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Treadmill Exercise Decreases Inflammation Via Modulating IL-6 Expression in the Rat Model of Middle Cerebral Artery Occlusion

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Abstract

Background

Long-term bed rest in neurointensive care (NIC) patients leads to skeletal muscle atrophy and cognitive dysfunction, which seriously affects the physical fitness and final prognosis of critically ill patients. Exercise therapy plays an increasingly important role in the treatment and rehabilitation of patients with sarcopenia. However, the therapeutic effect and mechanism of exercise therapy for patients with neurological impairment remain unclear.

Methods

Serum samples of NIC patients before and after exercise therapy and normal people were collected to detect interleukin-6 (IL-6) and interleukin-1β levels by enzyme-linked immunosorbent assay (ELISA). Middle cerebral artery occlusion (MCAO) was used for the construction of a rat model. The Morris water maze test, exploration test, and open-field test were used to assess neurological function in rats. Western blot and quantitative real-time polymerase chain reaction were performed to evaluate the activation of IL-6/adenosine-monophosphate-activated protein kinase (AMPK) signaling.

Results

Exercise therapy attenuated IL-6 expression in NIC patients. Exercise therapy alleviated cognitive dysfunctions and decreased IL-6 expression in MCAO rats. Exercise therapy alleviated gastrocnemius muscle injury in rats after MCAO by modulating IL-6/AMPK signaling.

Conclusions

Treadmill exercise decreases inflammation in MCAO rats via modulating IL-6/AMPK signaling.

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References

  1. Robba C, Wong A, Poole D, et al. Basic ultrasound head-to-toe skills for intensivists in the general and neuro intensive care unit population: consensus and expert recommendations of the European Society of Intensive Care Medicine. Intensive Care Med. 2021;47:1347–67.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Beckham JD, Tyler KL. Neuro-intensive care of patients with acute CNS infections. Neurotherapeutics. 2012;9:124–38.

    Article  PubMed  Google Scholar 

  3. Gomes MJ, Martinez PF, Pagan LU, et al. Skeletal muscle aging: influence of oxidative stress and physical exercise. Oncotarget. 2017;8:20428–40.

    Article  PubMed  PubMed Central  Google Scholar 

  4. von Haehling S. The wasting continuum in heart failure: from sarcopenia to cachexia. Proc Nutr Soc. 2015;74:367–77.

    Article  Google Scholar 

  5. Souza RW, Piedade WP, Soares LC, et al. Aerobic exercise training prevents heart failure-induced skeletal muscle atrophy by anti-catabolic, but not anabolic actions. PLoS ONE. 2014;9: e110020.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Tzanis G, Philippou A, Karatzanos E, et al. Effects of high-intensity interval exercise training on skeletal myopathy of chronic heart failure. J Card Fail. 2017;23:36–46.

    Article  PubMed  Google Scholar 

  7. Cai M, Wang Q, Liu Z, et al. Effects of different types of exercise on skeletal muscle atrophy, antioxidant capacity and growth factors expression following myocardial infarction. Life Sci. 2018;213:40–9.

    Article  CAS  PubMed  Google Scholar 

  8. Lenk K, Erbs S, Hollriegel R, et al. Exercise training leads to a reduction of elevated myostatin levels in patients with chronic heart failure. Eur J Prev Cardiol. 2012;19:404–11.

    Article  PubMed  Google Scholar 

  9. Ribeiro-Samora GA, Rabelo LA, Ferreira ACC, et al. Inflammation and oxidative stress in heart failure: effects of exercise intensity and duration. Braz J Med Biol Res. 2017;50: e6393.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Carling D. AMPK signalling in health and disease. Curr Opin Cell Biol. 2017;45:31–7.

    Article  CAS  PubMed  Google Scholar 

  11. Thomson DM, Gordon SE. Diminished overload-induced hypertrophy in aged fast-twitch skeletal muscle is associated with AMPK hyperphosphorylation. J Appl Physiol. 1985;2005(98):557–64.

    Google Scholar 

  12. Nakashima K, Yakabe Y. AMPK activation stimulates myofibrillar protein degradation and expression of atrophy-related ubiquitin ligases by increasing FOXO transcription factors in C2C12 myotubes. Biosci Biotechnol Biochem. 2007;71:1650–6.

    Article  CAS  PubMed  Google Scholar 

  13. Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell. 2004;117:399–412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Mammucari C, Schiaffino S, Sandri M. Downstream of Akt: FoxO3 and mTOR in the regulation of autophagy in skeletal muscle. Autophagy. 2008;4:524–6.

    Article  CAS  PubMed  Google Scholar 

  15. Haymore JB, Patel N. Delirium in the neuro intensive care unit. Crit Care Nurs Clin North Am. 2016;28:21–35.

    Article  PubMed  Google Scholar 

  16. Hutchens MP, Memtsoudis S, Sadovnikoff N. Propofol for sedation in neuro-intensive care. Neurocrit Care. 2006;4:54–62.

    Article  CAS  PubMed  Google Scholar 

  17. Mercuri E, Finkel RS, Muntoni F, et al. Diagnosis and management of spinal muscular atrophy: part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord. 2018;28:103–15.

    Article  PubMed  Google Scholar 

  18. Pincherle A, Johr J, Pancini L, et al. Intensive care admission and early neuro-rehabilitation. Lessons for COVID-19? Front Neurol. 2020;11:880.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Soares MN, Eggelbusch M, Naddaf E, et al. Skeletal muscle alterations in patients with acute Covid-19 and post-acute sequelae of Covid-19. J Cachexia Sarcopenia Muscle. 2022;13:11–22.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Herzig S, Shaw RJ. AMPK: guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018;19:121–35.

    Article  CAS  PubMed  Google Scholar 

  21. McArthur S, Juban G, Gobbetti T, et al. Annexin A1 drives macrophage skewing to accelerate muscle regeneration through AMPK activation. J Clin Invest. 2020;130:1156–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Thomson DM. The role of AMPK in the regulation of skeletal muscle size, hypertrophy, and regeneration. Int J Mol Sci. 2018;19:3125.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Chen X, Guo Y, Jia G, et al. Arginine promotes skeletal muscle fiber type transformation from fast-twitch to slow-twitch via Sirt1/AMPK pathway. J Nutr Biochem. 2018;61:155–62.

    Article  CAS  PubMed  Google Scholar 

  24. Choi S, Jeong HJ, Kim H, et al. Skeletal muscle-specific Prmt1 deletion causes muscle atrophy via deregulation of the PRMT6-FOXO3 axis. Autophagy. 2019;15:1069–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Fan J, Yang X, Li J, et al. Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway. Oncotarget. 2017;8:17475–90.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Morris BJ, Willcox DC, Donlon TA, et al. FOXO3: a major gene for human longevity–a mini-review. Gerontology. 2015;61:515–25.

    Article  CAS  PubMed  Google Scholar 

  27. Yao S, Fan LY, Lam EW. The FOXO3-FOXM1 axis: a key cancer drug target and a modulator of cancer drug resistance. Semin Cancer Biol. 2018;50:77–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mammucari C, Milan G, Romanello V, et al. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab. 2007;6:458–71.

    Article  CAS  PubMed  Google Scholar 

  29. Fitzwalter BE, Thorburn A. FOXO3 links autophagy to apoptosis. Autophagy. 2018;14:1467–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Schiaffino S, Dyar KA, Ciciliot S, et al. Mechanisms regulating skeletal muscle growth and atrophy. FEBS J. 2013;280:4294–314.

    Article  CAS  PubMed  Google Scholar 

  31. Skurk C, Izumiya Y, Maatz H, et al. The FOXO3a transcription factor regulates cardiac myocyte size downstream of AKT signaling. J Biol Chem. 2005;280:20814–23.

    Article  CAS  PubMed  Google Scholar 

  32. Raue U, Slivka D, Jemiolo B, et al. Proteolytic gene expression differs at rest and after resistance exercise between young and old women. J Gerontol A Biol Sci Med Sci. 2007;62:1407–12.

    Article  PubMed  Google Scholar 

  33. Léger B, Cartoni R, Praz M, et al. Akt signalling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. J Physiol. 2006;576:923–33.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Stefanetti RJ, Voisin S, Russell A, et al. Recent advances in understanding the role of FOXO3. F1000Res. 2018;7:1372.

    Article  Google Scholar 

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Authors and Affiliations

Authors

Contributions

HF, YQ, XW, FC, and XL did the experiments, collected and analyzed the data, and wrote the manuscript. HF and XL conceived and coordinated the study.

Corresponding author

Correspondence to Hui Feng.

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Conflict of interest

Hui Feng, Yinliang Qi, Xinlong Wang, Fangyu Chen, and Xueping Li declare that they have no competing interest.

Ethical Approval

The study was approved by the Ethics Committee of The Affiliated Jiangning Hospital of Nanjing Medical University.

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Feng, H., Qi, Y., Wang, X. et al. Treadmill Exercise Decreases Inflammation Via Modulating IL-6 Expression in the Rat Model of Middle Cerebral Artery Occlusion. Neurocrit Care 38, 279–287 (2023). https://doi.org/10.1007/s12028-022-01575-3

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  • DOI: https://doi.org/10.1007/s12028-022-01575-3

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