AER-271 在 tMCAO 小鼠模型中的神经保护作用:自噬、细胞凋亡和炎症的调节作用

IF 4.5 2区 医学 Q2 CELL BIOLOGY Inflammation Pub Date : 2024-08-09 DOI:10.1007/s10753-024-02082-7
Shenglong Mo, Chengmin Yang, Xingwu Zheng, Hui Lv, Sanyin Mao, Ning Liu, Qin Yang, Bao Liao, Meiling Yang, Zhicheng Lu, Lina Tang, Xiaorui Huang, Chongdong Jian, Xuebin Li, Jingwei Shang
{"title":"AER-271 在 tMCAO 小鼠模型中的神经保护作用:自噬、细胞凋亡和炎症的调节作用","authors":"Shenglong Mo, Chengmin Yang, Xingwu Zheng, Hui Lv, Sanyin Mao, Ning Liu, Qin Yang, Bao Liao, Meiling Yang, Zhicheng Lu, Lina Tang, Xiaorui Huang, Chongdong Jian, Xuebin Li, Jingwei Shang","doi":"10.1007/s10753-024-02082-7","DOIUrl":null,"url":null,"abstract":"<p><p>Following ischemic stroke, aquaporin 4 (AQP4) expression modifications have been associated with increased inflammation. However, the underlying mechanisms are not fully understood. This study aims to elucidate the mechanistic basis of post-cerebral ischemia-reperfusion (I/R) inflammation by employing the AQP4-specific inhibitor, AER-271. The middle cerebral artery occlusion (MCAO) model was used to induce ischemic stroke in mice. C57BL/6 mice were randomly allocated into four groups: sham operation, I/R, AER-271, and 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) treatment, with observations recorded at 1 day, 3 days, and 7 days post-tMCAO. Each group consisted of 15 mice. Procedures included histological examination through HE staining, neurological scoring, Western blot analysis, and immunofluorescence staining. AER-271 treatment yielded significant improvements in post-stroke weight recovery and neurological scores, accompanied by a reduction in cerebral infarction volume. Moreover, AER-271 exhibited a noticeable influence on autophagic and apoptotic pathways, affecting the activation of both pro-inflammatory and anti-inflammatory cytokines. Alterations in the levels of inflammatory biomarkers MCP-1, NLRP3, and caspase 1 were also detected. Finally, a comparative assessment of the effects of AER-271 and TGN-020 in mitigating apoptosis and microglial polarization in ischemic mice revealed neuroprotective effects with no significant difference in efficacy. This study provides essential insights into the neuroprotective mechanisms of AER-271 in cerebral ischemia-reperfusion injury, offering potential clinical applications in the treatment of ischemic cerebrovascular disorders.</p>","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Neuroprotective Effects of AER-271 in a tMCAO Mouse Model: Modulation of Autophagy, Apoptosis, and Inflammation.\",\"authors\":\"Shenglong Mo, Chengmin Yang, Xingwu Zheng, Hui Lv, Sanyin Mao, Ning Liu, Qin Yang, Bao Liao, Meiling Yang, Zhicheng Lu, Lina Tang, Xiaorui Huang, Chongdong Jian, Xuebin Li, Jingwei Shang\",\"doi\":\"10.1007/s10753-024-02082-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Following ischemic stroke, aquaporin 4 (AQP4) expression modifications have been associated with increased inflammation. However, the underlying mechanisms are not fully understood. This study aims to elucidate the mechanistic basis of post-cerebral ischemia-reperfusion (I/R) inflammation by employing the AQP4-specific inhibitor, AER-271. The middle cerebral artery occlusion (MCAO) model was used to induce ischemic stroke in mice. C57BL/6 mice were randomly allocated into four groups: sham operation, I/R, AER-271, and 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) treatment, with observations recorded at 1 day, 3 days, and 7 days post-tMCAO. Each group consisted of 15 mice. Procedures included histological examination through HE staining, neurological scoring, Western blot analysis, and immunofluorescence staining. AER-271 treatment yielded significant improvements in post-stroke weight recovery and neurological scores, accompanied by a reduction in cerebral infarction volume. Moreover, AER-271 exhibited a noticeable influence on autophagic and apoptotic pathways, affecting the activation of both pro-inflammatory and anti-inflammatory cytokines. Alterations in the levels of inflammatory biomarkers MCP-1, NLRP3, and caspase 1 were also detected. Finally, a comparative assessment of the effects of AER-271 and TGN-020 in mitigating apoptosis and microglial polarization in ischemic mice revealed neuroprotective effects with no significant difference in efficacy. This study provides essential insights into the neuroprotective mechanisms of AER-271 in cerebral ischemia-reperfusion injury, offering potential clinical applications in the treatment of ischemic cerebrovascular disorders.</p>\",\"PeriodicalId\":13524,\"journal\":{\"name\":\"Inflammation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-08-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Inflammation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10753-024-02082-7\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Inflammation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10753-024-02082-7","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

缺血性中风后,水通道蛋白 4(AQP4)表达的改变与炎症的加剧有关。然而,其潜在机制尚未完全明了。本研究旨在通过使用 AQP4 特异性抑制剂 AER-271 来阐明脑缺血再灌注(I/R)后炎症的机制基础。采用大脑中动脉闭塞(MCAO)模型诱导小鼠缺血性中风。将C57BL/6小鼠随机分为四组:假手术组、I/R组、AER-271组和2-(烟酰胺)-1,3,4-噻二唑(TGN-020)治疗组,分别记录MCAO后1天、3天和7天的观察结果。每组 15 只小鼠。研究程序包括通过 HE 染色进行组织学检查、神经系统评分、Western 印迹分析和免疫荧光染色。AER-271治疗显著改善了中风后体重恢复和神经系统评分,同时减少了脑梗塞体积。此外,AER-271 还对自噬和凋亡途径产生了明显的影响,并影响了促炎和抗炎细胞因子的激活。此外,还检测到炎症生物标志物 MCP-1、NLRP3 和 caspase 1 水平的变化。最后,通过比较评估 AER-271 和 TGN-020 在减轻缺血小鼠细胞凋亡和小胶质细胞极化方面的作用,发现这两种药物具有神经保护作用,且疗效无显著差异。这项研究为了解 AER-271 在脑缺血再灌注损伤中的神经保护机制提供了重要依据,为缺血性脑血管疾病的治疗提供了潜在的临床应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

摘要图片

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Neuroprotective Effects of AER-271 in a tMCAO Mouse Model: Modulation of Autophagy, Apoptosis, and Inflammation.

Following ischemic stroke, aquaporin 4 (AQP4) expression modifications have been associated with increased inflammation. However, the underlying mechanisms are not fully understood. This study aims to elucidate the mechanistic basis of post-cerebral ischemia-reperfusion (I/R) inflammation by employing the AQP4-specific inhibitor, AER-271. The middle cerebral artery occlusion (MCAO) model was used to induce ischemic stroke in mice. C57BL/6 mice were randomly allocated into four groups: sham operation, I/R, AER-271, and 2-(nicotinamide)-1,3,4-thiadiazole (TGN-020) treatment, with observations recorded at 1 day, 3 days, and 7 days post-tMCAO. Each group consisted of 15 mice. Procedures included histological examination through HE staining, neurological scoring, Western blot analysis, and immunofluorescence staining. AER-271 treatment yielded significant improvements in post-stroke weight recovery and neurological scores, accompanied by a reduction in cerebral infarction volume. Moreover, AER-271 exhibited a noticeable influence on autophagic and apoptotic pathways, affecting the activation of both pro-inflammatory and anti-inflammatory cytokines. Alterations in the levels of inflammatory biomarkers MCP-1, NLRP3, and caspase 1 were also detected. Finally, a comparative assessment of the effects of AER-271 and TGN-020 in mitigating apoptosis and microglial polarization in ischemic mice revealed neuroprotective effects with no significant difference in efficacy. This study provides essential insights into the neuroprotective mechanisms of AER-271 in cerebral ischemia-reperfusion injury, offering potential clinical applications in the treatment of ischemic cerebrovascular disorders.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Inflammation
Inflammation 医学-免疫学
CiteScore
9.70
自引率
0.00%
发文量
168
审稿时长
3.0 months
期刊介绍: Inflammation publishes the latest international advances in experimental and clinical research on the physiology, biochemistry, cell biology, and pharmacology of inflammation. Contributions include full-length scientific reports, short definitive articles, and papers from meetings and symposia proceedings. The journal''s coverage includes acute and chronic inflammation; mediators of inflammation; mechanisms of tissue injury and cytotoxicity; pharmacology of inflammation; and clinical studies of inflammation and its modification.
期刊最新文献
Inhibition of GDNF-Driven Macrophage-to-Myofibroblast Transition Protects Against Colitis-Associated Intestinal Fibrosis. USP30-AS1 Suppresses Colon Cancer Cell Inflammatory Response Through NF-κB/MYBBP1A Signaling. GZMK Facilitates Experimental Rheumatoid Arthritis Progression by Interacting with CCL5 and Activating the ERK Signaling. Multiple Machine Learning Identifies Key Gene PHLDA1 Suppressing NAFLD Progression. Acetyl 11-Keto Beta-Boswellic Acid Improves Neurological Functions in a Mouse Model of Multiple Sclerosis.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1