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Pharmacological inhibition of TLR4-NOX4 signal protects against neuronal death in transient focal ischemia
Recent data have shown that TLR4 performs a key role in cerebral ischemia-reperfusion injury which serves as the origin of the immunological inflammatory reactions. However, the therapeutic effects of pharmacological inhibitions of TLR4 and its immediate down-stream pathway remain to be uncovered. I...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508453/ https://www.ncbi.nlm.nih.gov/pubmed/23193438 http://dx.doi.org/10.1038/srep00896 |
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author | Suzuki, Yukiya Hattori, Kozo Hamanaka, Junya Murase, Tetsuji Egashira, Yusuke Mishiro, Keisuke Ishiguro, Mitsunori Tsuruma, Kazuhiro Hirose, Yoshinobu Tanaka, Hiroyuki Yoshimura, Shinichi Shimazawa, Masamitsu Inagaki, Naoki Nagasawa, Hideko Iwama, Toru Hara, Hideaki |
author_facet | Suzuki, Yukiya Hattori, Kozo Hamanaka, Junya Murase, Tetsuji Egashira, Yusuke Mishiro, Keisuke Ishiguro, Mitsunori Tsuruma, Kazuhiro Hirose, Yoshinobu Tanaka, Hiroyuki Yoshimura, Shinichi Shimazawa, Masamitsu Inagaki, Naoki Nagasawa, Hideko Iwama, Toru Hara, Hideaki |
author_sort | Suzuki, Yukiya |
collection | PubMed |
description | Recent data have shown that TLR4 performs a key role in cerebral ischemia-reperfusion injury which serves as the origin of the immunological inflammatory reactions. However, the therapeutic effects of pharmacological inhibitions of TLR4 and its immediate down-stream pathway remain to be uncovered. In the present study, on mice, intracerebroventricular injection of resatorvid (TLR4 signal inhibitor; 0.01 μg) significantly reduced infarct volume and improved neurological score after middle cerebral artery occlusion and reperfusion. The levels of phospho-p38, nuclear factor-kappa B, and matrix metalloproteinase 9 expressions were significantly suppressed in the resatorvid-treated group. In addition, NOX4 associates with TLR4 after cerebral ischemia-reperfusion seen in mice and human. Genetic and pharmacological inhibitions of TLR4 each reduced NOX4 expression, leading to suppression of oxidative/nitrative stress and of neuronal apoptosis. These data suggest that resatorvid has potential as a therapeutic agent for stroke since it inhibits TLR4-NOX4 signaling which may be the predominant causal pathway. |
format | Online Article Text |
id | pubmed-3508453 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-35084532012-11-28 Pharmacological inhibition of TLR4-NOX4 signal protects against neuronal death in transient focal ischemia Suzuki, Yukiya Hattori, Kozo Hamanaka, Junya Murase, Tetsuji Egashira, Yusuke Mishiro, Keisuke Ishiguro, Mitsunori Tsuruma, Kazuhiro Hirose, Yoshinobu Tanaka, Hiroyuki Yoshimura, Shinichi Shimazawa, Masamitsu Inagaki, Naoki Nagasawa, Hideko Iwama, Toru Hara, Hideaki Sci Rep Article Recent data have shown that TLR4 performs a key role in cerebral ischemia-reperfusion injury which serves as the origin of the immunological inflammatory reactions. However, the therapeutic effects of pharmacological inhibitions of TLR4 and its immediate down-stream pathway remain to be uncovered. In the present study, on mice, intracerebroventricular injection of resatorvid (TLR4 signal inhibitor; 0.01 μg) significantly reduced infarct volume and improved neurological score after middle cerebral artery occlusion and reperfusion. The levels of phospho-p38, nuclear factor-kappa B, and matrix metalloproteinase 9 expressions were significantly suppressed in the resatorvid-treated group. In addition, NOX4 associates with TLR4 after cerebral ischemia-reperfusion seen in mice and human. Genetic and pharmacological inhibitions of TLR4 each reduced NOX4 expression, leading to suppression of oxidative/nitrative stress and of neuronal apoptosis. These data suggest that resatorvid has potential as a therapeutic agent for stroke since it inhibits TLR4-NOX4 signaling which may be the predominant causal pathway. Nature Publishing Group 2012-11-28 /pmc/articles/PMC3508453/ /pubmed/23193438 http://dx.doi.org/10.1038/srep00896 Text en Copyright © 2012, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareALike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ |
spellingShingle | Article Suzuki, Yukiya Hattori, Kozo Hamanaka, Junya Murase, Tetsuji Egashira, Yusuke Mishiro, Keisuke Ishiguro, Mitsunori Tsuruma, Kazuhiro Hirose, Yoshinobu Tanaka, Hiroyuki Yoshimura, Shinichi Shimazawa, Masamitsu Inagaki, Naoki Nagasawa, Hideko Iwama, Toru Hara, Hideaki Pharmacological inhibition of TLR4-NOX4 signal protects against neuronal death in transient focal ischemia |
title | Pharmacological inhibition of TLR4-NOX4 signal protects against neuronal death in transient focal ischemia |
title_full | Pharmacological inhibition of TLR4-NOX4 signal protects against neuronal death in transient focal ischemia |
title_fullStr | Pharmacological inhibition of TLR4-NOX4 signal protects against neuronal death in transient focal ischemia |
title_full_unstemmed | Pharmacological inhibition of TLR4-NOX4 signal protects against neuronal death in transient focal ischemia |
title_short | Pharmacological inhibition of TLR4-NOX4 signal protects against neuronal death in transient focal ischemia |
title_sort | pharmacological inhibition of tlr4-nox4 signal protects against neuronal death in transient focal ischemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508453/ https://www.ncbi.nlm.nih.gov/pubmed/23193438 http://dx.doi.org/10.1038/srep00896 |
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