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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| Format: | Article |
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Elsevier
2025-06-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025001972 |
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| author | Qingqin Xu Zhongfu Zhang Yuqing Zhai Ji Chen Jianhua Xu Hemu Chen Jianwei Lu |
| author_facet | Qingqin Xu Zhongfu Zhang Yuqing Zhai Ji Chen Jianhua Xu Hemu Chen Jianwei Lu |
| author_sort | Qingqin Xu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-29cc41abc41e4034922659c928b7c4e7 |
| institution | DOAJ |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-29cc41abc41e4034922659c928b7c4e72025-08-20T03:13:39ZengElsevierBrain Research Bulletin1873-27472025-06-0122611138510.1016/j.brainresbull.2025.111385Transcranial magnetic stimulation through attenuating blood-spinal cord barrier disruption and reducing inflammatory response to improve motor function in rats with spinal cord injuryQingqin Xu0Zhongfu Zhang1Yuqing Zhai2Ji Chen3Jianhua Xu4Hemu Chen5Jianwei Lu6College of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 200000, China; Engineering Research Center for Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai 200000, China; Department of Rehabilitation Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, ChinaCollege of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 200000, China; Engineering Research Center for Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai 200000, ChinaCollege of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 200000, China; Engineering Research Center for Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai 200000, ChinaDepartment of Rehabilitation Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, ChinaDepartment of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China; Corresponding authors.Department of Rehabilitation Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China; Corresponding authors.College of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 200000, China; Engineering Research Center for Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai 200000, China; Corresponding author at: College of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai 200000, China.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.http://www.sciencedirect.com/science/article/pii/S0361923025001972Blood-spinal cord barrierSpinal cord injuryInflammatory responseMotor functionTranscranial magnetic stimulation |
| spellingShingle | Qingqin Xu Zhongfu Zhang Yuqing Zhai Ji Chen Jianhua Xu Hemu Chen Jianwei Lu Transcranial magnetic stimulation through attenuating blood-spinal cord barrier disruption and reducing inflammatory response to improve motor function in rats with spinal cord injury Brain Research Bulletin Blood-spinal cord barrier Spinal cord injury Inflammatory response Motor function Transcranial magnetic stimulation |
| title | Transcranial magnetic stimulation through attenuating blood-spinal cord barrier disruption and reducing inflammatory response to improve motor function in rats with spinal cord injury |
| title_full | Transcranial magnetic stimulation through attenuating blood-spinal cord barrier disruption and reducing inflammatory response to improve motor function in rats with spinal cord injury |
| title_fullStr | Transcranial magnetic stimulation through attenuating blood-spinal cord barrier disruption and reducing inflammatory response to improve motor function in rats with spinal cord injury |
| title_full_unstemmed | Transcranial magnetic stimulation through attenuating blood-spinal cord barrier disruption and reducing inflammatory response to improve motor function in rats with spinal cord injury |
| title_short | Transcranial magnetic stimulation through attenuating blood-spinal cord barrier disruption and reducing inflammatory response to improve motor function in rats with spinal cord injury |
| title_sort | transcranial magnetic stimulation through attenuating blood spinal cord barrier disruption and reducing inflammatory response to improve motor function in rats with spinal cord injury |
| topic | Blood-spinal cord barrier Spinal cord injury Inflammatory response Motor function Transcranial magnetic stimulation |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025001972 |
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