• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

Toll 样受体 7 预处理通过新型 I 型干扰素介导的机制诱导强烈的神经保护作用抵抗中风。

Toll-like receptor 7 preconditioning induces robust neuroprotection against stroke by a novel type I interferon-mediated mechanism.

机构信息

Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, OR 97239, USA.

出版信息

Stroke. 2012 May;43(5):1383-9. doi: 10.1161/STROKEAHA.111.641522. Epub 2012 Mar 8.

DOI:10.1161/STROKEAHA.111.641522
PMID:22403050
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3943206/
Abstract

BACKGROUND AND PURPOSE

Systemic administration of Toll-like receptor (TLR) 4 and TLR9 agonists before cerebral ischemia have been shown to reduce ischemic injury by reprogramming the response of the brain to stroke. Our goal was to explore the mechanism of TLR-induced neuroprotection by determining whether a TLR7 agonist also protects against stroke injury.

METHODS

C57Bl/6, TNF(-/-), interferon (IFN) regulatory factor 7(-/-), or type I IFN receptor (IFNAR)(-/-) mice were subcutaneously administered the TLR7 agonist Gardiquimod (GDQ) 72 hours before middle cerebral artery occlusion. Infarct volume and functional outcome were determined after reperfusion. Plasma cytokine responses and induction of mRNA for IFN-related genes in the brain were measured. IFNAR(-/-) mice also were treated with the TLR4 agonist (lipopolysaccharide) or the TLR9 agonist before middle cerebral artery occlusion and infarct volumes measured.

RESULTS

The results show that GDQ reduces infarct volume as well as functional deficits in mice. GDQ pretreatment provided robust neuroprotection in TNF(-/-) mice, indicating that TNF was not essential. GDQ induced a significant increase in plasma IFNα levels and both IRF7(-/-) and IFNAR(-/-) mice failed to be protected, implicating a role for IFN signaling in TLR7-mediated protection.

CONCLUSIONS

Our studies provide the first evidence that TLR7 preconditioning can mediate neuroprotection against ischemic injury. Moreover, we show that the mechanism of protection is unique from other TLR preconditioning ligands in that it is independent of TNF and dependent on IFNAR.

摘要

背景与目的

在脑缺血前全身性给予 Toll 样受体（TLR）4 和 TLR9 激动剂已被证明通过重新编程大脑对中风的反应来减少缺血性损伤。我们的目标是通过确定 TLR7 激动剂是否也能保护免受中风损伤来探索 TLR 诱导的神经保护机制。

方法

C57Bl/6、TNF（-/-）、干扰素（IFN）调节因子 7（-/-）或 I 型 IFN 受体（IFNAR）（-/-）小鼠在大脑中动脉闭塞前 72 小时皮下给予 TLR7 激动剂 Gardiquimod（GDQ）。再灌注后确定梗死体积和功能结果。测量血浆细胞因子反应和脑中 IFN 相关基因的 mRNA 诱导。IFNAR（-/-）小鼠也在大脑中动脉闭塞前用 TLR4 激动剂（脂多糖）或 TLR9 激动剂治疗，并测量梗死体积。

结果

结果表明，GDQ 可减少小鼠的梗死体积和功能缺陷。GDQ 预处理为 TNF（-/-）小鼠提供了强大的神经保护作用，表明 TNF 不是必需的。GDQ 诱导血浆 IFNα 水平显著增加，IRF7（-/-）和 IFNAR（-/-）小鼠均未得到保护，表明 IFN 信号转导在 TLR7 介导的保护中起作用。

结论

我们的研究首次提供了证据，表明 TLR7 预处理可以介导对缺血性损伤的神经保护。此外，我们表明，保护机制与其他 TLR 预处理配体不同，它独立于 TNF 并依赖于 IFNAR。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d57/3943206/2701e8d37161/nihms550621f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d57/3943206/7365ca4b0067/nihms550621f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d57/3943206/5a5c47a67cc6/nihms550621f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d57/3943206/e45d4a4de61b/nihms550621f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d57/3943206/c0b84bd2c34d/nihms550621f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d57/3943206/2701e8d37161/nihms550621f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d57/3943206/7365ca4b0067/nihms550621f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d57/3943206/5a5c47a67cc6/nihms550621f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d57/3943206/e45d4a4de61b/nihms550621f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d57/3943206/c0b84bd2c34d/nihms550621f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d57/3943206/2701e8d37161/nihms550621f5.jpg

相似文献

1
Toll-like receptor 7 preconditioning induces robust neuroprotection against stroke by a novel type I interferon-mediated mechanism.Toll 样受体 7 预处理通过新型 I 型干扰素介导的机制诱导强烈的神经保护作用抵抗中风。
Stroke. 2012 May;43(5):1383-9. doi: 10.1161/STROKEAHA.111.641522. Epub 2012 Mar 8.
2
Cytosolic Receptor Melanoma Differentiation-Associated Protein 5 Mediates Preconditioning-Induced Neuroprotection Against Cerebral Ischemic Injury.胞质受体黑色素瘤分化相关蛋白5介导预处理诱导的对脑缺血损伤的神经保护作用。
Stroke. 2016 Jan;47(1):262-6. doi: 10.1161/STROKEAHA.115.010329. Epub 2015 Nov 12.
3
Toll-like receptor 9: a new target of ischemic preconditioning in the brain.Toll样受体9：脑缺血预处理的新靶点。
J Cereb Blood Flow Metab. 2008 May;28(5):1040-7. doi: 10.1038/sj.jcbfm.9600606. Epub 2008 Jan 9.
4
Poly-ICLC preconditioning protects the blood-brain barrier against ischemic injury in vitro through type I interferon signaling.聚肌胞预处理通过 I 型干扰素信号通路保护血脑屏障免受体外缺血性损伤。
J Neurochem. 2012 Nov;123 Suppl 2(Suppl 2):75-85. doi: 10.1111/j.1471-4159.2012.07946.x.
5
Effects of delayed intraventricular TLR7 agonist administration on long-term neurological outcome following asphyxia in the preterm fetal sheep.延迟脑室 TLR7 激动剂给药对早产胎羊窒息后长期神经结局的影响。
Sci Rep. 2020 Apr 23;10(1):6904. doi: 10.1038/s41598-020-63770-6.
6
Toll-like receptor 4, Toll-like receptor 7 and Toll-like receptor 9 agonists enhance immune responses against blood-stage Plasmodium chabaudi infection in BALB/c mice.Toll 样受体 4、Toll 样受体 7 和 Toll 样受体 9 激动剂增强 BALB/c 小鼠血期疟原虫感染的免疫应答。
Int Immunopharmacol. 2020 Dec;89(Pt B):107096. doi: 10.1016/j.intimp.2020.107096. Epub 2020 Oct 19.
7
LPS preconditioning redirects TLR signaling following stroke: TRIF-IRF3 plays a seminal role in mediating tolerance to ischemic injury.脂多糖预处理可重定向卒中后的 TLR 信号：TRIF-IRF3 在介导对缺血性损伤的耐受中起主要作用。
J Neuroinflammation. 2011 Oct 14;8:140. doi: 10.1186/1742-2094-8-140.
8
Plasmacytoid dendritic cell-derived type I interferon is crucial for the adjuvant activity of Toll-like receptor 7 agonists.浆细胞样树突状细胞衍生的 I 型干扰素对于 Toll 样受体 7 激动剂的佐剂活性至关重要。
Blood. 2010 Mar 11;115(10):1949-57. doi: 10.1182/blood-2009-08-238543. Epub 2010 Jan 11.
9
The early induction of suppressor of cytokine signaling 1 and the downregulation of toll-like receptors 7 and 9 induce tolerance in costimulated macrophages.细胞因子信号转导抑制因子1的早期诱导以及Toll样受体7和9的下调可诱导共刺激巨噬细胞产生耐受性。
Mol Cells. 2015 Jan 31;38(1):26-32. doi: 10.14348/molcells.2015.2136. Epub 2014 Dec 15.
10
Toll-like receptor 4 is involved in neuroprotection afforded by ischemic preconditioning.Toll样受体4参与缺血预处理所提供的神经保护作用。
J Neurochem. 2009 Apr;109(1):287-94. doi: 10.1111/j.1471-4159.2009.05972.x. Epub 2009 Feb 7.

引用本文的文献

1
Profiling X chromosome genes expression relevant to sex dimorphism in stroke: insights from transcriptomics landscape analysis.分析与中风性别差异相关的X染色体基因表达：转录组学景观分析的见解
Front Genet. 2025 Mar 21;16:1479270. doi: 10.3389/fgene.2025.1479270. eCollection 2025.
2
The role of immunity in insulin resistance in patients with polycystic ovary syndrome.免疫在多囊卵巢综合征患者胰岛素抵抗中的作用。
Front Endocrinol (Lausanne). 2025 Jan 22;15:1464561. doi: 10.3389/fendo.2024.1464561. eCollection 2024.
3
drives sex differences in age- and Alzheimer's disease-related demyelination.

本文引用的文献

1
LPS preconditioning redirects TLR signaling following stroke: TRIF-IRF3 plays a seminal role in mediating tolerance to ischemic injury.脂多糖预处理可重定向卒中后的 TLR 信号：TRIF-IRF3 在介导对缺血性损伤的耐受中起主要作用。
J Neuroinflammation. 2011 Oct 14;8:140. doi: 10.1186/1742-2094-8-140.
2
Multiple preconditioning paradigms converge on interferon regulatory factor-dependent signaling to promote tolerance to ischemic brain injury.多种预处理方案集中于干扰素调节因子依赖性信号传导，以促进对缺血性脑损伤的耐受。
J Neurosci. 2011 Jun 8;31(23):8456-63. doi: 10.1523/JNEUROSCI.0821-11.2011.
3
Toll-like receptors 2 and 4 in ischemic stroke: outcome and therapeutic values.
导致与年龄和阿尔茨海默病相关的脱髓鞘作用存在性别差异。
Science. 2024 Nov 29;386(6725):eadk7844. doi: 10.1126/science.adk7844.
4
Impact of inflammatory preconditioning on murine microglial proteome response induced by focal ischemic brain injury.炎症预处理对局灶性缺血性脑损伤诱导的小鼠小胶质细胞蛋白质组反应的影响。
Front Immunol. 2024 Apr 9;15:1227355. doi: 10.3389/fimmu.2024.1227355. eCollection 2024.
5
Cortex-specific transcriptome profiling reveals upregulation of interferon-regulated genes after deeper cerebral hypoperfusion in mice.皮质特异性转录组分析揭示小鼠深度脑灌注不足后干扰素调节基因上调。
Front Physiol. 2023 Mar 13;14:1056354. doi: 10.3389/fphys.2023.1056354. eCollection 2023.
6
Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions.涉及缺血性脑卒中的信号通路：分子机制和治疗干预。
Signal Transduct Target Ther. 2022 Jul 6;7(1):215. doi: 10.1038/s41392-022-01064-1.
7
A STING agonist preconditions against ischaemic stroke via an adaptive antiviral Type 1 interferon response.一种STING激动剂通过适应性抗病毒1型干扰素反应对缺血性中风起到预处理作用。
Brain Commun. 2022 May 24;4(3):fcac133. doi: 10.1093/braincomms/fcac133. eCollection 2022.
8
Molecular Basis for the Activation of Human Innate Immune Response by the Flagellin Derived from Plant-Pathogenic Bacterium, .植物病原菌鞭毛蛋白激活人天然免疫反应的分子基础。
Int J Mol Sci. 2021 Jun 28;22(13):6920. doi: 10.3390/ijms22136920.
9
Toll-Like Receptor Signaling Pathways: Novel Therapeutic Targets for Cerebrovascular Disorders. Toll 样受体信号通路：脑血管疾病的新治疗靶点。
Int J Mol Sci. 2021 Jun 7;22(11):6153. doi: 10.3390/ijms22116153.
10
A murine model of Lyme disease demonstrates that Borrelia burgdorferi colonizes the dura mater and induces inflammation in the central nervous system.莱姆病的小鼠模型表明，伯氏疏螺旋体定殖于硬脑膜并在中枢神经系统中引发炎症。
PLoS Pathog. 2021 Feb 1;17(2):e1009256. doi: 10.1371/journal.ppat.1009256. eCollection 2021 Feb.
缺血性脑卒中中 Toll 样受体 2 和 4：预后和治疗价值。
J Cereb Blood Flow Metab. 2011 Jun;31(6):1424-31. doi: 10.1038/jcbfm.2010.231. Epub 2011 Jan 5.
4
Systemic lipopolysaccharide protects the brain from ischemic injury by reprogramming the response of the brain to stroke: a critical role for IRF3.全身脂多糖通过重新编程大脑对中风的反应来保护大脑免受缺血性损伤：IRF3的关键作用。
J Neurosci. 2009 Aug 5;29(31):9839-49. doi: 10.1523/JNEUROSCI.2496-09.2009.
5
Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant.树突状细胞需要全身性I型干扰素反应来成熟，并以聚肌胞苷酸作为佐剂诱导CD4+ Th1免疫。
J Exp Med. 2009 Jul 6;206(7):1589-602. doi: 10.1084/jem.20090247. Epub 2009 Jun 29.
6
NF-kappaB signaling in cerebral ischemia.脑缺血中的核因子-κB信号传导
Neuroscience. 2009 Feb 6;158(3):995-1006. doi: 10.1016/j.neuroscience.2008.07.007. Epub 2008 Jul 10.
7
Preconditioning with a TLR2 specific ligand increases resistance to cerebral ischemia/reperfusion injury.用TLR2特异性配体进行预处理可增加对脑缺血/再灌注损伤的抵抗力。
J Neuroimmunol. 2008 Aug 13;199(1-2):75-82. doi: 10.1016/j.jneuroim.2008.05.009. Epub 2008 Jun 27.
8
Toll-like receptor 4 is involved in subacute stress-induced neuroinflammation and in the worsening of experimental stroke.Toll样受体4参与亚急性应激诱导的神经炎症反应以及实验性中风病情的恶化。
Stroke. 2008 Apr;39(4):1314-20. doi: 10.1161/STROKEAHA.107.498212. Epub 2008 Feb 28.
9
Toll-like receptor 9: a new target of ischemic preconditioning in the brain.Toll样受体9：脑缺血预处理的新靶点。
J Cereb Blood Flow Metab. 2008 May;28(5):1040-7. doi: 10.1038/sj.jcbfm.9600606. Epub 2008 Jan 9.
10
Toll-like receptor 2 mediates CNS injury in focal cerebral ischemia.Toll样受体2介导局灶性脑缺血中的中枢神经系统损伤。
J Neuroimmunol. 2007 Oct;190(1-2):28-33. doi: 10.1016/j.jneuroim.2007.07.023. Epub 2007 Sep 12.