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低频(1赫兹)重复经脊髓磁刺激可减轻脊髓损伤小鼠中NLRP3驱动的神经炎症并促进运动恢复。

Low-Frequency (1 Hz) Repetitive Trans-Spinal Magnetic Stimulation Attenuates NLRP3-Driven Neuroinflammation and Enhances Motor Recovery in Spinal Cord-Injured Mice.

作者信息

Song Haiwang, Yang Yuxi, Huang Lieyu, Li Yumei, Sun Baofei, Yu Zijiang, Zhang Mudan, Yang Dan

机构信息

Department of Human Anatomy, School of Basic Medicine, Guizhou Medical University, Gui'an New District, People's Republic of China.

Key Laboratory of Human Brain Bank for Functions and Diseases of Department of Education of Guizhou Province, College of Basic Medical, Guizhou Medical University, Gui'an New District, People's Republic of China.

出版信息

J Inflamm Res. 2025 Aug 18;18:11263-11284. doi: 10.2147/JIR.S516006. eCollection 2025.

DOI:10.2147/JIR.S516006
PMID:40873779
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12378149/
Abstract

PURPOSE

Investigate the effects of repetitive Trans-Spinal Magnetic Stimulation (rTSMS) on motor function recovery and the underlying mechanisms in mice after spinal cord injury.

METHODS

rTSMS was applied both in vivo and in vitro, Motor function was evaluated by the Basso Mouse Scale (BMS), grid walking errors, and Motor Evoked Potentials (MEPs). Cell viability, oxidative stress markers, and key proteins including AQP4, Bax, Bcl-2, cleaved caspase-3, inflammatory cytokines, and NLRP3 inflammasome components were analyzed. Retrograde tracing using rAAV/Retro and neuronal markers (NeuN, MAP2, β-III-tubulin) were analyzed by the Microplate Reader, Western Blot, ELISA, and Immunofluorescence (IF).

RESULTS

1 Hz rTSMS improved motor recovery, reduced lesion size, and enhanced MEPs compared to 20 Hz. It decreased spinal edema and oxidative stress, suppressed apoptosis, and inhibited NLRP3 inflammasome activation in microglia. GFAP was downregulated, while BDNF and anti-inflammatory cytokines (IL-4, IL-10) increased. Retrograde tracing showed enhanced survival of cortical motor neurons after 1 Hz rTSMS. In vitro, BV2 supernatants after MS reduced pro-inflammatory cytokines and promoted PC12 neuronal survival and maturation.

CONCLUSION

Specific frequency rTSMS at 1 Hz can inhibit NLRP3 inflammasome expression, reducing inflammation, promoting neuroprotection, and aiding hindlimb recovery after spinal cord injury in mice.

摘要

目的

研究重复经脊髓磁刺激(rTSMS)对脊髓损伤小鼠运动功能恢复的影响及其潜在机制。

方法

在体内和体外应用rTSMS,通过Basso小鼠量表(BMS)、网格行走误差和运动诱发电位(MEP)评估运动功能。分析细胞活力、氧化应激标志物以及包括水通道蛋白4(AQP4)、 Bax、Bcl-2、裂解的半胱天冬酶-3、炎性细胞因子和NLRP3炎性小体成分在内的关键蛋白。使用重组腺相关病毒/逆转录病毒(rAAV/Retro)进行逆行示踪,并通过酶标仪、蛋白质免疫印迹法、酶联免疫吸附测定法和免疫荧光法(IF)分析神经元标志物(NeuN、微管相关蛋白2(MAP2)、β-III微管蛋白)。

结果

与20 Hz相比,1 Hz的rTSMS改善了运动恢复,减小了损伤面积,并增强了MEP。它减轻了脊髓水肿和氧化应激,抑制了细胞凋亡,并抑制了小胶质细胞中NLRP3炎性小体的激活。胶质纤维酸性蛋白(GFAP)下调,而脑源性神经营养因子(BDNF)和抗炎细胞因子(白细胞介素-4(IL-4)、白细胞介素-10(IL-10))增加。逆行示踪显示,1 Hz rTSMS后皮质运动神经元的存活率提高。在体外,多发性硬化症(MS)后BV2细胞培养上清液减少了促炎细胞因子,并促进了PC12神经元的存活和成熟。

结论

1 Hz的特定频率rTSMS可抑制NLRP3炎性小体表达,减轻炎症,促进神经保护,并有助于小鼠脊髓损伤后后肢功能的恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a71/12378149/935fb2c53944/JIR-18-11263-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a71/12378149/1d13ed0457a5/JIR-18-11263-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a71/12378149/c29d167619f5/JIR-18-11263-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a71/12378149/25b08fb59b89/JIR-18-11263-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a71/12378149/6aa9c9b7b9e4/JIR-18-11263-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a71/12378149/935fb2c53944/JIR-18-11263-g0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a71/12378149/1d13ed0457a5/JIR-18-11263-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a71/12378149/c29d167619f5/JIR-18-11263-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a71/12378149/25b08fb59b89/JIR-18-11263-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a71/12378149/6aa9c9b7b9e4/JIR-18-11263-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3a71/12378149/935fb2c53944/JIR-18-11263-g0008.jpg

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本文引用的文献

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A Visual and Narrative Timeline Review of Spinal Cord Stimulation Technology and US Food and Drug Administration Milestones.脊髓刺激技术和美国食品药品监督管理局里程碑的可视化和叙事时间轴回顾。
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Repeated trans-spinal magnetic stimulation promotes microglial phagocytosis of myelin debris after spinal cord injury through LRP-1.
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rTMS reduces delta and increases theta oscillations in Alzheimer's disease: A visual-evoked and event-related potentials study.rTMS 降低阿尔茨海默病中的 δ 波并增加 θ 波振荡:一项视觉诱发电位和事件相关电位研究。
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