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

• Material Type: 博士論文
• Title: MAP Kinase Pathways in Brain Endothelial Cells and Crosstalk with Pericytes and Astrocytes Mediate Contrast-Induced Blood–Brain Barrier Disruption
• Author/Editor: 松永, 裕希
• Author Heading: 松永, 裕希
• Publication, Distribution, etc.: MDPI
• Publication Date: 2022-03-18
• Publication Date (W3CDTF): 2022-03-18
• Alternative Title: 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
• Periodical title: Pharmaceutics
• No. or year of volume/issue: 13 8
• Volume: 13
• Issue: 8
• Pages: 1272-
• ISSN (Periodical Title): ISSN : 1999-4923
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2022-03-18
• Dissertation Number: 甲医歯薬第1420号
• Degree Type: 博士(医学)
• Text Language Code: eng
• Subject Heading: blood–brain barrier; contrast media; iopamidol; MAP kinase; pericytes; astrocytes; neurointervention; contrast-induced encephalopathy
• Target Audience: 一般
• Note (General): 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)
• Source: 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
• Access Restrictions: インターネット公開
• Rights (production): © 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/).
• Related Material: http://hdl.handle.net/10069/00041423
• Related Material (DOI): 10.3390/pharmaceutics13081272
• Data Provider (Database): 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
• Original Data Provider (Database): 長崎大学 : 長崎大学学術研究成果リポジトリ