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体重支持的跑步机训练通过在亚急性期降低星形胶质细胞的反应性,减少脊髓损伤大鼠的胶质瘢痕过度生长。

Body weight-supported treadmill training reduces glial scar overgrowth in SCI rats by decreasing the reactivity of astrocytes during the subacute phase.

作者信息

Cai Jili, Wang Yu, Zhai Chenyuan, Jiang Kunmao, Wang Zun, Fang Lu, Li Xiangzhe, Zhu Chenchen, Liu Wentao, Wang Tong, Wu Qi

机构信息

Rehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Department of Rehabilitation, Suzhou Hospital, Nanjing Medical University, Suzhou, 215008, China.

出版信息

BMC Neurosci. 2025 Apr 28;26(1):30. doi: 10.1186/s12868-025-00947-7.

DOI:10.1186/s12868-025-00947-7
PMID:40295901
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12039159/
Abstract

BACKGROUND

Spinal cord injury is followed by glial scar formation, which was long seen mainly as a physical barrier preventing axonal regeneration. Glial scar astrocytes lead to glial scar formation and produce inhibitory factors to prevent axons from growing through the scar, while inhibiting the conversion of reactive astrocytes into glial scar-forming astrocytes may represent an ideal treatment for CNS injury. Exercise is a non-invasive and effective therapeutic intervention for clinical rehabilitation of spinal cord injury. However, its precise therapeutic mechanisms still need to be continuously explored.

METHODS

30 rats were randomly assigned to three groups (Sham, SCI, SCI + BWSTT; n = 10 rats per group). In this study, we employed the BBB scales and gait analysis system to examine the behavioral functions of the rats in each group. Furthermore, we utilized immunoblotting of spinal cord tissue at the injury site, in addition to histological staining and immunofluorescence staining, to explore glial scar aggregation and axonal regeneration in each group of rats.

RESULTS

Our results revealed that hindlimb motor function was significantly improved in SCI rats after a sustained subacute period of BWSTT, accompanied by the promotion of histological repair and nerve regeneration. Subsequent immunofluorescence staining and immunoblotting showed diminished astrocyte reactivity in the region surrounding the spinal cord injury as well as reduced expression and distribution of collagen fibers near the lesion after BWSTT. Additionally, a significant decrease in the expression of MMP-2/9, which is closely related to astrocyte migration, was observed in the vicinity of spinal cord tissue lesions.

CONCLUSION

Our study demonstrates that a sustained BWSTT intervention during the subacute phase of spinal cord injury can effectively reduce astrocyte reactivity and glial scarring overgrowth, thereby facilitating functional recovery after SCI.

摘要

背景

脊髓损伤后会形成胶质瘢痕,长期以来,胶质瘢痕主要被视为阻止轴突再生的物理屏障。胶质瘢痕星形胶质细胞导致胶质瘢痕形成并产生抑制因子,以阻止轴突穿过瘢痕生长,而抑制反应性星形胶质细胞向形成胶质瘢痕的星形胶质细胞转化可能是治疗中枢神经系统损伤的理想方法。运动是脊髓损伤临床康复的一种非侵入性有效治疗干预措施。然而,其确切的治疗机制仍需不断探索。

方法

将30只大鼠随机分为三组(假手术组、脊髓损伤组、脊髓损伤+体重支持训练组;每组n = 10只大鼠)。在本研究中,我们采用BBB评分量表和步态分析系统来检测每组大鼠的行为功能。此外,除了组织学染色和免疫荧光染色外,我们还利用损伤部位脊髓组织的免疫印迹法,来探索每组大鼠的胶质瘢痕聚集和轴突再生情况。

结果

我们的结果显示,在持续亚急性期进行体重支持训练后,脊髓损伤大鼠的后肢运动功能显著改善,同时伴有组织学修复和神经再生的促进。随后的免疫荧光染色和免疫印迹显示,体重支持训练后,脊髓损伤周围区域的星形胶质细胞反应性降低,损伤附近的胶原纤维表达和分布减少。此外,在脊髓组织损伤附近观察到与星形胶质细胞迁移密切相关的MMP - 2/9表达显著降低。

结论

我们的研究表明,在脊髓损伤亚急性期进行持续的体重支持训练干预可以有效降低星形胶质细胞反应性和胶质瘢痕过度生长,从而促进脊髓损伤后的功能恢复。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e224/12039159/0df34168c86d/12868_2025_947_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e224/12039159/9bd1decfb1b0/12868_2025_947_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e224/12039159/0df34168c86d/12868_2025_947_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e224/12039159/9bd1decfb1b0/12868_2025_947_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e224/12039159/6662a304f0b4/12868_2025_947_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e224/12039159/0fe1d1ed30ab/12868_2025_947_Fig4_HTML.jpg
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本文引用的文献

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Molecular Pathway Changes Associated with Different Post-Conditioning Exercise Interventions After Experimental TBI.实验性创伤性脑损伤后不同后适应运动干预相关的分子通路变化
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创伤性脑损伤中的星形胶质细胞、反应性星形胶质增生和胶质瘢痕形成。
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Treadmill training improves neural function recovery in rats with spinal cord injury via JAK2/STAT3 signaling pathway and attenuating apoptosis. treadmill 训练通过 JAK2/STAT3 信号通路和减轻细胞凋亡改善脊髓损伤大鼠的神经功能恢复。
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Enhancement of motor functional recovery in thoracic spinal cord injury: voluntary wheel running versus forced treadmill exercise.胸段脊髓损伤后运动功能恢复的增强:自主轮跑与强制跑步机运动对比
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