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

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...

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Main Authors: Qingqin Xu, Zhongfu Zhang, Yuqing Zhai, Ji Chen, Jianhua Xu, Hemu Chen, Jianwei Lu
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923025001972
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Summary: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.
ISSN:1873-2747