Electroacupuncture improves ischemic stroke by intervening in neurovascular remodeling via miR-210-mediated regulation of the Wnt/HIF1A/netrin-1 signaling axis.

IF 1.6 4区医学 Q4 NEUROSCIENCES

Neuroreport Pub Date : 2025-06-26 DOI:10.1097/WNR.0000000000002181

Chao Liang, Kebing Zheng, Jiao Liu, Shaoping Chen, Mengrui Zhang, Chong Sun, Qinghua Wu

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引用次数: 0

Abstract

Objective: Cerebral infarction (stroke) is a major global public health issue. This study explores the mechanisms by which electroacupuncture affects motor function after cerebral infarction by combining complementary experimental approaches in middle cerebral artery occlusion mice. The work focuses particularly on the Wnt/hypoxia-inducible factor-1 alpha (HIF1A)/netrin-1 signaling axis and downstream targets, including netrin-1 and vascular endothelial growth factor (VEGF), to provide a comprehensive understanding of the mechanisms that underpin electroacupuncture stimulation after stroke.

Methods: The middle cerebral artery occlusion model was established with electroacupuncture intervention. The cerebral cortex of mice was collected for detections, including RNA sequencing, western blot, immunofluorescence, quantitative PCR, and so forth. HIF1A-overexpressing and knockdown cell lines in SH-SY5Y cells were used for further verification.

Results: Exosome and RNA sequencing identified the key microRNA mir-210 and the Wnt/HIF1A/netrin-1 signaling axis after electroacupuncture treatment at head acupoints in the murine model. In addition, the HIF1A transcription factor was upregulated and bound to promoters of genes for netrin-1 and VEGF thereby activating transcription of these loci. Dual luciferase reporter assays revealed that mir-210 targets the gene for the tumor suppressor adenomatous polyposis coli, thereby stimulating the Wnt-signaling pathway. Furthermore, behavioral experiments demonstrated that electroacupuncture intervention in the Wnt/HIF1A/netrin-1 signaling axis improved motor function in middle cerebral artery occlusion mice.

Conclusion: The study reveals that electroacupuncture stimulation promotes angiogenesis and neural reconstruction after cerebral infarction by regulating the Wnt/HIF1A/netrin-1 signaling axis through mir-210, and suggests novel therapeutic targets for the treatment of cerebral infarction with electroacupuncture.

查看原文本刊更多论文

电针通过mir -210介导的Wnt/HIF1A/netrin-1信号轴调控干预神经血管重构，改善缺血性卒中。

目的：脑梗死（脑卒中）是一个重大的全球公共卫生问题。本研究采用互补实验方法，探讨电针对大脑中动脉闭塞小鼠脑梗死后运动功能的影响机制。这项工作特别关注Wnt/缺氧诱导因子-1 α (HIF1A)/netrin-1信号轴和下游靶点，包括netrin-1和血管内皮生长因子（VEGF），以全面了解脑卒中后电针刺激的机制。方法：采用电针干预建立大鼠大脑中动脉闭塞模型。采集小鼠大脑皮层进行检测，包括RNA测序、western blot、免疫荧光、定量PCR等。SH-SY5Y细胞中hif1a过表达和敲低细胞系进一步验证。结果：外泌体和RNA测序鉴定了小鼠模型头部穴位电针治疗后的关键microRNA mir-210和Wnt/HIF1A/netrin-1信号轴。此外，HIF1A转录因子被上调并结合到netrin-1和VEGF基因的启动子上，从而激活这些位点的转录。双荧光素酶报告基因检测显示，mir-210靶向抑制肿瘤的大肠腺瘤性息肉病基因，从而刺激wnt信号通路。此外，行为学实验表明，电针干预Wnt/HIF1A/netrin-1信号轴可改善大脑中动脉闭塞小鼠的运动功能。结论：本研究揭示电针刺激可通过mir-210调节Wnt/HIF1A/netrin-1信号轴，促进脑梗死后血管生成和神经重建，为电针治疗脑梗死提供新的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroreport 医学-神经科学

CiteScore

3.20

自引率

0.00%

发文量

150

审稿时长

1 months

期刊介绍： NeuroReport is a channel for rapid communication of new findings in neuroscience. It is a forum for the publication of short but complete reports of important studies that require very fast publication. Papers are accepted on the basis of the novelty of their finding, on their significance for neuroscience and on a clear need for rapid publication. Preliminary communications are not suitable for the Journal. Submitted articles undergo a preliminary review by the editor. Some articles may be returned to authors without further consideration. Those being considered for publication will undergo further assessment and peer-review by the editors and those invited to do so from a reviewer pool. The core interest of the Journal is on studies that cast light on how the brain (and the whole of the nervous system) works. We aim to give authors a decision on their submission within 2-5 weeks, and all accepted articles appear in the next issue to press.