barrier Properties of Immortalized Mouse Brain Microvessel Endothelial Cells","volume":"1130","author":"Brown","year":"2007","journal-title":"Brain Res."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Alamu, O., Rado, M., Ekpo, O., and Fisher, D. (2020). Differential Sensitivity of Two Endothelial Cell Lines to Hydrogen Peroxide Toxicity: Relevance for In Vitro Studies of the Blood-Brain Barrier. Cells, 9.","DOI":"10.3390\/cells9020403"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/jcbfm.2010.96","article-title":"Comparison of Immortalized BEnd5 and Primary Mouse Brain Microvascular Endothelial Cells as in Vitro Blood-\u039aBrain Barrier Models for the Study of T Cell Extravasation","volume":"31","author":"Steiner","year":"2011","journal-title":"J. Cereb. Blood Flow. Metab."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1113\/jphysiol.2005.084038","article-title":"Occludin as Direct Target for Glucocorticoid-Induced Improvement of Blood-Brain Barrier Properties in a Murine in Vitro System","volume":"565","author":"Silwedel","year":"2005","journal-title":"J. Physiol."},{"key":"ref_62","first-page":"e4022","article-title":"Generation of an Immortalized Murine Brain Microvascular Endothelial Cell Line as an in Vitro Blood Brain Barrier Model","volume":"66","author":"Burek","year":"2012","journal-title":"J. Vis. Exp."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1177\/1352458509358189","article-title":"Glucocorticoid Effects on Endothelial Barrier Function in the Murine Brain Endothelial Cell Line CEND Incubated with Sera from Patients with Multiple Sclerosis","volume":"16","author":"Blecharz","year":"2010","journal-title":"Mult. Scler."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Kaiser, M., Burek, M., Britz, S., Lankamp, F., Ketelhut, S., Kemper, B., F\u00f6rster, C., Gorzelanny, C., and Goycoolea, F.M. (2019). The Influence of Capsaicin on the Integrity of Microvascular Endothelial Cell Monolayers. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20010122"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.jneuroim.2006.06.019","article-title":"Differential Susceptibility of Cerebral and Cerebellar Murine Brain Microvascular Endothelial Cells to Loss of Barrier Properties in Response to Inflammatory Stimuli","volume":"179","author":"Silwedel","year":"2006","journal-title":"J. Neuroimmunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2162","DOI":"10.1021\/acs.molpharmaceut.9b00114","article-title":"Large-Scale Quantitative Comparison of Plasma Transmembrane Proteins between Two Human Blood-Brain Barrier Model Cell Lines, HCMEC\/D3 and HBMEC\/Ci\u03b2","volume":"16","author":"Masuda","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/2045-8118-10-16","article-title":"The HCMEC\/D3 Cell Line as a Model of the Human Blood Brain Barrier","volume":"10","author":"Weksler","year":"2013","journal-title":"Fluids Barriers CNS"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jneumeth.2012.10.001","article-title":"Immortalized Human Cerebral Microvascular Endothelial Cells Maintain the Properties of Primary Cells in an in Vitro Model of Immune Migration across the Blood Brain Barrier","volume":"212","author":"Daniels","year":"2013","journal-title":"J. Neurosci. Methods"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1021\/mp3004308","article-title":"Quantitative Targeted Absolute Proteomic Analysis of Transporters, Receptors and Junction Proteins for Validation of Human Cerebral Microvascular Endothelial Cell Line HCMEC\/D3 as a Human Blood-Brain Barrier Model","volume":"10","author":"Ohtsuki","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.ijpharm.2019.05.074","article-title":"Parametric Investigation of Static and Dynamic Cell Culture Conditions and Their Impact on HCMEC\/D3 Barrier Properties","volume":"566","author":"Hinkel","year":"2019","journal-title":"Int. J. Pharm."},{"key":"ref_71","first-page":"1513","article-title":"Limitations of the HCMEC\/D3 Cell Line as a Model for A b Clearance by the Human","volume":"1522","author":"Barrier","year":"2017","journal-title":"J. Neurosci. Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1002\/jcp.22232","article-title":"Establishment of a New Conditionally Immortalized Human Brain Microvascular Endothelial Cell Line Retaining an in Vivo Blood-Brain Barrier Function","volume":"225","author":"Sano","year":"2010","journal-title":"J. Cell Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/cen3.12001","article-title":"Stable Human Brain Microvascular Endothelial Cell Line Retaining Its Barrier-Specific Nature Independent of the Passage Number","volume":"4","author":"Sano","year":"2013","journal-title":"Clin. Exp. Neuroimmunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jns.2013.05.035","article-title":"NMO Sera Down-Regulate AQP4 in Human Astrocyte and Induce Cytotoxicity Independent of Complement","volume":"331","author":"Haruki","year":"2013","journal-title":"J. Neurol. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1080\/25785826.2018.1531190","article-title":"Blood\u2013Brain Barrier Dysfunction in Immuno-Mediated Neurological Diseases","volume":"41","author":"Shimizu","year":"2018","journal-title":"Immunol. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1111\/cen3.12045","article-title":"Establishment and Characterization of Spinal Cord Microvascular Endothelial Cell Lines","volume":"4","author":"Maeda","year":"2013","journal-title":"Clin. Exp. Neuroimmunol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"3286","DOI":"10.1002\/jcp.25772","article-title":"Establishment of a New Conditionally Immortalized Human Skeletal Muscle Microvascular Endothelial Cell Line","volume":"232","author":"Sano","year":"2017","journal-title":"J. Cell Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1111\/jnc.14068","article-title":"Astrocytes Contribute to A\u03b2-Induced Blood\u2013Brain Barrier Damage through Activation of Endothelial MMP9","volume":"142","author":"Spampinato","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1111\/cen3.12398","article-title":"Active Form of Vitamin D Directly Protects the Blood\u2013Brain Barrier in Multiple Sclerosis","volume":"8","author":"Takahashi","year":"2017","journal-title":"Clin. Exp. Neuroimmunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1128\/IAI.74.1.645-653.2006","article-title":"Platelets Potentiate Brain Endothelial Alterations Induced by Plasmodium Falciparum","volume":"74","author":"Wassmer","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.ijpharm.2018.09.040","article-title":"Assessment of HBEC-5i Endothelial Cell Line Cultivated in Astrocyte Conditioned Medium as a Human Blood-Brain Barrier Model for ABC Drug Transport Studies","volume":"551","author":"Puech","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3160360","DOI":"10.1155\/2017\/3160360","article-title":"HIV-1 Transactivator Protein Induces ZO-1 and Neprilysin Dysfunction in Brain Endothelial Cells via the Ras Signaling Pathway","volume":"2017","author":"Jiang","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.brainres.2012.09.042","article-title":"Establishment of a New Conditionally Immortalized Cell Line from Human Brain Microvascular Endothelial Cells: A Promising Tool for Human Blood-Brain Barrier Studies","volume":"1488","author":"Kamiichi","year":"2012","journal-title":"Brain Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/s12987-015-0003-0","article-title":"Hydrocortisone Enhances the Barrier Properties of HBMEC\/Ci\u03b2, a Brain Microvascular Endothelial Cell Line, through Mesenchymal-to-Endothelial Transition-like Effects","volume":"12","author":"Furihata","year":"2015","journal-title":"Fluids Barriers CNS"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4461","DOI":"10.1021\/acs.molpharmaceut.9b00519","article-title":"A Human Immortalized Cell-Based Blood-Brain Barrier Triculture Model: Development and Characterization as a Promising Tool for Drug-Brain Permeability Studies","volume":"16","author":"Ito","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Prashanth, A., Donaghy, H., Stoner, S.P., Hudson, A.L., Wheeler, H.R., Diakos, C.I., Howell, V.M., Grau, G.E., and McKelvey, K.J. (2021). Are in Vitro Human Blood\u2013Brain\u2013Tumor-barriers Suitable Replacements for in Vivo Models of Brain Permeability for Novel Therapeutics?. Cancers, 13.","DOI":"10.3390\/cancers13050955"},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Ferguson, R., and Subramanian, V. (2016). PA6 Stromal Cell Co-Culture Enhances SH- Differentiation to Mature Phenotypes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159051"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/978-1-62703-640-5_4","article-title":"Neuronal Cell Culture","volume":"1078","author":"Datta","year":"2013","journal-title":"Neuronal Cell Cult. Methods Protoc."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13024-017-0149-0","article-title":"The SH-SY5Y Cell Line in Parkinson\u2019 s Disease Research: A Systematic Review","volume":"12","author":"Xicoy","year":"2017","journal-title":"Mol. Neurodegener."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s00204-013-1120-7","article-title":"The Mixture of \u201cEcstasy\u201d and Its Metabolites Is Toxic to Human SH-SY5Y Differentiated Cells at in Vivo Relevant Concentrations","volume":"88","author":"Barbosa","year":"2014","journal-title":"Arch. Toxicol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1471-2121-12-43","article-title":"The MDCK Variety Pack: Choosing the Right Strain","volume":"12","author":"Dukes","year":"2011","journal-title":"BMC Cell Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.tibtech.2016.01.001","article-title":"Stem Cell-Based Human Blood-Brain Barrier Models for Drug Discovery and Delivery","volume":"34","author":"Aday","year":"2016","journal-title":"Trends Biotechnol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Minami, H., Tashiro, K., Okada, A., and Hirata, N. (2015). Generation of Brain Microvascular Endothelial-Like Cells from Human Induced Pluripotent Stem Cells by Co-Culture with C6 Glioma Cells. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0128890"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1177\/0271678X18788769","article-title":"In-Vitro Blood-Brain Barrier Modeling: A Review of Modern and Fast-Advancing Technologies","volume":"38","author":"Sivandzade","year":"2018","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12987-017-0059-0","article-title":"Accelerated Differentiation of Human Induced Pluripotent Stem Cells to Blood\u2013Brain Barrier Endothelial Cells","volume":"14","author":"Hollmann","year":"2017","journal-title":"Fluids Barriers CNS"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1177\/0271678X18783372","article-title":"Endothelial Cells Are Critical Regulators of Iron Transport in a Model of the Human Blood-Brain Barrier","volume":"39","author":"Chiou","year":"2019","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1038\/s41536-019-0083-6","article-title":"Mesenchymal Stem Cell Perspective: Cell Biology to Clinical Progress","volume":"4","author":"Pittenger","year":"2019","journal-title":"NPJ Regen. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41378-020-00208-z","article-title":"3D-Printed Electrochemical Sensor-Integrated Transwell Systems","volume":"6","author":"Chapin","year":"2020","journal-title":"Microsyst. Nanoeng."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Mondadori, C., Crippa, M., Moretti, M., Candrian, C., Lopa, S., and Arrigoni, C. (2020). Advanced Microfluidic Models of Cancer and Immune Cell Extravasation: A Systematic Review of the Literature. Front. Bioeng. Biotechnol., 8.","DOI":"10.3389\/fbioe.2020.00907"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.neuint.2008.12.002","article-title":"A New Blood-Brain Barrier Model Using Primary Rat Brain Endothelial Cells, Pericytes and Astrocytes","volume":"54","author":"Nakagawa","year":"2009","journal-title":"Neurochem. Int."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/nrn1824","article-title":"Astrocyte-Endothelial Interactions at the Blood-Brain Barrier","volume":"7","author":"Abbott","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.brainres.2009.05.072","article-title":"Closing the Gap between the In-Vivo and in-Vitro Blood-Brain Barrier Tightness","volume":"1284","author":"Malina","year":"2009","journal-title":"Brain Res."},{"key":"ref_103","first-page":"11.24.1","article-title":"Co-Culture of Neurons and Microglia","volume":"74","author":"Costa","year":"2017","journal-title":"Curr. Protoc. Toxicol."},{"key":"ref_104","unstructured":"Gomes, M.J., Mendes, B., Martins, S., and Sarmento, B. (2016). Concepts and Models for Drug Permeability Studies: Cell and Tissue Based In Vitro Culture Models, Woodhead Publishing."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.trac.2016.11.009","article-title":"Recent Advances in Microfluidic 3D Cellular Scaffolds for Drug Assays","volume":"87","author":"Wu","year":"2017","journal-title":"TrAC Trends Anal. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1002\/btm2.10013","article-title":"Microfluidics-based 3D Cell Culture Models: Utility in Novel Drug Discovery and Delivery Research","volume":"1","author":"Gupta","year":"2016","journal-title":"Bioeng. Transl. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1700489","DOI":"10.1002\/adhm.201700489","article-title":"In Vitro Microfluidic Models for Neurodegenerative Disorders","volume":"7","author":"Osaki","year":"2018","journal-title":"Adv. Healthc. Mater."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"8489","DOI":"10.1007\/s12035-019-01653-2","article-title":"Microfluidic Brain-on-a-Chip: Perspectives for Mimicking Neural System Disorders","volume":"56","author":"Abdoli","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/j.tibtech.2019.04.006","article-title":"Advances in Microfluidic Blood\u2013Brain Barrier (BBB) Models","volume":"37","author":"Oddo","year":"2019","journal-title":"Trends Biotechnol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.tiv.2004.06.011","article-title":"In Vitro Models for the Blood-Brain Barrier","volume":"19","author":"Garberg","year":"2005","journal-title":"Toxicol. Vitr."},{"key":"ref_111","first-page":"153","article-title":"Barrier Functionality of Porcine and Bovine Brain Capillary Endothelial Cells","volume":"1","author":"Nakhlband","year":"2011","journal-title":"BioImpacts"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.brainres.2012.08.031","article-title":"An Immortalised Astrocyte Cell Line Maintains the in Vivo Phenotype of a Primary Porcine in Vitro Blood-Brain Barrier Model","volume":"1479","author":"Cantrill","year":"2012","journal-title":"Brain Res."},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Thomsen, L.B., Burkhart, A., and Moos, T. (2015). A Triple Culture Model of the Blood-Brain Barrier Using Porcine Brain Endothelial Cells, Astrocytes and Pericytes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0134765"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mvr.2016.12.001","article-title":"Identification of Neuronal and Angiogenic Growth Factors in an in Vitro Blood-Brain Barrier Model System: Relevance in Barrier Integrity and Tight Junction Formation and Complexity","volume":"111","author":"Freese","year":"2017","journal-title":"Microvasc. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mex.2015.11.009","article-title":"MethodsX Optimization of an in Vitro Human Blood-Brain Barrier Model: Application to Blood Monocyte Transmigration Assays","volume":"3","author":"Paradis","year":"2016","journal-title":"MethodsX"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1016\/S0006-8993(01)03337-6","article-title":"A Co-Culture-Based Model of Human Blood-Brain Barrier: Application to Active Transport of Indinavir and in Vivo-in Vitro Correlation","volume":"927","author":"Megard","year":"2002","journal-title":"Brain Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jtice.2018.03.003","article-title":"Regulation of Human Brain Vascular Pericytes and Human Astrocytes in a Blood-Brain Barrier Model Using Human Brain Microvascular","volume":"86","author":"Kuo","year":"2018","journal-title":"J. Taiwan Inst. Chem. Eng."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jneumeth.2016.05.016","article-title":"Co-Culture Model Consisting of Human Brain Microvascular Endothelial and Peripheral Blood Mononuclear Cells","volume":"269","author":"Strazza","year":"2016","journal-title":"J. Neurosci. Methods"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ijpharm.2015.05.027","article-title":"In Fl Uence of Glioma Cells on a New Co-Culture in Vitro Blood-Brain Barrier Model for Characterization and Validation of Permeability","volume":"490","author":"Mendes","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12987-020-00212-5","article-title":"A Face-to-Face Comparison of Claudin-5 Transduced Human Brain Endothelial (HCMEC\/D3) Cells with Porcine Brain Endothelial Cells as Blood-Brain Barrier Models for Drug Transport Studies","volume":"17","author":"Gericke","year":"2020","journal-title":"Fluids Barriers CNS"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1007\/s11095-014-1519-8","article-title":"Permeability of PEGylated Immunoarsonoliposomes Through In Vitro Blood Brain Barrier-Medulloblastoma Co-Culture Models for Brain Tumor Therapy","volume":"32","author":"Favretto","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1016\/j.brainres.2016.04.024","article-title":"Immortalized Endothelial Cell Lines for in Vitro Blood-Brain Barrier Models: A Systematic Review","volume":"1642","author":"Adhwa","year":"2016","journal-title":"Brain Res."},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Yang, S., Mei, S., Jin, H., Zhu, B., Tian, Y., Huo, J., Cui, X., Guo, A., and Zhao, Z. (2017). Identification of Two Immortalized Cell Lines, ECV304 and BEnd3, for in Vitro Permeability Studies of Blood-Brain Barrier. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0187017"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/bit.26045","article-title":"Microfluidic Blood\u2013Brain Barrier Model Provides in Vivo-like Barrier Properties for Drug Permeability Screening","volume":"114","author":"Wang","year":"2017","journal-title":"Biotechnol. Bioeng."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1002\/stem.2908","article-title":"Barrier Properties and Transcriptome Expression in Human IPSC-Derived Models of the Blood\u2013Brain Barrier","volume":"36","author":"Delsing","year":"2018","journal-title":"Stem Cells"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1007\/s12264-019-00384-7","article-title":"Development of Human in Vitro Brain-Blood Barrier Model from Induced Pluripotent Stem Cell-Derived Endothelial Cells to Predict the in Vivo Permeability of Drugs","volume":"35","author":"Li","year":"2019","journal-title":"Neurosci. Bull."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1111\/jnc.13923","article-title":"An Isogenic Blood\u2013Brain Barrier Model Comprising Brain Endothelial Cells, Astrocytes, and Neurons Derived from Human Induced Pluripotent Stem Cells","volume":"140","author":"Canfield","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/s12987-019-0145-6","article-title":"An Isogenic Neurovascular Unit Model Comprised of Human Induced Pluripotent Stem Cell-Derived Brain Microvascular Endothelial Cells, Pericytes, Astrocytes, and Neurons","volume":"16","author":"Canfield","year":"2019","journal-title":"Fluids Barriers CNS"},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Noorani, B., Bhalerao, A., Raut, S., Nozohouri, E., Bickel, U., and Cucullo, L. (2021). A Quasi-Physiological Microfluidic Blood-Brain Barrier Model for Brain Permeability Studies. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13091474"},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Di Marco, A., Vignone, D., Gonzalez Paz, O., Fini, I., Battista, M.R., Cellucci, A., Bracacel, E., Auciello, G., Veneziano, M., and Khetarpal, V. (2020). Establishment of an in Vitro Human Blood-Brain Barrier Model Derived from Induced Pluripotent Stem Cells and Comparison to a Porcine. Cells, 9.","DOI":"10.3390\/cells9040994"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s12987-019-0136-7","article-title":"Role of IPSC-Derived Pericytes on Barrier Function of IPSC-Derived Brain Microvascular Endothelial Cells in 2D and 3D","volume":"16","author":"Jamieson","year":"2019","journal-title":"Fluids Barriers CNS"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1016\/j.stemcr.2019.05.008","article-title":"Stem Cell Reports","volume":"12","author":"Neal","year":"2019","journal-title":"Stem Cell Rep."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"623117","DOI":"10.3389\/fgene.2020.623117","article-title":"Review: In Vitro Cell Platform for Understanding Developmental Toxicity","volume":"11","author":"Xie","year":"2020","journal-title":"Front. Genet."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1080\/10408444.2020.1763253","article-title":"An Integrative Translational Framework for Chemical Induced Neurotoxicity\u2013a Systematic Review","volume":"50","author":"Deepika","year":"2020","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00204-016-1805-9","article-title":"In Vitro Acute and Developmental Neurotoxicity Screening: An Overview of Cellular Platforms and High-Throughput Technical Possibilities","volume":"91","author":"Schmidt","year":"2017","journal-title":"Arch. Toxicol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1124\/jpet.115.226373","article-title":"P-Glycoprotein Transport of Neurotoxic Pesticides","volume":"355","author":"Lacher","year":"2015","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.ntt.2008.12.003","article-title":"Relevance of in Vitro Neurotoxicity Testing for Regulatory Requirements: Challenges to Be Considered","volume":"32","author":"Hogberg","year":"2010","journal-title":"Neurotoxicol Teratol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/j.ijdevneu.2013.10.005","article-title":"In Vitro and in Vivo Study of Dolichyl Phosphate on the Efflux Activity of P-Glycoprotein at the Blood-Brain Barrier","volume":"31","author":"Ji","year":"2013","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41419-020-2626-6","article-title":"TNF-Alpha-Induced Microglia Activation Requires MiR-342: Impact on NF-KB Signaling and Neurotoxicity","volume":"11","author":"Bravo","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Cardoso, F.L., Kittel, \u00c1., Veszelka, S., Palmela, I., T\u00f3th, A., Brites, D., Deli, M.A., and Brito, M.A. (2012). Exposure to Lipopolysaccharide and\/or Unconjugated Bilirubin Impair the Integrity and Function of Brain Microvascular Endothelial Cells. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035919"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"2767","DOI":"10.1038\/s41598-020-59310-x","article-title":"OPEN A Co-Culture Nanofibre Scaffold Model of Neural Cell Degeneration in Relevance to Parkinson\u2019 s Disease","volume":"10","author":"Chemmarappally","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1177\/1091581817739428","article-title":"Human Co-Culture Model of Neurons and Astrocytes to Test Acute Cytotoxicity of Neurotoxic Compounds","volume":"36","author":"Caloni","year":"2017","journal-title":"Int. J. Toxicol."},{"key":"ref_143","doi-asserted-by":"crossref","unstructured":"Ariel, S., Gisele, M., Etcheverrito, A., Gustavo, D., and Ruth, D. (2020). Journal of Trace Elements in Medicine and Biology Neurotoxicity Mediated by Oxidative Stress Caused by Titanium Dioxide Nanoparticles in Human Neuroblastoma (SH-SY5Y) Cells. J. Trace Elem. Med. Biol., 57.","DOI":"10.1016\/j.jtemb.2019.126413"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.bbrc.2018.12.058","article-title":"The Effect of Glutamate-Induced Excitotoxicity on DNA Methylation in Astrocytes in a New in Vitro Neuron-Astrocyte-Endothelium Co-Culture System","volume":"508","author":"Zhao","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.vascn.2016.10.001","article-title":"Human Neuron-Astrocyte 3D Co-Culture-Based Assay for Evaluation of Neuroprotective Compounds","volume":"83","author":"Terrasso","year":"2017","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"671734","DOI":"10.3389\/fphar.2021.671734","article-title":"Neuroinflammatory In Vitro Cell Culture Models and the Potential Applications for Neurological Disorders","volume":"12","author":"Peng","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/nrd2368","article-title":"Modelling of the Blood-Brain Barrier in Drug Discovery and Development","volume":"6","author":"Cecchelli","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.drudis.2018.01.011","article-title":"Astrocytes as Targets for Drug Discovery","volume":"23","author":"Gorshkov","year":"2018","journal-title":"Drug Discov. Today"},{"key":"ref_149","doi-asserted-by":"crossref","unstructured":"Ju\u017awik, C.A., Drake, S.S., Zhang, Y., Paradis-Isler, N., Sylvester, A., Amar-Zifkin, A., Douglas, C., Morquette, B., Moore, C.S., and Fournier, A.E. (2019). MicroRNA Dysregulation in Neurodegenerative Diseases: A Systematic Review. Prog. Neurobiol., 182.","DOI":"10.1016\/j.pneurobio.2019.101664"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"3391","DOI":"10.3892\/mmr.2016.4948","article-title":"Role of Neuroinflammation in Neurodegenerative Diseases (Review)","volume":"13","author":"Chen","year":"2016","journal-title":"Mol. Med. Rep."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"11007","DOI":"10.1038\/s41598-020-67691-2","article-title":"Functional and Transcriptional Characterization of Complex Neuronal Co-Cultures","volume":"10","author":"Enright","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Mursaleen, L., Noble, B., Somavarapu, S., and Zariwala, M.G. (2021). Micellar Nanocarriers of Hydroxytyrosol Are Protective against Parkinson\u2019s Related Oxidative Stress in an in Vitro Hcmec\/D3-sh-sy5y Co-culture System. Antioxidants, 10.","DOI":"10.3390\/antiox10060887"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1146\/annurev.neuro.26.043002.094919","article-title":"Epidemiology of Neurodegeneration","volume":"26","author":"Mayeux","year":"2003","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Gunnarsson, L.G., and Bodin, L. (2019). Occupational Exposures and Neurodegenerative Diseases\u2014A Systematic Literature Review and Meta-Analyses. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16030337"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.neuro.2019.11.006","article-title":"Role of Monocarboxylate Transporter 4 in Alzheimer Disease","volume":"76","author":"Hong","year":"2020","journal-title":"Neurotoxicology"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/s41380-019-0468-3","article-title":"Modeling Alzheimer\u2019s Disease with IPSC-Derived Brain Cells","volume":"25","author":"Penney","year":"2020","journal-title":"Mol. Psychiatry"},{"key":"ref_157","doi-asserted-by":"crossref","unstructured":"Monteiro, A.R., Barbosa, D.J., Remi\u00e3o, F., and Silva, R. (2023). Alzheimer\u2019s Disease: Insights and New Prospects in Disease Pathophysiology, Biomarkers and Disease-Modifying Drugs. Biochem. Pharmacol., 211.","DOI":"10.1016\/j.bcp.2023.115522"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.neuint.2017.04.014","article-title":"Poly(ADP-Ribose) Polymerase-1 Regulates Microglia Mediated Decrease of Endothelial Tight Junction Integrity","volume":"108","author":"Mehrabadi","year":"2017","journal-title":"Neurochem. Int."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"8916","DOI":"10.1007\/s12035-018-0985-0","article-title":"Evidence for Compromised Insulin Signaling and Neuronal Vulnerability in Experimental Model of Sporadic Alzheimer\u2019s Disease","volume":"55","author":"Gupta","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"337","DOI":"10.3389\/fncel.2019.00337","article-title":"Astrocytes Modify Migration of Pbmcs Induced by \u03b2-Amyloid in a Blood-Brain Barrier in Vitro Model","volume":"13","author":"Spampinato","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1007\/s11095-019-2691-7","article-title":"ApoE-2 Brain-Targeted Gene Therapy Through Transferrin and Penetratin Tagged Liposomal Nanoparticles","volume":"36","author":"Kanekiyo","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Topal, G.R., M\u00e9sz\u00e1ros, M., Porkol\u00e1b, G., Szecsk\u00f3, A., Polg\u00e1r, T.F., Sikl\u00f3s, L., Deli, M.A., Veszelka, S., and Bozkir, A. (2021). ApoE-Targeting Increases the Transfer of Solid Lipid Nanoparticles with Donepezil Cargo across a Culture Model of the Blood\u2013Brain Barrier. Pharmaceutics, 13.","DOI":"10.3390\/pharmaceutics13010038"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.neuropharm.2018.09.008","article-title":"Streptocyclinones A and B Ameliorate Alzheimer\u2019s Disease Pathological Processes in Vitro","volume":"141","author":"Alonso","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"6826","DOI":"10.7150\/thno.72685","article-title":"A Sporadic Alzheimer\u2019s Blood-Brain Barrier Model for Developing Ultrasound-Mediated Delivery of Aducanumab and Anti-Tau Antibodies","volume":"12","author":"Wasielewska","year":"2022","journal-title":"Theranostics"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.nbd.2018.07.030","article-title":"A Differentiating Neural Stem Cell-Derived Astrocytic Population Mitigates the Inflammatory Effects of TNF-\u03b1 and IL-6 in an IPSC-Based Blood-Brain Barrier Model","volume":"119","author":"Mantle","year":"2018","journal-title":"Neurobiol. Dis."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1016\/j.stemcr.2017.05.017","article-title":"A Highly Efficient Human Pluripotent Stem Cell Microglia Model Displays a Neuronal-Co-Culture-Specific Expression Profile and Inflammatory Response","volume":"8","author":"Haenseler","year":"2017","journal-title":"Stem Cell Rep."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.bbadis.2016.11.025","article-title":"Necroptosis in Amyotrophic Lateral Sclerosis and Other Neurological Disorders","volume":"1863","author":"Morrice","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1093\/brain\/awz419","article-title":"Distinct Responses of Neurons and Astrocytes to TDP-43 Proteinopathy in Amyotrophic Lateral Sclerosis","volume":"143","author":"Smethurst","year":"2020","journal-title":"Brain"},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3389\/fnsyn.2014.00010","article-title":"The Role of D-Serine and Glycine as Co-Agonists of NMDA Receptors in Motor Neuron Degeneration and Amyotrophic Lateral Sclerosis (ALS)","volume":"6","author":"Paul","year":"2014","journal-title":"Front. Synaptic Neurosci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"6910","DOI":"10.1007\/s12035-015-9567-6","article-title":"Disruption of TCA Cycle and Glutamate Metabolism Identified by Metabolomics in an In Vitro Model of Amyotrophic Lateral Sclerosis","volume":"53","author":"Corcia","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/jnc.14135","article-title":"Brain Endothelial Cells Induce Astrocytic Expression of the Glutamate Transporter GLT-1 by a Notch-Dependent Mechanism","volume":"143","author":"Lee","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.expneurol.2019.04.002","article-title":"Excess Glutamate Secreted from Astrocytes Drives Upregulation of P-Glycoprotein in Endothelial Cells in Amyotrophic Lateral Sclerosis","volume":"316","author":"Mohamed","year":"2019","journal-title":"Exp. Neurol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.1111\/bph.13193","article-title":"Prevention of the Degeneration of Human Dopaminergic Neurons in an Astrocyte Co-Culture System Allowing Endogenous Drug Metabolism","volume":"172","author":"Efremova","year":"2015","journal-title":"Br. J. Pharmacol."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/glia.21112","article-title":"Astrocyte-Derived Metallothionein Protects Dopaminergic Neurons from Dopamine Quinone Toxicity","volume":"59","author":"Miyazaki","year":"2011","journal-title":"Glia"},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Sergi, D., Alex, G., Beaulieu, J., Renaud, J., Tardif-pellerin, E., and Martinoli, M. (2021). \u03b5-Viniferin in a Neuron-Glia Co-Culture Cellular Model of Parkinson\u2019 s Disease. Foods, 10.","DOI":"10.3390\/foods10030586"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Johnson, S.L., Park, H.Y., Dasilva, N.A., Ma, H., and Seeram, N.P. (2018). Levodopa-Reduced Mucuna Pruriens Seed Extract Shows Neuroprotective Effects against Parkinson\u2019 s Disease in Murine Microglia and Human. Nutrients, 10.","DOI":"10.3390\/nu10091139"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.expneurol.2016.09.003","article-title":"\u03b1-Synuclein Pre-Formed Fibrils Impair Tight Junction Protein Expression without Affecting Cerebral Endothelial Cell Function","volume":"285","author":"Kuan","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.mvr.2019.03.005","article-title":"Monomeric \u03b1-Synuclein Induces Blood\u2013Brain Barrier Dysfunction through Activated Brain Pericytes Releasing Inflammatory Mediators in Vitro","volume":"124","author":"Dohgu","year":"2019","journal-title":"Microvasc. Res."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.neulet.2012.07.004","article-title":"Lipopolysaccharide-Activated Microglia Lower P-Glycoprotein Function in Brain Microvascular Endothelial Cells","volume":"524","author":"Matsumoto","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_180","doi-asserted-by":"crossref","unstructured":"Liu, Q., Hou, J., Chen, X., Liu, G., Zhang, D., Sun, H., and Zhang, J. (2014). P-Glycoprotein Mediated Efflux Limits the Transport of the Novel Anti-Parkinson\u2019s Disease Candidate Drug FLZ across the Physiological and PD Pathological in Vitro BBB Models. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0102442"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"103501","DOI":"10.1016\/j.mcn.2020.103501","article-title":"Decoding Parkinson\u2019s Disease\u2014IPSC-Derived Models in the OMICs Era","volume":"106","author":"Krach","year":"2020","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"124","DOI":"10.3389\/fncel.2019.00571","article-title":"Modeling Cell-Cell Interactions in Parkinson\u2019s Disease Using Human Stem Cell-Based Models","volume":"13","author":"Simmnacher","year":"2020","journal-title":"Front. Cell Neurosci."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s12974-021-02158-3","article-title":"Crosstalk between Astrocytes and Microglia Results in Increased Degradation of \u03b1-Synuclein and Amyloid-\u03b2 Aggregates","volume":"18","author":"Rostami","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s12987-019-0139-4","article-title":"The Role of Mutations Associated with Familial Neurodegenerative Disorders on Blood\u2013Brain Barrier Function in an IPSC Model","volume":"16","author":"Katt","year":"2019","journal-title":"Fluids Barriers CNS"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"6581","DOI":"10.1038\/s41467-022-34412-4","article-title":"Reactive Astrocytes Transduce Inflammation in a Blood-Brain Barrier Model through a TNF-STAT3 Signaling Axis and Secretion of Alpha 1-Antichymotrypsin","volume":"13","author":"Kim","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"3753","DOI":"10.1038\/s41467-020-17514-9","article-title":"Knockout of Reactive Astrocyte Activating Factors Slows Disease Progression in an ALS Mouse Model","volume":"11","author":"Guttenplan","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/s41591-018-0051-5","article-title":"Block of A1 Astrocyte Conversion by Microglia Is Neuroprotective in Models of Parkinson\u2019s Disease","volume":"24","author":"Yun","year":"2018","journal-title":"Nat. Med."}],"container-title":["Biomedicines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9059\/12\/3\/626\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:12:20Z","timestamp":1760105540000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9059\/12\/3\/626"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,12]]},"references-count":187,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["biomedicines12030626"],"URL":"https:\/\/doi.org\/10.3390\/biomedicines12030626","relation":{},"ISSN":["2227-9059"],"issn-type":[{"value":"2227-9059","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,12]]}}}