运动疗法通过调节PKA/CREB信号通路促进大鼠脊髓损伤后神经重构和功能恢复

IF 6.3 1区医学 Q1 DERMATOLOGY

Burns & Trauma Pub Date : 2025-01-22 DOI:10.1093/burnst/tkae058

Xinwang Ying, Qingfeng Xie, Yanfang Zhao, Jiamen Shen, Junqing Huang, Zhiyi Feng, Liuxi Chu, Junpeng Xu, Dawei Jiang, Ping Wu, Yanming Zuo, Shengcun Li, Chang Jiang, Xiaokun Li, Zhouguang Wang

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引用次数: 0

摘要

脊髓损伤（SCI）后神经元结构被破坏，导致功能损伤。运动疗法（ET）在脊髓损伤后神经重构临床治疗中的有效性及其潜在机制尚不清楚。本研究旨在探讨ET对脊髓损伤大鼠神经重塑的影响及相关机制。方法将大鼠随机分为假手术组、假手术+ ET、单独SCI、SCI + H89、SCI + ET、SCI + ET + H89。采用运动诱发电位（MEP）、视频捕获和分析、basso - beatty - bresnahan （BBB）评分、western blotting、透射电镜、苏木精和伊红染色、尼索尔染色、甘氨酸银染色、免疫荧光和高尔基染色等技术评估信号传导能力、神经功能缺损、后肢性能、蛋白质表达水平、神经元超微结构和组织形态。h89是一种靶向蛋白激酶A (PKA)/cAMP反应元件结合（CREB）信号通路的抑制剂，用于研究其分子机制。结果本研究发现，ET可减轻脊髓损伤大鼠神经元损伤，保护残组织，促进运动神经元、神经丝、树突/轴突、突触和髓鞘的重塑，重组神经回路，促进运动功能恢复。从机制上看，ET主要通过介导神经元PKA/CREB信号通路起作用。结论：(1)ET可抵消h89诱导的脊髓损伤后PKA/CREB信号通路的抑制；(2) ET可显著减轻神经元损伤，改善运动功能障碍；(3) ET通过介导PKA/CREB信号通路促进神经元再生；(4) ET通过PKA/CREB信号通路增强脊髓损伤后突触和树突脊柱可塑性以及髓鞘重塑。

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Exercise therapy facilitates neural remodeling and functional recovery post-spinal cord injury via PKA/CREB signaling pathway modulation in rats

Background Neuronal structure is disrupted after spinal cord injury (SCI), causing functional impairment. The effectiveness of exercise therapy (ET) in clinical settings for nerve remodeling post-SCI and its underlying mechanisms remain unclear. This study aims to explore the effects and related mechanisms of ET on nerve remodeling in SCI rats. Methods We randomly assigned rats to various groups: sham-operated group, sham-operated + ET, SCI alone, SCI + H89, SCI + ET, and SCI + ET + H89. Techniques including motor-evoked potential (MEP), video capture and analysis, the Basso–Beattie–Bresnahan (BBB) scale, western blotting, transmission electron microscopy, hematoxylin and eosin staining, Nissl staining, glycine silver staining, immunofluorescence, and Golgi staining were utilized to assess signal conduction capabilities, neurological deficits, hindlimb performance, protein expression levels, neuron ultrastructure, and tissue morphology. H89—an inhibitor that targets the protein kinase A (PKA)/cAMP response element-binding (CREB) signaling pathway—was employed to investigate molecular mechanisms. Results This study found that ET can reduce neuronal damage in rats with SCI, protect residual tissue, promote the remodeling of motor neurons, neurofilaments, dendrites/axons, synapses, and myelin sheaths, reorganize neural circuits, and promote motor function recovery. In terms of mechanism, ET mainly works by mediating the PKA/CREB signaling pathway in neurons. Conclusions Our findings indicated that: (1) ET counteracted the H89-induced suppression of the PKA/CREB signaling pathway following SCI; (2) ET significantly alleviated neuronal injury and improved motor dysfunction; (3) ET facilitated neuronal regeneration by mediating the PKA/CREB signaling pathway; (4) ET enhanced synaptic and dendritic spine plasticity, as well as myelin sheath remodeling, post-SCI through the PKA/CREB signaling pathway.

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来源期刊

Burns & Trauma 医学-皮肤病学

CiteScore

8.40

自引率

9.40%

发文量

186

审稿时长

6 weeks

期刊介绍： The first open access journal in the field of burns and trauma injury in the Asia-Pacific region, Burns & Trauma publishes the latest developments in basic, clinical and translational research in the field. With a special focus on prevention, clinical treatment and basic research, the journal welcomes submissions in various aspects of biomaterials, tissue engineering, stem cells, critical care, immunobiology, skin transplantation, and the prevention and regeneration of burns and trauma injuries. With an expert Editorial Board and a team of dedicated scientific editors, the journal enjoys a large readership and is supported by Southwest Hospital, which covers authors'' article processing charges.