MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier Disruption

• 資料種別: 博士論文
• タイトル: MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier Disruption
• 著者・編者: 松永, 裕希
• 著者標目: 松永, 裕希
• 出版事項: MDPI
• 出版年月日等: 2022-03-18
• 出版年（W3CDTF）: 2022-03-18
• 並列タイトル等: 脳毛細血管内皮細胞におけるMAP kinase経路とペリサイト、アストロサイトのクロストークが造影剤誘発性血液脳関門障害に関与する
• タイトル（掲載誌）: Pharmaceutics
• 巻号年月日等（掲載誌）: 13 8
• 掲載巻: 13
• 掲載号: 8
• 掲載ページ: 1272-
• ISSN（掲載誌）: ISSN : 1999-4923
• 授与機関名: Nagasaki University (長崎大学)
• 授与年月日: 2022-03-18
• 報告番号: 甲医歯薬第1420号
• 学位: 博士(医学)
• 本文の言語コード: eng
• 件名標目: blood–brain barrier; contrast media; iopamidol; MAP kinase; pericytes; astrocytes; neurointervention; contrast-induced encephalopathy
• 対象利用者: 一般
• 一般注記: Neurointervention with contrast media (CM) has rapidly increased, but the impact of CM extravasation and the related side effects remain controversial. This study investigated the effect of CM on blood–brain barrier (BBB) integrity. We established in vitro BBB models using primary cultures of rat BBB-related cells. To assess the effects of CM on BBB functions, we evaluated transendothelial electrical resistance, permeability, and tight junction (TJ) protein expression using immunohistochemistry (IHC) and Western blotting. To investigate the mechanism of iopamidol-induced barrier dysfunction, the role of mitogen-activated protein (MAP) kinases in brain endothelial cells was examined. We assessed the effect of conditioned medium derived from astrocytes and pericytes under iopamidol treatment. Short-term iopamidol exposure on the luminal side induced transient, while on the abluminal side caused persistent BBB dysfunction. IHC and immunoblotting revealed CM decreased the expression of TJ proteins. Iopamidol-induced barrier dysfunction was improved via the regulation of MAP kinase pathways. Conditioned medium from CM-exposed pericytes or astrocytes lacks the ability to enhance barrier function. CM may cause BBB dysfunction. MAP kinase pathways in brain endothelial cells and the interactions of astrocytes and pericytes mediate iopamidol-induced barrier dysfunction. CM extravasation may have negative effects on clinical outcomes in patients.; 長崎大学学位論文 学位記番号:博(医歯薬)甲第1420号 学位授与年月日:令和4年3月18日; Author: Yuki Matsunaga, Shinsuke Nakagawa, Yoichi Morofuji, Shinya Dohgu, Daisuke Watanabe, Nobutaka Horie, Tsuyoshi Izumo, Masami Niwa, Fruzsina R. Walter, Ana Raquel Santa-Maria, Maria A. Deli and Takayuki Matsuo; Citation: Pharmaceutics, 13(8), art.no. 1272; 2021; identifier:Nagasaki University (長崎大学), 博士(医学) (2022-03-18)
• 一次資料へのリンクURL: https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27396&item_no=1&attribute_id=70&file_no=1 （fulltext）; https://nagasaki-u.repo.nii.ac.jp/?action=repository_action_common_download&item_id=27396&item_no=1&attribute_id=70&file_no=1
• オンライン閲覧公開範囲: インターネット公開
• 著作権情報: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/4.0/).
• 関連情報: http://hdl.handle.net/10069/00041423
• 関連情報（DOI）: 10.3390/pharmaceutics13081272
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 長崎大学 : 長崎大学学術研究成果リポジトリ