Transcranial magnetic stimulation through attenuating blood-spinal cord barrier disruption and reducing inflammatory response to improve motor function in rats with spinal cord injury

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-05-13 DOI:10.1016/j.brainresbull.2025.111385

Qingqin Xu , Zhongfu Zhang , Yuqing Zhai , Ji Chen , Jianhua Xu , Hemu Chen , Jianwei Lu

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引用次数: 0

Abstract

Background

Previous therapies for spinal cord injury (SCI) typically focus on the lesion site, neglecting the interconnected brain areas. Transcranial magnetic stimulation (TMS) is an emerging non-invasive neuromodulation technique, demonstrating potential in modulating the primary motor cortex to enhance SCI recovery.

Methods

The modified Allen's method was used to establish an SCI rat model. High-frequency repetitive TMS (HF-rTMS) intervention was initiated on the second day after modeling and continued for 56 days. Bioinformatics analysis identified key genes involved in the SCI pathological process, including MMP9, IL-1β, and IL-18. This study explored the functions and mechanisms of these genes in HF-rTMS-mediated motor recovery in SCI rats.

Results

Western blotting reveals that HF-rTMS decreases active-MMP9/pro-MMP9, TNF-α, IL-1β, and IL-18 proteins' expression, while increases β-DG, Occludin, Claudin-5, and ZO-1 proteins' expression in injured spinal cord (P < 0.001). Immunoﬂuorescence staining further shows that HF-rTMS reduces MMP9 positive cells, while enhances Occludin, Claudin-5, and ZO-1 positive cells (P < 0.001). Evans Blue staining indicates that HF-rTMS reduces blood-spinal cord barrier (BSCB) permeability following injury, while ELISA results demonstrate that HF-rTMS attenuates serum levels of pro-inflammatory cytokines. Motor-evoked potentials (MEP) assessment, HE staining, and BBB score show that HF-rTMS shortens MEP latency, enhances MEP amplitude, reduces spinal cord damage and improves motor function (P < 0.001).

Conclusion

These findings reveal that HF-rTMS may be associated with suppressing MMP9 activation, protecting tight junction proteins, diminishing basement membrane destruction, and maintaining BSCB integrity. Simultaneously, it may alleviate pro-inflammatory cytokine-induced inflammation, thereby reducing spinal cord tissue damage and promoting motor recovery after SCI.

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经颅磁刺激通过减弱血脊髓屏障破坏和减少炎症反应改善脊髓损伤大鼠的运动功能

以往的脊髓损伤治疗通常集中在损伤部位，而忽视了相互联系的大脑区域。经颅磁刺激（TMS）是一种新兴的非侵入性神经调节技术，显示出调节初级运动皮层以增强脊髓损伤恢复的潜力。方法采用改良Allen法建立脊髓损伤大鼠模型。高频重复经颅磁刺激（HF-rTMS）干预于造模后第2天开始，持续56天。生物信息学分析确定了参与脊髓损伤病理过程的关键基因，包括MMP9、IL-1β和IL-18。本研究探讨了这些基因在hf - rtms介导的脊髓损伤大鼠运动恢复中的功能和机制。结果western blotting结果显示，HF-rTMS降低损伤脊髓中活性mmp9 /pro mmp9、TNF-α、IL-1β和IL-18蛋白的表达，增加β-DG、Occludin、Claudin-5和ZO-1蛋白的表达（P <； 0.001）。免疫荧光染色进一步显示，HF-rTMS降低了MMP9阳性细胞，而增强了Occludin、Claudin-5和ZO-1阳性细胞（P <； 0.001）。Evans Blue染色显示HF-rTMS降低损伤后血脊髓屏障（BSCB）的通透性，而ELISA结果显示HF-rTMS降低了血清中促炎细胞因子的水平。运动诱发电位（MEP）评估、HE染色和BBB评分显示，HF-rTMS缩短MEP潜伏期，增强MEP振幅，减轻脊髓损伤，改善运动功能（P <； 0.001）。结论HF-rTMS可能具有抑制MMP9活化、保护紧密连接蛋白、减少基底膜破坏、维持BSCB完整性等作用。同时，它可以减轻促炎细胞因子引起的炎症，从而减轻脊髓组织损伤，促进脊髓损伤后的运动恢复。

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

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.