Phenothiazine Confers Neuroprotection via Dpp2/7 in High Altitude Traumatic Brain Injury Mouse Model.

IF 1.6 4区 医学 Q4 BIOPHYSICS
Wenxin Zhang, Yuting Yang, Jing Guo, Fei Hu, Yuan Ma, Qing Ouyang
{"title":"Phenothiazine Confers Neuroprotection via Dpp2/7 in High Altitude Traumatic Brain Injury Mouse Model.","authors":"Wenxin Zhang, Yuting Yang, Jing Guo, Fei Hu, Yuan Ma, Qing Ouyang","doi":"10.1089/ham.2024.0096","DOIUrl":null,"url":null,"abstract":"<p><p>Zhang, Wenxin, Yuting Yang, Jing Guo, Fei Hu, Yuan Ma, and Qing Ouyang. Phenothiazine confers neuroprotection via Dpp2/7 in high altitude traumatic brain injury mouse model. <i>High Alt Med Biol.</i> 00:00-00, 2025. <b><i>Background:</i></b> Traumatic brain injury (TBI) in high altitude areas can lead to more severe cerebral edema, higher disability, and mortality than in low altitude areas. This study was designed to evaluate the neuroprotective effects and underlying mechanisms of phenothiazine on TBI at high altitudes. <b><i>Methods:</i></b> Mice were kept in a hypobaric chamber for 7 days under simulated conditions of 5,000 m above sea level. A controlled cortical impact (CCI) model was established and followed by phenothiazine (chlorpromazine and promethazine) and Dpp2/7 inhibitor UAMC00039 treatment. Hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), western blot, label-free quantitative proteomics, and real-time quantitative polymerase chain reaction (RT-qPCR) assays were performed to assess the effects of phenothiazine and UAMC00039 on TBI. <b><i>Results:</i></b> HE staining confirmed that phenothiazine treatment could ameliorate CCI-induced brain injury. IHC, western blot, and RT-qPCR showed that cell apoptosis was alleviated by phenothiazine after high altitude TBI, as proved by the reduction of cleaved-Caspase-3 and increased Bcl-2 expression. Label-free quantitative proteomics, IHC, and western blot showed that phenothiazine significantly upregulated Dpp2/7 after high altitude TBI. Western blot and IHC showed that UAMC00039 treatment significantly reversed phenothiazine-mediated Bcl-2 upregulation and cleaved-Caspase-3 downregulation after high altitude TBI. <b><i>Conclusions:</i></b> The results indicated that phenothiazine offers neuroprotective effects via antiapoptosis after high altitude TBI, and this protective mechanism is associated with Dpp2/7-mediated Bcl-2 expression and Caspase-3 cleaving.</p>","PeriodicalId":12975,"journal":{"name":"High altitude medicine & biology","volume":" ","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"High altitude medicine & biology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/ham.2024.0096","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOPHYSICS","Score":null,"Total":0}
引用次数: 0

Abstract

Zhang, Wenxin, Yuting Yang, Jing Guo, Fei Hu, Yuan Ma, and Qing Ouyang. Phenothiazine confers neuroprotection via Dpp2/7 in high altitude traumatic brain injury mouse model. High Alt Med Biol. 00:00-00, 2025. Background: Traumatic brain injury (TBI) in high altitude areas can lead to more severe cerebral edema, higher disability, and mortality than in low altitude areas. This study was designed to evaluate the neuroprotective effects and underlying mechanisms of phenothiazine on TBI at high altitudes. Methods: Mice were kept in a hypobaric chamber for 7 days under simulated conditions of 5,000 m above sea level. A controlled cortical impact (CCI) model was established and followed by phenothiazine (chlorpromazine and promethazine) and Dpp2/7 inhibitor UAMC00039 treatment. Hematoxylin-eosin (HE) staining, immunohistochemistry (IHC), western blot, label-free quantitative proteomics, and real-time quantitative polymerase chain reaction (RT-qPCR) assays were performed to assess the effects of phenothiazine and UAMC00039 on TBI. Results: HE staining confirmed that phenothiazine treatment could ameliorate CCI-induced brain injury. IHC, western blot, and RT-qPCR showed that cell apoptosis was alleviated by phenothiazine after high altitude TBI, as proved by the reduction of cleaved-Caspase-3 and increased Bcl-2 expression. Label-free quantitative proteomics, IHC, and western blot showed that phenothiazine significantly upregulated Dpp2/7 after high altitude TBI. Western blot and IHC showed that UAMC00039 treatment significantly reversed phenothiazine-mediated Bcl-2 upregulation and cleaved-Caspase-3 downregulation after high altitude TBI. Conclusions: The results indicated that phenothiazine offers neuroprotective effects via antiapoptosis after high altitude TBI, and this protective mechanism is associated with Dpp2/7-mediated Bcl-2 expression and Caspase-3 cleaving.

吩噻嗪通过Dpp2/7对高原创伤性脑损伤小鼠模型的神经保护作用
张文欣,杨玉婷,郭静,胡飞,马元,欧阳青。吩噻嗪通过Dpp2/7对高原创伤性脑损伤小鼠模型具有神经保护作用。高Alt医学生物杂志,200,2025。背景:与低海拔地区相比,高海拔地区的创伤性脑损伤(TBI)可导致更严重的脑水肿、更高的残疾和死亡率。本研究旨在评估吩噻嗪对高原创伤性脑损伤的神经保护作用及其潜在机制。方法:在模拟海拔5000 m的条件下,将小鼠置于低压舱中7 d。建立控制性皮质冲击(CCI)模型,然后给予吩噻嗪(氯丙嗪和异丙嗪)和Dpp2/7抑制剂UAMC00039治疗。采用苏木精-伊红(HE)染色、免疫组化(IHC)、western blot、无标记定量蛋白质组学、实时定量聚合酶链反应(RT-qPCR)等方法评估吩噻嗪和UAMC00039对TBI的影响。结果:HE染色证实吩噻嗪治疗可改善cci所致脑损伤。免疫组化、western blot和RT-qPCR结果显示,吩噻嗪可减轻高原TBI后的细胞凋亡,其表现为cleaved-Caspase-3的减少和Bcl-2表达的增加。无标记定量蛋白质组学、免疫组化和western blot显示,吩噻嗪显著上调高原创伤后Dpp2/7。Western blot和免疫组化结果显示,UAMC00039处理显著逆转了吩噻嗪介导的Bcl-2上调和cleaved-Caspase-3下调。结论:吩噻嗪通过抗高原脑外伤后细胞凋亡发挥神经保护作用,其机制与dpp2 /7介导的Bcl-2表达和Caspase-3切割有关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
High altitude medicine & biology
High altitude medicine & biology 医学-公共卫生、环境卫生与职业卫生
CiteScore
3.80
自引率
9.50%
发文量
44
审稿时长
>12 weeks
期刊介绍: High Altitude Medicine & Biology is the only peer-reviewed journal covering the medical and biological issues that impact human life at high altitudes. The Journal delivers critical findings on the impact of high altitude on lung and heart disease, appetite and weight loss, pulmonary and cerebral edema, hypertension, dehydration, infertility, and other diseases. It covers the full spectrum of high altitude life sciences from pathology to human and animal ecology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信