Cilostazol attenuates ischemia–reperfusion-induced blood–brain barrier dysfunction enhanced by advanced glycation endproducts via transforming growth factor-β1 signaling

We investigated the effects of cilostazol, a selective inhibitor of phosphodiesterase 3, on blood-brain barrier (BBB) integrity against ischemia-reperfusion injury enhanced by advanced glycation endproducts (AGEs). We used in vitro BBB models with primarily cultured BBB-related cells from rats (brain capillary endothelial cells, astrocytes and pericytes), and subjected cells to either normoxia or 3-h oxygen glucose deprivation (OGD)/24-h reoxygenation with or without AGEs. Treatment of AGEs did not affect the transendothelial electrical resistance (TEER) in the BBB model under normoxia, but there was a significant decrease in TEER under 3-h OGD/24-h reoxygenation conditions with AGEs. Cilostazol inhibited decreases in TEER induced by 3-h OGD/24-h reoxygenation with AGEs. Immunocytochemical and Western blot analyses showed that AGEs reduced the expression of claudin-5, the main functional protein of tight junctions (TJs). In contrast, cilostazol increased the expression of claudin-5 under 3-h OGD/24-h reoxygenation with AGEs. Furthermore, while AGEs increased the production of extracellular transforming growth factor (TGF)-β1, cilostazol inhibited the production of extracellular TGF-β1 and restored the integrity of TJs. Thus, we found that AGEs enhanced ischemia-reperfusion injury, which mainly included decreases in the expression of proteins comprising TJs through the production of TGF-β1. Cilostazol appeared to limit ischemia-reperfusion injury with AGEs by improving the TJ proteins and inhibiting TGF-β1 signaling.;開始ページ : 1;終了ページ : 9;元資料の権利情報 : © 2014 Elsevier Inc.;元資料の権利情報 : NOTICE: this is the author's version of a work that was accepted for publication in Molecular and Cellular Neuroscience. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Molecular and Cellular Neuroscience, 60, (2014)

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書名 Cilostazol attenuates ischemia–reperfusion-induced blood–brain barrier dysfunction enhanced by advanced glycation endproducts via transforming growth factor-β1 signaling
著作者等 竹下 朝規
書名別名 トランスフォーミング増殖因子-β1を介した虚血再灌流条件下での終末糖化産物による血液脳関門障害に対するシロスタゾールの保護効果.
出版元 Academic Press
刊行年月 1990-
ページ数 v.
大きさ 28 cm
ISSN 10447431
NCID AA10808088
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言語 英語
出版国 アメリカ合衆国
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