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

作者：Qingqin Xu, Z.-C. Zhang, Yuqing Zhai, Jihua Chen, Jianhua Xu, Hemu Chen, Jianwei Lü · 发表于：Brain Research Bulletin · 年份：2025 · DOI：10.1016/j.brainresbull.2025.111385 · 被引用次数：9 · 研究领域：Spinal Cord Injury Research、Transcranial Magnetic Stimulation Studies、Nerve injury and regeneration

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, red...