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Candesartan Improves Ischemia-Induced Impairment of the Blood–Brain Barrier In Vitro

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Title: Candesartan Improves Ischemia-Induced Impairment of the Blood–Brain Barrier In Vitro
Other Titles: カンデサルタンは生体外で虚血により引き起こされた血液脳関門の障害を改善する
Authors: 宗, 剛平
Authors (alternative): So, Gohei
Issue Date: 18-Mar-2015
Publisher: Springer New York LLC
Citation: Nagasaki University (長崎大学), 博士(医学) (2015-03-18)
Abstract: Candesartan has been reported to have a protective effect on cerebral ischemia in vivo and in human ischemic stroke. We studied the direct effects of candesartan on blood–brain barrier (BBB) function with our in vitro monolayer model generated using rat brain capillary endothelial cells (RBECs). The in vitro BBB model was subjected to normoxia or 6-h oxygen glucose deprivation (OGD)/24-h reoxygenation, with or without candesartan. 6-h OGD/24-h reoxygenation decreased transendothelial electrical resistance and increased the endothelial permeability for sodium fluorescein in RBEC monolayers. Candesartan (10 nM) improved RBEC barrier dysfunction induced by 6-h OGD/24-h reoxygenation. Immunostaining and immunoblotting analysis indicated that the effect of candesartan on barrier function under 6-h OGD/24-h reoxygenation was not related to the expression levels of tight junction proteins. However, candesartan affected RBEC morphological changes induced by 6-h OGD/24-h reoxygenation. We analyzed oxidative stress and cell viability using chemical reagents. Candesartan improved cell viability following 6-h OGD/24-h reoxygenation, whereas candesartan had no effect on oxidative stress. These results show that candesartan directly improves cell function and viability of brain capillary endothelial cells under OGD/reoxygenation, suggesting that the protective effects of candesartan on ischemic stroke are related to protection of the BBB.
Description: 長崎大学学位論文 学位記番号:博(医歯薬)甲第753号 学位授与年月日:平成27年3月18日 / Author: Gohei So, Shinsuke Nakagawa, Yoichi Morofuji, Takeshi Hiu, Kentaro Hayashi, Kunihiko Tanaka, Kazuhiko Suyama, Maria A. Deli, Izumi Nagata, Takayuki Matsuo, Masami Niwa / Citation: Cellular and Molecular Neurobiology, 35(4), pp.563-572; 2015
Keywords: Blood–brain barrier / Candesartan / Oxygen glucose deprivation / Reoxygenation / Tight junctions / Transendothelial electrical resistance
URI: http://hdl.handle.net/10069/35458
ISSN: 02724340
DOI: 10.1007/s10571-014-0152-8
Relational Links: http://hdl.handle.net/10069/35629
Rights: (c)2014 Springer Science+Business Media New York / The final publication is available at link.springer.com
Type: Thesis or Dissertation
Text Version: ETD
Appears in Collections:dissertation

Citable URI : http://hdl.handle.net/10069/35458

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