Dexmedetomidine protects against cerebral ischemia-reperfusion injury in mice by interfering with the crosstalk between autophagy and ferroptosis.

IF 1.5 4区 医学 Q3 CLINICAL NEUROLOGY
Cong Luo, Yi Ou, Yujie Xu, Fengxian Yu
{"title":"Dexmedetomidine protects against cerebral ischemia-reperfusion injury in mice by interfering with the crosstalk between autophagy and ferroptosis.","authors":"Cong Luo, Yi Ou, Yujie Xu, Fengxian Yu","doi":"10.1080/01616412.2025.2524741","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Previous studies show DEX protects against focal cerebral ischemia by hindering autophagy. However, the exact mechanisms are unclear. This study hypothesizes DEX may protect neurons by regulating the crosstalk between autophagy and ferroptosis.</p><p><strong>Methods: </strong>In this study, male C57/BL6 mice were used in an MCAO model divided into five groups. After MCAO and reperfusion, treatments with DEX, DEX+Erastin, or DEX+rapamycin were administered. Neurological deficits and cerebral infarction volumes were measured 24 hours later. Electron microscopy and molecular techniques were used to analyze autophagy and ferroptosis markers to explore DEX's neuroprotective mechanism.</p><p><strong>Results: </strong>Compared to sham controls, the model group showed significantly increased cerebral infarction volume and neurobehavioral scores (<i>p</i> < 0.05). DEX treatment reversed these effects, demonstrating neuroprotection against ischemic injury. Simultaneously, DEX treatment safeguards mitochondrial integrity by suppressing autophagy lysosomes. It also upregulates the expression of glutathione (GSH) protein, solute carrier family 7 member 11 (SLC7A11) protein, and glutathione peroxidase 4 (GPX4). Moreover, DEX inhibits the levels of malondialdehyde (MDA), ferrous ion (Fe2+), microtubule-associated protein 1A/1B-light chain 3 (LC3), and Beclin1 proteins (all <i>p</i> values < 0.05), thereby intervening in the crosstalk between the autophagy and ferroptosis pathways and ultimately exerting its neuroprotective function. Notably, DEX's effects were negated by ferroptosis inducer Erastin or autophagy inducer RAPA.</p><p><strong>Conclusion: </strong>Dexmedetomidine modulates the crosstalk between autophagy and ferroptosis pathways, thereby protecting the mouse brain against ischemia-reperfusion injury and providing novel insights for the future treatment of ischemic stroke.</p>","PeriodicalId":19131,"journal":{"name":"Neurological Research","volume":" ","pages":"1-12"},"PeriodicalIF":1.5000,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurological Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/01616412.2025.2524741","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Objective: Previous studies show DEX protects against focal cerebral ischemia by hindering autophagy. However, the exact mechanisms are unclear. This study hypothesizes DEX may protect neurons by regulating the crosstalk between autophagy and ferroptosis.

Methods: In this study, male C57/BL6 mice were used in an MCAO model divided into five groups. After MCAO and reperfusion, treatments with DEX, DEX+Erastin, or DEX+rapamycin were administered. Neurological deficits and cerebral infarction volumes were measured 24 hours later. Electron microscopy and molecular techniques were used to analyze autophagy and ferroptosis markers to explore DEX's neuroprotective mechanism.

Results: Compared to sham controls, the model group showed significantly increased cerebral infarction volume and neurobehavioral scores (p < 0.05). DEX treatment reversed these effects, demonstrating neuroprotection against ischemic injury. Simultaneously, DEX treatment safeguards mitochondrial integrity by suppressing autophagy lysosomes. It also upregulates the expression of glutathione (GSH) protein, solute carrier family 7 member 11 (SLC7A11) protein, and glutathione peroxidase 4 (GPX4). Moreover, DEX inhibits the levels of malondialdehyde (MDA), ferrous ion (Fe2+), microtubule-associated protein 1A/1B-light chain 3 (LC3), and Beclin1 proteins (all p values < 0.05), thereby intervening in the crosstalk between the autophagy and ferroptosis pathways and ultimately exerting its neuroprotective function. Notably, DEX's effects were negated by ferroptosis inducer Erastin or autophagy inducer RAPA.

Conclusion: Dexmedetomidine modulates the crosstalk between autophagy and ferroptosis pathways, thereby protecting the mouse brain against ischemia-reperfusion injury and providing novel insights for the future treatment of ischemic stroke.

右美托咪定通过干扰自噬和铁下垂之间的串扰,对小鼠脑缺血再灌注损伤具有保护作用。
目的:已有研究表明右美托咪唑通过抑制脑自噬来保护局灶性脑缺血。然而,确切的机制尚不清楚。本研究推测DEX可能通过调节自噬和铁下垂之间的串扰来保护神经元。方法:采用雄性C57/BL6小鼠建立MCAO模型,分为5组。MCAO和再灌注后,给予DEX、DEX+Erastin或DEX+雷帕霉素治疗。24小时后测量神经功能缺损和脑梗死体积。利用电镜和分子技术分析自噬和铁下垂标志物,探讨DEX的神经保护机制。结果:与假对照组相比,模型组脑梗死体积和神经行为评分显著增加(p p值)。结论:右美托咪定调节自噬和铁凋亡通路之间的串音,从而保护小鼠大脑免受缺血再灌注损伤,为未来缺血性脑卒中的治疗提供新的见解。
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
Neurological Research
Neurological Research 医学-临床神经学
CiteScore
3.60
自引率
0.00%
发文量
116
审稿时长
5.3 months
期刊介绍: Neurological Research is an international, peer-reviewed journal for reporting both basic and clinical research in the fields of neurosurgery, neurology, neuroengineering and neurosciences. It provides a medium for those who recognize the wider implications of their work and who wish to be informed of the relevant experience of others in related and more distant fields. The scope of the journal includes: •Stem cell applications •Molecular neuroscience •Neuropharmacology •Neuroradiology •Neurochemistry •Biomathematical models •Endovascular neurosurgery •Innovation in neurosurgery.
×
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:604180095
Book学术官方微信