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Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury

Notch signaling pathway is involved in many physiological and pathological processes. The γ-secretase inhibitor DAPT inhibits Notch signaling pathway and promotes nerve regeneration after cerebral ischemia. However, neuroprotective effects of DAPT against acute craniocerebral injury remain unclear....

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Detalles Bibliográficos
Autores principales: Zhang, Hong-Mei, Liu, Pei, Jiang, Cheng, Jin, Xiao-Qing, Liu, Rui-Ning, Li, Shun-Qing, Zhao, Yan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814062/
https://www.ncbi.nlm.nih.gov/pubmed/29447233
http://dx.doi.org/10.1371/journal.pone.0193037
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author Zhang, Hong-Mei
Liu, Pei
Jiang, Cheng
Jin, Xiao-Qing
Liu, Rui-Ning
Li, Shun-Qing
Zhao, Yan
author_facet Zhang, Hong-Mei
Liu, Pei
Jiang, Cheng
Jin, Xiao-Qing
Liu, Rui-Ning
Li, Shun-Qing
Zhao, Yan
author_sort Zhang, Hong-Mei
collection PubMed
description Notch signaling pathway is involved in many physiological and pathological processes. The γ-secretase inhibitor DAPT inhibits Notch signaling pathway and promotes nerve regeneration after cerebral ischemia. However, neuroprotective effects of DAPT against acute craniocerebral injury remain unclear. In this study, we established rat model of acute craniocerebral injury, and found that with the increase of damage grade, the expression of Notch and downstream protein Hes1 and Hes5 expression gradually increased. After the administration of DAPT, the expression of Notch, Hes1 and Hes5 was inhibited, apoptosis and oxidative stress decreased, neurological function and cognitive function improved. These results suggest that Notch signaling can be used as an indicator to assess the severity of post-traumatic brain injury. Notch inhibitor DAPT can reduce oxidative stress and apoptosis after acute craniocerebral injury, and is a potential drug for the treatment of acute craniocerebral injury.
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spelling pubmed-58140622018-03-02 Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury Zhang, Hong-Mei Liu, Pei Jiang, Cheng Jin, Xiao-Qing Liu, Rui-Ning Li, Shun-Qing Zhao, Yan PLoS One Research Article Notch signaling pathway is involved in many physiological and pathological processes. The γ-secretase inhibitor DAPT inhibits Notch signaling pathway and promotes nerve regeneration after cerebral ischemia. However, neuroprotective effects of DAPT against acute craniocerebral injury remain unclear. In this study, we established rat model of acute craniocerebral injury, and found that with the increase of damage grade, the expression of Notch and downstream protein Hes1 and Hes5 expression gradually increased. After the administration of DAPT, the expression of Notch, Hes1 and Hes5 was inhibited, apoptosis and oxidative stress decreased, neurological function and cognitive function improved. These results suggest that Notch signaling can be used as an indicator to assess the severity of post-traumatic brain injury. Notch inhibitor DAPT can reduce oxidative stress and apoptosis after acute craniocerebral injury, and is a potential drug for the treatment of acute craniocerebral injury. Public Library of Science 2018-02-15 /pmc/articles/PMC5814062/ /pubmed/29447233 http://dx.doi.org/10.1371/journal.pone.0193037 Text en © 2018 Zhang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Zhang, Hong-Mei
Liu, Pei
Jiang, Cheng
Jin, Xiao-Qing
Liu, Rui-Ning
Li, Shun-Qing
Zhao, Yan
Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury
title Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury
title_full Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury
title_fullStr Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury
title_full_unstemmed Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury
title_short Notch signaling inhibitor DAPT provides protection against acute craniocerebral injury
title_sort notch signaling inhibitor dapt provides protection against acute craniocerebral injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5814062/
https://www.ncbi.nlm.nih.gov/pubmed/29447233
http://dx.doi.org/10.1371/journal.pone.0193037
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