caa a22 4500 463254260 CHVBK 20180405153350.0 cr unu---uuuuu 170326e20071101xx s 000 0 eng 10.1007/s10571-007-9209-2 doi (NATIONALLICENCE)springer-10.1007/s10571-007-9209-2 Adverse Effect of Cyclosporin A on Barrier Functions of Cerebral Microvascular Endothelial Cells After Hypoxia-reoxygenation Damage InVitro [Elektronische Daten] [Shinya Dohgu, Tsuyoshi Nishioku, Noriko Sumi, Fuyuko Takata, Shinsuke Nakagawa, Mikihiko Naito, Takashi Tsuruo, Atsushi Yamauchi, Hideki Shuto, Yasufumi Kataoka] Hypoxia and post-hypoxic reoxygenation induces disruption of the blood-brain barrier (BBB). Alterations of the BBB function after hypoxia/reoxygenation (H/R) injury remain unclear. Cyclosporin A (CsA), a potent immunosuppressant, induces neurotoxic effects by entering the brain, although the transport of CsA across the BBB is restricted by P-glycoprotein (P-gp), a multidrug efflux pump, and tight junctions of the brain capillary endothelial cells. The aim of this study was to evaluate whether the BBB after H/R damage is vulnerable to CsA-induced BBB dysfunction. We attempted to establish a pathophysiological BBB model with immortalized mouse brain capillary endothelial (MBEC4) cells. The effects of CsA on permeability and P-gp activity of the MBEC4 cells were then examined. Exposure to hypoxia for 4h and reoxygenation for 1h (H/R (4h/1h)) produced a significant decrease in P-gp function of MBEC4 cells, without changing cell viability and permeability for sodium fluorescein and Evan's blue-albumin at 7days after H/R (4h/1h). CsA-induced hyperpermeability and P-gp dysfunction in MBEC4 monolayers at 7days after H/R (4h/1h) were exacerbated. The possibility that CsA penetrates the BBB with incomplete functions in the vicinity of cerebral infarcts to induce neurotoxicity has to be considered. Springer Science+Business Media, LLC, 2007 Blood-brain barrier nationallicence Cyclosporin A nationallicence Hypoxia/reoxygenation nationallicence Oxygen-glucose deprivation nationallicence Mouse brain capillary endothelial cells nationallicence MBEC4 cells nationallicence P-glycoprotein nationallicence Permeability nationallicence Dohgu Shinya Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut Nishioku Tsuyoshi Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut Sumi Noriko Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut Takata Fuyuko Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut Nakagawa Shinsuke Department of Pharmacology 1, Graduate School of Medicine, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan aut Naito Mikihiko Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, 113-0032, Tokyo, Japan aut Tsuruo Takashi Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, 113-0032, Tokyo, Japan aut Yamauchi Atsushi Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut Shuto Hideki Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut Kataoka Yasufumi Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/7(2007-11-01), 889-899 0272-4340 27:7<889 2007 27 10571 https://doi.org/10.1007/s10571-007-9209-2 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10571-007-9209-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Dohgu Shinya Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut NATIONALLICENCE 700 1- Nishioku Tsuyoshi Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut NATIONALLICENCE 700 1- Sumi Noriko Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut NATIONALLICENCE 700 1- Takata Fuyuko Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut NATIONALLICENCE 700 1- Nakagawa Shinsuke Department of Pharmacology 1, Graduate School of Medicine, Nagasaki University, 1-12-4 Sakamoto, 852-8523, Nagasaki, Japan aut NATIONALLICENCE 700 1- Naito Mikihiko Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, 113-0032, Tokyo, Japan aut NATIONALLICENCE 700 1- Tsuruo Takashi Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, 113-0032, Tokyo, Japan aut NATIONALLICENCE 700 1- Yamauchi Atsushi Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut NATIONALLICENCE 700 1- Shuto Hideki Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut NATIONALLICENCE 700 1- Kataoka Yasufumi Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, 814-0180, Fukuoka, Japan aut NATIONALLICENCE 773 0- Cellular and Molecular Neurobiology Springer US; http://www.springer-ny.com 27/7(2007-11-01), 889-899 0272-4340 27:7<889 2007 27 10571 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer