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Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats
Previous studies have shown neuroprotective effects of hypothermia. However, its effects on subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) remain unclear. In this study, a SAH rat model was employed to study the effects and mechanisms of pramipexole-induced hypothermia on EBI after S...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812308/ https://www.ncbi.nlm.nih.gov/pubmed/27026509 http://dx.doi.org/10.1038/srep23817 |
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author | Ma, Junwei Wang, Zhong Liu, Chenglin Shen, Haitao Chen, Zhouqing Yin, Jia Zuo, Gang Duan, Xiaochun Li, Haiying Chen, Gang |
author_facet | Ma, Junwei Wang, Zhong Liu, Chenglin Shen, Haitao Chen, Zhouqing Yin, Jia Zuo, Gang Duan, Xiaochun Li, Haiying Chen, Gang |
author_sort | Ma, Junwei |
collection | PubMed |
description | Previous studies have shown neuroprotective effects of hypothermia. However, its effects on subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) remain unclear. In this study, a SAH rat model was employed to study the effects and mechanisms of pramipexole-induced hypothermia on EBI after SAH. Dose-response experiments were performed to select the appropriate pramipexole concentration and frequency of administration for induction of mild hypothermia (33–36 °C). Western blot, neurobehavioral evaluation, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade B (FJB) staining were used to detect the effects of pramipexole-induced hypothermia on SAH-induced EBI, as well as to study whether controlled rewarming could attenuate these effects. Inhibitors targeting the PI3K/AKT/GSK3β pathway were administered to determine whether the neuroprotective effect of pramipexole-induced hypothermia was mediated by PI3K/AKT/GSK3β signaling pathway. The results showed that intraperitoneal injection of pramipexole at 0.25 mg/kg body weight once per 8 hours was found to successfully and safely maintain rats at mild hypothermia. Pramipexole-induced hypothermia ameliorated SAH-induced brain cell death, blood-brain barrier damage and neurobehavioral deficits in a PI3K/AKT/GSK3β signaling-dependent manner. Therefore, we may conclude that pramipexole-induced hypothermia could effectively inhibit EBI after SAH in rats via PI3K/AKT/GSK3β signaling pathway. |
format | Online Article Text |
id | pubmed-4812308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48123082016-04-04 Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats Ma, Junwei Wang, Zhong Liu, Chenglin Shen, Haitao Chen, Zhouqing Yin, Jia Zuo, Gang Duan, Xiaochun Li, Haiying Chen, Gang Sci Rep Article Previous studies have shown neuroprotective effects of hypothermia. However, its effects on subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) remain unclear. In this study, a SAH rat model was employed to study the effects and mechanisms of pramipexole-induced hypothermia on EBI after SAH. Dose-response experiments were performed to select the appropriate pramipexole concentration and frequency of administration for induction of mild hypothermia (33–36 °C). Western blot, neurobehavioral evaluation, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade B (FJB) staining were used to detect the effects of pramipexole-induced hypothermia on SAH-induced EBI, as well as to study whether controlled rewarming could attenuate these effects. Inhibitors targeting the PI3K/AKT/GSK3β pathway were administered to determine whether the neuroprotective effect of pramipexole-induced hypothermia was mediated by PI3K/AKT/GSK3β signaling pathway. The results showed that intraperitoneal injection of pramipexole at 0.25 mg/kg body weight once per 8 hours was found to successfully and safely maintain rats at mild hypothermia. Pramipexole-induced hypothermia ameliorated SAH-induced brain cell death, blood-brain barrier damage and neurobehavioral deficits in a PI3K/AKT/GSK3β signaling-dependent manner. Therefore, we may conclude that pramipexole-induced hypothermia could effectively inhibit EBI after SAH in rats via PI3K/AKT/GSK3β signaling pathway. Nature Publishing Group 2016-03-30 /pmc/articles/PMC4812308/ /pubmed/27026509 http://dx.doi.org/10.1038/srep23817 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Ma, Junwei Wang, Zhong Liu, Chenglin Shen, Haitao Chen, Zhouqing Yin, Jia Zuo, Gang Duan, Xiaochun Li, Haiying Chen, Gang Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats |
title | Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats |
title_full | Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats |
title_fullStr | Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats |
title_full_unstemmed | Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats |
title_short | Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats |
title_sort | pramipexole-induced hypothermia reduces early brain injury via pi3k/akt/gsk3β pathway in subarachnoid hemorrhage rats |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812308/ https://www.ncbi.nlm.nih.gov/pubmed/27026509 http://dx.doi.org/10.1038/srep23817 |
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