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The tight junction protein occludin modulates blood–brain barrier integrity and neurological function after ischemic stroke in mice
Blood–brain barrier (BBB) disruption contributes to brain injury and neurological impairment. Tight junctions (TJs) and cell–cell adhesion complexes develop between endothelial cells in the brain to establish and maintain the BBB. Occludin, the first transmembrane protein identified in TJs, has rece...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9938878/ https://www.ncbi.nlm.nih.gov/pubmed/36806348 http://dx.doi.org/10.1038/s41598-023-29894-1 |
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author | Sugiyama, Shintaro Sasaki, Tsutomu Tanaka, Hiroo Yan, Haomin Ikegami, Takeshi Kanki, Hideaki Nishiyama, Kumiko Beck, Goichi Gon, Yasufumi Okazaki, Shuhei Todo, Kenichi Tamura, Atsushi Tsukita, Sachiko Mochizuki, Hideki |
author_facet | Sugiyama, Shintaro Sasaki, Tsutomu Tanaka, Hiroo Yan, Haomin Ikegami, Takeshi Kanki, Hideaki Nishiyama, Kumiko Beck, Goichi Gon, Yasufumi Okazaki, Shuhei Todo, Kenichi Tamura, Atsushi Tsukita, Sachiko Mochizuki, Hideki |
author_sort | Sugiyama, Shintaro |
collection | PubMed |
description | Blood–brain barrier (BBB) disruption contributes to brain injury and neurological impairment. Tight junctions (TJs) and cell–cell adhesion complexes develop between endothelial cells in the brain to establish and maintain the BBB. Occludin, the first transmembrane protein identified in TJs, has received intense research interest because numerous in vitro studies have suggested its importance in maintaining BBB integrity. However, its role in maintaining BBB integrity after ischemic stroke is less clear owing to the lack of in vivo evidence. This study aimed to investigate the dynamics and function of occludin across the acute and chronic phases after stroke using occludin-deficient mice. By photochemically induced thrombosis model, the expression of occludin was decreased in brain endothelial cells from ischemic lesions. The neurological function of occludin-deficient mice was continuously impaired compared to that of wild-type mice. BBB integrity evaluated by Evans blue and 0.5-kDa fluorescein in the acute phase and by 10-kDa fluorescein isothiocyanate-labeled dextran in the chronic phase was decreased to a greater extent after stroke in occludin-deficient mice. Furthermore, occludin-deficient mice showed decreased claudin-5 and neovascularization after stroke. Our study reveals that occludin plays an important role from the acute to the chronic phase after ischemic stroke in vivo. |
format | Online Article Text |
id | pubmed-9938878 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-99388782023-02-20 The tight junction protein occludin modulates blood–brain barrier integrity and neurological function after ischemic stroke in mice Sugiyama, Shintaro Sasaki, Tsutomu Tanaka, Hiroo Yan, Haomin Ikegami, Takeshi Kanki, Hideaki Nishiyama, Kumiko Beck, Goichi Gon, Yasufumi Okazaki, Shuhei Todo, Kenichi Tamura, Atsushi Tsukita, Sachiko Mochizuki, Hideki Sci Rep Article Blood–brain barrier (BBB) disruption contributes to brain injury and neurological impairment. Tight junctions (TJs) and cell–cell adhesion complexes develop between endothelial cells in the brain to establish and maintain the BBB. Occludin, the first transmembrane protein identified in TJs, has received intense research interest because numerous in vitro studies have suggested its importance in maintaining BBB integrity. However, its role in maintaining BBB integrity after ischemic stroke is less clear owing to the lack of in vivo evidence. This study aimed to investigate the dynamics and function of occludin across the acute and chronic phases after stroke using occludin-deficient mice. By photochemically induced thrombosis model, the expression of occludin was decreased in brain endothelial cells from ischemic lesions. The neurological function of occludin-deficient mice was continuously impaired compared to that of wild-type mice. BBB integrity evaluated by Evans blue and 0.5-kDa fluorescein in the acute phase and by 10-kDa fluorescein isothiocyanate-labeled dextran in the chronic phase was decreased to a greater extent after stroke in occludin-deficient mice. Furthermore, occludin-deficient mice showed decreased claudin-5 and neovascularization after stroke. Our study reveals that occludin plays an important role from the acute to the chronic phase after ischemic stroke in vivo. Nature Publishing Group UK 2023-02-18 /pmc/articles/PMC9938878/ /pubmed/36806348 http://dx.doi.org/10.1038/s41598-023-29894-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Sugiyama, Shintaro Sasaki, Tsutomu Tanaka, Hiroo Yan, Haomin Ikegami, Takeshi Kanki, Hideaki Nishiyama, Kumiko Beck, Goichi Gon, Yasufumi Okazaki, Shuhei Todo, Kenichi Tamura, Atsushi Tsukita, Sachiko Mochizuki, Hideki The tight junction protein occludin modulates blood–brain barrier integrity and neurological function after ischemic stroke in mice |
title | The tight junction protein occludin modulates blood–brain barrier integrity and neurological function after ischemic stroke in mice |
title_full | The tight junction protein occludin modulates blood–brain barrier integrity and neurological function after ischemic stroke in mice |
title_fullStr | The tight junction protein occludin modulates blood–brain barrier integrity and neurological function after ischemic stroke in mice |
title_full_unstemmed | The tight junction protein occludin modulates blood–brain barrier integrity and neurological function after ischemic stroke in mice |
title_short | The tight junction protein occludin modulates blood–brain barrier integrity and neurological function after ischemic stroke in mice |
title_sort | tight junction protein occludin modulates blood–brain barrier integrity and neurological function after ischemic stroke in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9938878/ https://www.ncbi.nlm.nih.gov/pubmed/36806348 http://dx.doi.org/10.1038/s41598-023-29894-1 |
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