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Abstracts from the 13Th International Conference on Cerebral Vascular Biology (CVB 2019)

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Abstracts from the 13Th International Conference on Cerebral Vascular Biology (CVB 2019) Fluids Barriers CNS 2019, 16(Suppl 1):16 https://doi.org/10.1186/s12987-019-0135-8 Fluids and Barriers of the CNS MEETING ABSTRACTS Open Access Abstracts from the 13th International Conference on Cerebral Vascular Biology (CVB 2019) Miami, FL, USA. 25-28 June 2019 Published: 20 June 2019 I1 vasculature that can be applied to therapy. Other emerging topics dis- 13th International Conference on Cerebral Vascular Biology cussed during the conference will involve impact of life style on modu- Michal Toborek lation of brain barriers, cerebrovascular pathology of the aging brain, University of Miami School of Medicine, Miami, FL targeting cerebral vasculature for regenerative medicine, and the role Correspondence: Michal Toborek ‑ [email protected] of the gut-brain axis. Several activities will be dedicated to trainees, Fluids and Barriers of the CNS 2019, 16(Suppl 1):I1 early stage investigators, and the inclusion of researchers from under- represented groups. The conference strongly promotes ethnic and The 13th International Conference on Cerebral Vascular Biology (CVB gender diversity among the speakers and participants. 2019; http://www.CVB20 19.com) is being organized at the Marriott The major sponsors of CVB 2019 include the NIH (NINDS, NIA, and Miami Biscayne Bay hotel from June 25–28, 2019 in Miami, FL. The NHLBI) that supports, via the R13 grant mechanism, participation of CVB conferences are bi-annual meetings that provide a forum for sci- trainees and early stage investigators, with the emphasis on individu- entists from around the world to discuss their cutting edge research als from under-represented groups. In addition, the NIMH sponsors the on cerebral vascular biology with a focus on CNS barriers, primarily session on strategies of drug delivery into the brain in order to eradi- the blood–brain barrier (BBB). CVB 2019 in Miami will be a continua- cate HIV reservoirs. The Platinum Sponsors of CVB 2019 are the Uni- tion of a very successful conference series that was initiated in 1992. To versity of Miami Clinical and Translational Science Institute (CTSI) and emphasize the importance and international focus of the CVB series, the Jerzy Kukuczka Academy of Physical Education in Poland. The Gold the conferences rotate between North America, Europe, and Asia/Aus- Sponsors are the Department of Biochemistry and Molecular Biology, tralia (1992, Duluth, MN; 1995, Paris, France; 1998, Salishan, OR; 2001, the Miami Project to Cure Paralysis, the McKnight Brain Institute (all Cambridge, UK; 2003, Amarillo, TX; 2005, Muenster, Germany; 2007, at the University of Miami), Florida International University (FIU), and Ottawa, Canada; 2009, Sendai, Japan; 2011, Leiden, The Netherlands; Biogen. Several commercial companies, the Nagai Foundation Tokyo, 2013, Montreal, Canada; 2015, Paris, France; 2017, Melbourne, Aus- the Johns Hopkins Malaria Research Institute, the Nebraska Center tralia). Since the formation of the International Brain Barriers Society for Substance Abuse Research at the University of Nebraska Medical (IBBS) in 2006, CVB conferences are organized under the general aus- Center, and the Department of Surgery at the University of Miami are pices of the IBBS. the Silver Sponsors. Finally, the IBBS, Fluids and Barriers of the CNS, CVB 2019 is being attended by scientists from a broad range of back- and private donors are the Bronze Sponsors and provide poster and grounds and disciplines who share a common interest in cerebral research awards to trainees. vascular biology. By bringing together scientists from diverse back- grounds in basic, translational, and clinical research, the meeting promotes the emergence of common themes across cerebrovascular A1 topics. This will structure strategies for successful therapeutic interven- A novel human immortalized cell‑based blood–brain barrier triple tions in the brain diseases that have strong cerebrovascular compo- co‑culture model for predicting brain permeability of CNS drug nents and/or are underlined by the dysfunction of the BBB. The overall candidates Keita Kitamura1, Kenta Umehara1, Ryo Ito2, Shota Suzuki1, Yoshiyuki goal of CVB 2019 is to serve as a catalyst for exchange of information 2 3 1 1 Yamaura , Takafumi Komori , Naohiko Anzai , Hidetaka Akita , Tomomi on the latest scientifc discoveries related to the bioengineering of the 1 BBB, efcient drug delivery into the brain, and involvement of the BBB Furihata 1Chiba University, Chiba, Japan; 2Ono Pharmaceutical Co., Ltd, Osaka, in the physiology and pathology of the brain, including neuroinfec- 3 tions, neurodegenerative diseases, and addiction research. Consistent Japan; Eisai Co., Ltd., Tokoyo, Japan with this goal, the conference is focused on current and future research Correspondence: Keita Kitamura ‑ ahha4394@chiba‑u.jp surrounding cerebral vascular biology, such as biology and structure Fluids and Barriers of the CNS 2019, 16(Suppl 1):A1 of the neurovascular unit and cell junction proteins, constructing and Objective: In vitro human blood–brain barrier (BBB) models are modeling the BBB, delivery of various types of drugs across the BBB, expected to provide powerful tools for predicting in vivo human brain the role of brain barriers in the pathology of neurological diseases, penetration of central nervous system (CNS) drug candidates, while it and therapeutic strategies to reverse these diseases by targeting the has not yet been fully established a practical model that possesses an brain barriers. Emphasis are being placed on integrative science, trans- optimal BBB phenotype and is readily scalable. To this end, we have lational aspects, and clinical research on disorders involving cerebral developed and characterized a human BBB triple co-culture model © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creat iveco mmons .org/licen ses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/ publi cdoma in/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Fluids Barriers CNS 2019, 16(Suppl 1):16 Page 2 of 57 comprising brain microvascular endothelial cells (BMEC), astrocyte Conclusion: This novel in vitro device for BBB culture models provides and pericyte by taking advantage of immortalized cell line utility that users with a standardized, reliable and reusable platform to perform allows various experimental approaches. pathology and pharmacology experiments. With advancement of the Methods: A human BBB model was constructed using immortalized electrode layout, TEER automation and surface potential measurement human BMEC (HBMEC/ci18), astrocyte (HASTR/ci35), pericyte (HPBC/ our device is a cutting edge invention in the barrier-chip feld. ci37). The gene expressions were determined by qPCR and immuno- Grant Support: This work was supported by the European Training Net- cytochemistry. The BBB functions were examined by determining work H2020-MSCA-ITN-2015, grant number 675619, and NNE-129. transendothelial electric resistance (TEER), lucifer yellow (LY) permea- bility and P-glycoprotein (P-gp) bi-directional transport. In the perme- Reference ability assay, compounds were quantifed by LC–MS/MS system. 1. Walter FR, Valkai S, Kincses A, Petneházi A, Czeller T, Veszelka S, Ormos Results: HBMEC/ci18 co-cultured with HASTR/ci35 and HBPC/ci37 P, Deli MA, Dér A. A versatile lab‑on‑a‑chip tool for modeling biological showed elevated TEER (2.0-fold), reduced LY permeability (0.7-fold) barriers. Sens Actuators B Chem. 2016; 222:1209–19. and increased P-gp function (1.4-fold) compared with mono-culture. In support of these fndings, expression levels of multiple BBB-specifc A3 genes, including barrier formation, transporters and receptors, were Absolute computed tomography indicators of blood brain barrier increased as well as their typical cellular localization in co-culture permeability and cerebral microperfusion improve long term model. Notably, we performed BBB permeability assays using a set of 9 after carotid stenting in symptomatic patients compounds with known CNS permeability characteristics. Expectedly, Paweł J. Winklewski1, Mariusz Kaszubowski2, Grzegorz Halena1, Agnieszka 1 1 1 1 CNS-positive compounds (memantine, diphenhydramine, proprano- Sabisz , Kamil Chwojnicki , Maciej Piskunowicz , Marta A. Małkiewicz , lol and pyrilamine) displayed high permeability coefcient values (Pe) 1 1 6 Edyta Szurowska , Arkadiusz Szarmach (522 100 to 1398 324 10− cm/s). In contrast, CNS-negative com- 1Medical University of Gdansk, Gdansk, Poland; 2Gdansk Tecchnical pounds± (quinidine,± desloratadine,× rhodamine 123, LY, sodium fuores- 6 University, Gdansk, Poland cein) showed low Pe (21 11 to 161 31 10− cm/s). ± ± × Correspondence: Paweł J. Winklewski ‑ [email protected] Conclusion: We successfully developed a functional and scalable Fluids and Barriers of the CNS 2019, 16(Suppl 1):A3 human BBB model. We hope that such research eforts are likely to open up new possibility of quantitative prediction of human CNS Objectives: Strong interdependence between severity of microcir- action based on in vitro experiment. culation impairment and time-based perfusion parameters has been recently reported. In particular, mean
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