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

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 inhibit...

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Main Authors: Jili Cai, Yu Wang, Chenyuan Zhai, Kunmao Jiang, Zun Wang, Lu Fang, Xiangzhe Li, Chenchen Zhu, Wentao Liu, Tong Wang, Qi Wu
Format: Article
Language:English
Published: BMC 2025-04-01
Series:BMC Neuroscience
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Online Access:https://doi.org/10.1186/s12868-025-00947-7
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author Jili Cai
Yu Wang
Chenyuan Zhai
Kunmao Jiang
Zun Wang
Lu Fang
Xiangzhe Li
Chenchen Zhu
Wentao Liu
Tong Wang
Qi Wu
author_facet Jili Cai
Yu Wang
Chenyuan Zhai
Kunmao Jiang
Zun Wang
Lu Fang
Xiangzhe Li
Chenchen Zhu
Wentao Liu
Tong Wang
Qi Wu
author_sort Jili Cai
collection DOAJ
description 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.
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spelling doaj-art-bf0add7a6a4b4d038258a53939a8a48d2025-08-20T02:55:31ZengBMCBMC Neuroscience1471-22022025-04-0126111210.1186/s12868-025-00947-7Body weight-supported treadmill training reduces glial scar overgrowth in SCI rats by decreasing the reactivity of astrocytes during the subacute phaseJili Cai0Yu Wang1Chenyuan Zhai2Kunmao Jiang3Zun Wang4Lu Fang5Xiangzhe Li6Chenchen Zhu7Wentao Liu8Tong Wang9Qi Wu10Rehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical UniversityRehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Rehabilitation, Suzhou Hospital, Nanjing Medical UniversityJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical UniversityRehabilitation Medicine Department, School of Acupuncture and Tuina, School of Health and Rehabilitation, Nanjing University of Chinese MedicineRehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical UniversityRehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical UniversityRehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical UniversityRehabilitation Medicine Center, The First Affiliated Hospital of Nanjing Medical UniversityDepartment of Rehabilitation, Hengyang Medical School, The First Affiliated Hospital, University of South ChinaAbstract 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.https://doi.org/10.1186/s12868-025-00947-7Spinal cord injuryBody weight-supported treadmill trainingGlial scarAstrocyte reactivityMatrix metalloproteinase-2/9
spellingShingle Jili Cai
Yu Wang
Chenyuan Zhai
Kunmao Jiang
Zun Wang
Lu Fang
Xiangzhe Li
Chenchen Zhu
Wentao Liu
Tong Wang
Qi Wu
Body weight-supported treadmill training reduces glial scar overgrowth in SCI rats by decreasing the reactivity of astrocytes during the subacute phase
BMC Neuroscience
Spinal cord injury
Body weight-supported treadmill training
Glial scar
Astrocyte reactivity
Matrix metalloproteinase-2/9
title Body weight-supported treadmill training reduces glial scar overgrowth in SCI rats by decreasing the reactivity of astrocytes during the subacute phase
title_full Body weight-supported treadmill training reduces glial scar overgrowth in SCI rats by decreasing the reactivity of astrocytes during the subacute phase
title_fullStr Body weight-supported treadmill training reduces glial scar overgrowth in SCI rats by decreasing the reactivity of astrocytes during the subacute phase
title_full_unstemmed Body weight-supported treadmill training reduces glial scar overgrowth in SCI rats by decreasing the reactivity of astrocytes during the subacute phase
title_short Body weight-supported treadmill training reduces glial scar overgrowth in SCI rats by decreasing the reactivity of astrocytes during the subacute phase
title_sort body weight supported treadmill training reduces glial scar overgrowth in sci rats by decreasing the reactivity of astrocytes during the subacute phase
topic Spinal cord injury
Body weight-supported treadmill training
Glial scar
Astrocyte reactivity
Matrix metalloproteinase-2/9
url https://doi.org/10.1186/s12868-025-00947-7
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