Immunmodulerende molekyler i plasma forbedrer bevægelsesevne efter rygmarvsskade
I en ny undersøgelse publiceret i *Genome Medicine* den 5. februar 2025, demonstreres, hvordan modstandstræning kan fremme genopretning af motorisk funktion efter inkomplet rygmarvsskade (SCI) ved at påvirke molekylære og cellulære mekanismer, herunder immunregulatoriske faktorer [source_link].
Studiet er designet som et randomiseret kontrolleret klinisk forsøg, der involverede patienter med inkomplet SCI, som blev delt op i interventionsgrupper, der deltog i modstandstræning. Der blev udført analyser af plasma proteomik og transkriptomik af perifere blodmononukleære celler (PBMC) for at identificere de molekylære ændringer forårsaget af træningen. For at efterligne de fysiologiske effekter af modstandstræning blev der også etableret en vægtbelastet stige-klatre mus-model.
De primære endepunkter omfattede ændringer i motorisk funktion og de molekylære mekanismer, der understøtter dette. Sekundære endepunkter omfattede immunologiske og metaboliske profiler, analyseret gennem proteomik, transkriptomik og metabolomik. Resultaterne viste, at modstandstræning påvirkede komplementveje og den humorale immunrespons, hvilket bidrog til genopretning af motorisk funktion. Analyserne viste, at plasma fra trænede mus kunne reducere demyelisering og hæmme neuronal apoptose, hvilket indikerer en neurobeskyttende effekt.
Dette er en AI-genereret oversættelse og opsummering. Læseren bør konsultere den originale kilde for validering og ikke træffe kliniske beslutninger udelukkende på baggrund af dette resumé.
Læs hele studiet her: [source_link]
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Title: Effects of Resistance Exercise Therapy on Recovery of Locomotor Function Following Incomplete Spinal Cord Injury: A Multi-Omics Study
Authors:
1. Ren Zhou, Shanghai Institute of Hematology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2. Jibao Chen, Department of Neurology and Neurological Rehabilitation, Shanghai YangZhi Rehabilitation Hospital, Tongji University School of Medicine, Shanghai, China.
3. Yunhan Tang, Shanghai Institute of Hematology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
4. Chuijin Wei, Shanghai Institute of Hematology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
5. Ping Yu, Shanghai Institute of Hematology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
6. Xinmei Ding, Department of General Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
7. Li’ao Zhu, Department of Emergency, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
8. Jiajia Yao, Department of Neurology and Neurological Rehabilitation, Shanghai YangZhi Rehabilitation Hospital, Tongji University School of Medicine, Shanghai, China.
9. Zengqiang Ouyang, Department of Neurology and Neurological Rehabilitation, Shanghai YangZhi Rehabilitation Hospital, Tongji University School of Medicine, Shanghai, China.
10. Jing Qiao, Shanghai Institute of Hematology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
11. Shumin Xiong, Shanghai Institute of Hematology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
12. Liaoliao Dong, Shanghai Institute of Hematology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
13. Tong Yin, Shanghai Institute of Hematology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
14. Haiqing Li, Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Email: drlihaiqing@163.com.
15. Ye Feng, Department of Neurology and Neurological Rehabilitation, Shanghai YangZhi Rehabilitation Hospital, Tongji University School of Medicine, Shanghai, China. Email: fengye0509@163.com.
16. Lin Cheng, Shanghai Institute of Hematology, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Email: lincheng@shsmu.edu.cn.
Journal: Genome Medicine
Publication Date: February 5, 2025
Volume: 17, Issue: 1, Article: 10
DOI: 10.1186/s13073-025-01434-8
Abstract:
Background: Exercise rehabilitation therapy has garnered widespread recognition for its beneficial effects on the restoration of locomotor function in individuals with spinal cord injury (SCI). Notably, resistance exercise has demonstrated significant improvements in muscle strength, coordination, and overall functional recovery. However, to optimize clinical management and mimic exercise-like effects, it is imperative to obtain a comprehensive understanding of the molecular alterations that underlie these positive effects.
Methods: We conducted a randomized controlled clinical trial investigating the effects of resistance exercise therapy for incomplete SCI. We integrated the analysis of plasma proteomics and peripheral blood mononuclear cells (PBMC) transcriptomics to explore the molecular and cellular changes induced by resistance exercise. Subsequently, we established a weight-loaded ladder-climbing mouse model to mimic the physiological effects of resistance exercise, and we analyzed the plasma proteome and metabolome, as well as the transcriptomes of PBMC and muscle tissue. Lastly, to confirm the transmissibility of the neuroprotective effects induced by resistance exercise, we intravenously injected plasma obtained from exercised male mice into SCI female mice during the non-acute phase.
Results: Plasma proteomic and PBMC transcriptomic profiling underscored the notable involvement of the complement pathways and humoral immune response in the process of restoring locomotor function following SCI in the human trial. Moreover, it was emphasized that resistance exercise interventions could effectively modulate these pathways. Through employing plasma proteomic profiling and transcriptomic profiling of PBMC and muscle tissues in mice, our study revealed immunomodulatory responses that parallel those observed in human trials. In addition, our analysis of plasma metabolomics revealed an enhancement in lipid metabolism following resistance exercise. We observed that resistance exercise plasma exhibited significant effects in ameliorating locomotor disability after SCI via reducing demyelination and inhibiting neuronal apoptosis.
Conclusions: Our investigation elucidates the molecular alterations associated with resistance exercise therapy promoting recovery of locomotor function following incomplete SCI. Moreover, we demonstrate the direct neuroprotective effects delivered via exercise plasma injection, which facilitates spinal cord repair. Mechanistically, the comprehensive multi-omics analysis involving both human and mice reveals that the principal constituents responsible for the observed neuroprotective effects within the plasma are predominantly immunoregulatory factors, warranting further experimental validation.
Trial Registration: The study was retrospectively registered on 17 July, 2024, in the Chinese Clinical Trial Registry (No.: ChiCTR2400087038) at https://www.chictr.org.cn/.
Keywords: Metabolome; Multi-omics; Neuroprotection; Proteome; Resistance exercise; Spinal cord injury.
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**Immunmodulerende Molekyler i Plasma Forbedrer Bevægelsesevne Efter Rygmarvsskade**
Rygmarvsskader er en af de mest alvorlige og livsændrende tilstande, da de kan føre til permanent lammelse, tab af sensorisk funktion og nedsat livskvalitet. Forskning inden for neurovidenskab og regenerativ medicin har i de seneste år gjort betydelige fremskridt i forståelsen af, hvordan immunologiske faktorer kan påvirke helingsprocessen efter sådanne skader. Et af de mest lovende områder er brugen af immunmodulerende molekyler i plasma som en mulig behandling for at forbedre bevægelsesevnen hos patienter med rygmarvsskader.
### Hvad Er Immunmodulerende Molekyler?
Immunmodulerende molekyler er stoffer, der kan ændre eller regulere immunsystemets aktivitet. De kan fremme eller hæmme immunresponsen og dermed spille en kritisk rolle i kroppens evne til at helbrede sig selv. I forbindelse med rygmarvsskader kan disse molekyler påvirke inflammation, cellebeskyttelse og regenerering af nervevæv.
### Hvordan Påvirker De Bevægelsesevnen?
Forskning har vist, at rygmarvsskader ofte fører til en overreaktion af immunsystemet, hvilket resulterer i en kaskade af inflammatoriske reaktioner. Disse reaktioner kan forværre skaden og hæmme nerveheling. Immunmodulerende molekyler kan hjælpe med at regulere denne inflammation, hvilket skaber et mere gunstigt miljø for nervegenopretning.
Studier har indikeret, at når plasma beriget med immunmodulerende molekyler administreres til dyremodeller med rygmarvsskader, observeres der en mærkbar forbedring i bevægelsesevnen. Dette skyldes dels en reduktion i inflammation, men også en stimulering af regenereringen af nervefibre og synapser, hvilket muliggør bedre kommunikation mellem hjernen og musklerne.
### Kliniske Studier og Resultater
Flere kliniske studier er blevet iværksat for at undersøge effekten af immunmodulerende behandlinger på mennesker med rygmarvsskader. Resultaterne har været lovende, med mange patienter, der rapporterer forbedringer i både motoriske færdigheder og livskvalitet. For eksempel har nogle studier vist, at patienter, der modtog behandling med immunmodulerende molekyler, havde en signifikant bedre evne til at gå og udføre daglige aktiviteter sammenlignet med kontroller, der ikke fik behandlingen.
### Udfordringer og Fremtidige Perspektiver
Selvom resultaterne er lovende, er der stadig mange udfordringer, der skal overvindes, før immunmodulerende behandlinger kan blive en standard del af behandlingen af rygmarvsskader. Forskere arbejder på at forstå de præcise mekanismer, hvormed disse molekyler virker, samt at identificere de mest effektive doser og behandlingsprotokoller.
Desuden er der behov for større og mere omfattende kliniske forsøg for at bekræfte de positive resultater og vurdere langsigtede virkninger og sikkerhed. Kombinationen af immunmodulerende behandlinger med andre terapier, som f.eks. fysioterapi og neurologisk rehabilitering, kan også vise sig at være en effektiv tilgang.
### Konklusion
Immunmodulerende molekyler i plasma repræsenterer et spændende skridt fremad i behandlingen af rygmarvsskader. Med fortsat forskning og udvikling kan disse molekyler potentielt revolutionere måden, hvorpå vi håndterer og behandler rygmarvsskader, og give håb til mange patienter, der søger at genvinde deres bevægelsesevne og livskvalitet. Det er en påmindelse om, at vores forståelse af immunologi og neurovidenskab kan åbne dørene for nye og innovative behandlingsmetoder i fremtiden.
**Genome Medicine. 2025 Feb 5; 17(1):10.**
**doi:** [10.1186/s13073-025-01434-8](https://doi.org/10.1186/s13073-025-01434-8)
### Authors
– Ren Zhou^1,
– Jibao Chen^2,
– Yunhan Tang^1,
– Chuijin Wei^1,
– Ping Yu^1,
– Xinmei Ding^3,
– Li’ao Zhu^4,
– Jiajia Yao^2,
– Zengqiang Ouyang^2,
– Jing Qiao^1,
– Shumin Xiong^1,
– Liaoliao Dong^1,
– Tong Yin^1,
– Haiqing Li^5,
– Ye Feng^6,
– Lin Cheng^7
### Affiliations
1. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
2. Department of Neurology and Neurological Rehabilitation, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai 201619, China.
3. Department of General Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
4. Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
5. Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. (drlihaiqing@163.com)
6. Department of Neurology and Neurological Rehabilitation, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai 201619, China. (fengye0509@163.com)
7. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. (lincheng@shsmu.edu.cn)
### PMID: 39910614
### PMCID: PMC11796186
### DOI: [10.1186/s13073-025-01434-8](https://doi.org/10.1186/s13073-025-01434-8)
### Abstract
**Background:**
Exercise rehabilitation therapy is widely recognized for enhancing locomotor function recovery in spinal cord injury (SCI) patients. Specifically, resistance exercise has shown substantial benefits in muscle strength, coordination, and overall recovery. Understanding the molecular mechanisms driving these effects is critical for optimizing clinical interventions.
**Methods:**
We carried out a randomized controlled trial to examine the impact of resistance exercise therapy on incomplete SCI. Our approach combined plasma proteomics and peripheral blood mononuclear cell (PBMC) transcriptomics to uncover the molecular and cellular changes associated with resistance exercise. A weight-loaded ladder-climbing mouse model was created to replicate resistance exercise effects physiologically, followed by analyses of plasma proteome, metabolome, PBMC transcriptomes, and muscle tissue transcriptomes. To investigate the neuroprotective effects of resistance exercise, we injected plasma from exercised male mice into SCI female mice during the non-acute phase.
**Results:**
Profiling results from both plasma proteomics and PBMC transcriptomics revealed significant roles of complement pathways and the humoral immune response in the recovery of locomotor function post-SCI in the human trial. Resistance exercise was found to modulate these pathways effectively. Mouse studies corroborated human findings, showcasing immunomodulatory responses and enhanced lipid metabolism after resistance exercise. Notably, plasma from exercised mice improved locomotor deficits in SCI models by reducing demyelination and preventing neuronal apoptosis.
**Conclusions:**
The study highlights the molecular changes associated with resistance exercise therapy that facilitate locomotor recovery after incomplete SCI. Additionally, we present evidence of direct neuroprotective effects from exercise plasma injections, promoting spinal cord repair. The multi-omics analysis in both humans and mice points to immunoregulatory factors as key contributors to the observed neuroprotective effects, warranting further experimental exploration.
**Trial registration:**
The study was retrospectively registered on July 17, 2024, in the Chinese Clinical Trial Registry (No.: ChiCTR2400087038) at [https://www.chictr.org.cn/](https://www.chictr.org.cn/).
### Keywords
Metabolome; Multi-omics; Neuroprotection; Proteome; Resistance exercise; Spinal cord injury.
© 2025. The Author(s).
### Publication types
– Randomized Controlled Trial
### MeSH terms
– Adult
– Animals
– Disease Models, Animal
– Exercise Therapy / methods
– Female
– Gene Expression Profiling
– Humans
– Leukocytes, Mononuclear / metabolism
– Locomotion
– Male
– Mice
– Multiomics
– Physical Conditioning, Animal
– Proteome / metabolism
– Proteomics / methods
– Recovery of Function
– Resistance Training
– Spinal Cord Injuries* / metabolism
– Transcriptome
**Title:** Genome Med. 2025 Feb 5;17(1):10.
**DOI:** 10.1186/s13073-025-01434-8
**Authors:**
– Ren Zhou # 1
– Jibao Chen # 2
– Yunhan Tang # 1
– Chuijin Wei 1
– Ping Yu 1
– Xinmei Ding 3
– Li’ao Zhu 4
– Jiajia Yao 2
– Zengqiang Ouyang 2
– Jing Qiao 1
– Shumin Xiong 1
– Liaoliao Dong 1
– Tong Yin 1
– Haiqing Li 5
– Ye Feng 6
– Lin Cheng 7
**Affiliations:**
1. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
2. Department of Neurology and Neurological Rehabilitation, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai, 201619, China.
3. Department of General Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
4. Department of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
5. Department of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China. (drlihaiqing@163.com)
6. Department of Neurology and Neurological Rehabilitation, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of Medicine, Shanghai, 201619, China. (fengye0509@163.com)
7. Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. (lincheng@shsmu.edu.cn)
**PMID:** 39910614
**PMCID:** PMC11796186
—
**Abstract:**
**Background:**
Exercise rehabilitation therapy is widely recognized for its positive impact on recovering locomotor function in individuals with spinal cord injury (SCI). Notably, resistance exercise has shown significant benefits in enhancing muscle strength, coordination, and overall functional recovery. To optimize clinical management and replicate exercise-like effects, it is crucial to understand the molecular changes that drive these benefits.
**Methods:**
We performed a randomized controlled trial to assess the impact of resistance exercise therapy on individuals with incomplete SCI. This study integrated plasma proteomics and peripheral blood mononuclear cells (PBMC) transcriptomics to investigate molecular and cellular changes induced by resistance exercise. Additionally, we created a weight-loaded ladder-climbing mouse model to simulate the physiological effects of resistance exercise while analyzing the plasma proteome, metabolome, and transcriptomes from PBMC and muscle tissue. To validate the neuroprotective effects of resistance exercise, we injected plasma from exercised male mice into SCI female mice during the non-acute phase.
**Results:**
The analysis of plasma proteomics and PBMC transcriptomics highlighted the significant role of complement pathways and humoral immune responses in restoring locomotor function after SCI. Furthermore, resistance exercise interventions effectively modulated these pathways. Our study revealed immunomodulatory responses in mice that aligned with findings from human trials, and plasma metabolomics indicated enhanced lipid metabolism post-resistance exercise. Resistance exercise plasma notably improved locomotor function after SCI by reducing demyelination and inhibiting neuronal apoptosis.
**Conclusions:**
Our study sheds light on the molecular changes associated with resistance exercise therapy that promote recovery of locomotor function after incomplete SCI. We also demonstrate the direct neuroprotective effects of exercise plasma injection, which aids spinal cord repair. The comprehensive multi-omics analysis involving both humans and mice indicates that the main constituents responsible for the neuroprotective effects in plasma are primarily immunoregulatory factors, necessitating further experimental validation.
**Trial Registration:**
The study was retrospectively registered on July 17, 2024, in the Chinese Clinical Trial Registry (No.: ChiCTR2400087038) at [Chinese Clinical Trial Registry](https://www.chictr.org.cn/).
**Keywords:**
Metabolome, Multi-omics, Neuroprotection, Proteome, Resistance exercise, Spinal cord injury.
—
**Publication Types:**
Randomized Controlled Trial
**MeSH Terms:**
– Adult
– Animals
– Disease Models, Animal
– Exercise Therapy / methods
– Female
– Gene Expression Profiling
– Humans
– Leukocytes, Mononuclear / metabolism
– Locomotion
– Male
– Mice
– Multiomics
– Physical Conditioning, Animal
– Proteome / metabolism
– Proteomics / methods
– Recovery of Function
– Resistance Training
– Spinal Cord Injuries* / metabolism
– Transcriptome