Ischemic stroke rehabilitation through endurance training of varying intensity and duration in male sprague-dawley rats

Articles in Press

Document Type : Original Article

Authors

1 Department of Biological Sciences in Sport and Health, Faculty of Sport Science and Health, Shahid Beheshti University, Tehran, Iran

2 Department of Kinesiology and Physical Education, McGill University, Montréal, Quebec, Canada

3 Department of Kinesiology and Recreation Management, University of Manitoba, Winnipeg, Manitoba, Canada

10.22038/ijbms.2025.86115.18602

Abstract

Objective(s): This research aimed to investigate the effect of 2 types of exercise on apoptosis, neurogenesis, and angiogenesis factors in the penumbra area of stroke during the rehabilitation period after stroke. 
Materials and Methods: A transient distal middle cerebral artery occlusion (td-MCAO) model was used to induce stroke and after that, the animals were randomly divided into three groups: stroke, stroke + continuous exercise with increasing duration (CTID), and stroke + exercise with increasing intensity (CTII). At 24 hr spost-stroke , MRA, neurological deficit, and behavioral tests were conducted, and also continuous exercises were conducted  for five consecutive days, Finally, MRI and behavioral tests were performed, and 24 hr after that, tissue separation and blood sampling were performed to evaluate plasma irisin, Extracellular Signal-Regulated Kinases 1 and 2 (ERK1/2) / cAMP Response Element-Binding Protein (CREB) / 90 kDa Ribosomal S6 Kinase (P90RSK) pathway, Vascular Endothelial Growth Factor (VEGF) / Vascular Endothelial Growth Factor Receptor 2 (VEGF-R2), and Brain-Derived Neurotrophic Factor  (BDNF) / Tropomyosin Receptor Kinase B (TrKB) levels. for statistical analysis, one-way and two-way ANOVA tests were used at the significance level of P<0.05.
Results: Both training models reduced the volume of stroke and neurological defects compared to the stroke group (P<0.05), while the amounts of irisin and CREB in the CTID group increased significantly compared to the CTII and stroke groups (P<0.01). VEGFR2 values in training groups increased significantly compared to the stroke group (P<0.05) but in the CTII group, VEGFR2 values increased significantly compared to the CTID group (P<0.05).
Conclusion: The findings of the present study showed it seems that doing exercises with moderate intensities and gradually increasing the duration of exercise in the acute phase after stroke can be considered a suitable treatment in future research.

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References

1. Leitch S, Logan M, Beishon L, Quinn TJ. International research priority setting exercises in stroke: A systematic review. Int J Stroke 2023;18:133–143.
2. Cooke EV, Mares K, Clark A, Tallis RC, Pomeroy VM. The effects of increased dose of exercise-based therapies to enhance motor recovery after stroke:A systematic review and meta-analysis. BMC Med 2010;8:1-13.
3. Crozier J, Roig M, Eng JJ, MacKay-Lyons M, Fung J, Ploughman M, et al. High-intensity interval training after stroke: An opportunity to promote functional recovery, cardiovascular health, and neuroplasticity. Neurorehabil Neural Repair 2018;32:543-556.
4. Rankovic M, Jakovljevic V, Bradic J, Jakovljevic B, Zivkovic V, Srejovic I, et al. Effects of high intensity interval vs endurance training on cardiac parameters in ischemia/reperfusion of male rats: focus on oxidative stress. Front Physiol 2021;12:534127.
5. Li F, Geng X, Huber C, Stone C, Ding Y. In search of a dose: The functional and molecular effects of exercise on poststroke rehabilitation in rats. Front Cell Neurosci 2020;14:186-197.
6. Geng H, Li M, Tang J, Lv Q, Li R, Wang L. Early rehabilitation exercise after stroke improves neurological recovery through enhancing angiogenesis in patients and cerebral ischemia rat model. Int J Mol Sci 2022;23:10508-10523.
7. Fasihiyan M, Nourshahi M. Continuous exercises with different intensities and effectiveness on the anti-apoptotic BAX/BCL-2/Caspase-3 pathway in the rehabilitation period after stroke in male Sprague-Dawley rats. Sport Physiol 2023;15:87–106.
8. Church G, Smith C, Ali A, Sage K. What is intensity and how can it benefit exercise intervention in people with stroke? a rapid review. Front Rehabil Sci 2021;2:722668.
9. Lee THY, Formolo DA, Kong T, Lau SWY, Ho CSL, Leung RYH, et al. Potential exerkines for physical exercise-elicited pro-cognitive effects: Insight from clinical and animal research. Int Rev Neurobiol 2019;147:361-395.
10. Kang D, Park J, Eun SD. The efficacy of community-based exercise programs on circulating irisin level, muscle strength, cardiorespiratory endurance, and body composition for ischemic stroke: A randomized controlled trial. Front Neurol 2023;14:1187666.
11. Zhang Y, Zhang X, Lin S. Irisin: A bridge between exercise and neurological diseases. Heliyon 2022;8:1-6.
12. Inyushkin AN, Poletaev VS, Inyushkina EM, Kalberdin IS, Inyushkin AA. Irisin/BDNF signaling in the muscle-brain axis and circadian system: A review. J Biomed Res 2024;38:1-16.
13. Li S, Peng T, Zhao X, Silva M, Liu L, Zhou W, et al. Artemether confers neuroprotection on cerebral ischemic injury through stimulation of the Erk1/2-P90rsk-CREB signaling pathway. Redox Biol 2021;46:102069.
14. Geng X, Wang Q, Lee H, Huber C, Wills M, Elkin K, et al. Remote ischemic postconditioning vs physical exercise after stroke: an alternative rehabilitation strategy? Mol Neurobiol 2021;58:3141-3157.
15. Liu H, Zhong L, Zhang Y, Liu X, Li J. Rutin attenuates cerebral ischemia–reperfusion injury in ovariectomized rats via estrogen-receptor-mediated BDNF–TrkB and NGF–TrkA signaling. Biochem Cell Biol 2018;96:672-681.
16. Yang Y, Torbey MT. Angiogenesis and blood-brain barrier permeability in vascular remodeling after stroke. Curr Neuropharmacol 2020;18:1250-1265.
17. Kucherova K, Koroleva E, Alifirova V. The role of VEGF in angiogenesis and motor recovery after ischemic stroke. Neurochem J 2023;17:528-533.
18. Taheri M, Ebrahim K, Nemati J. The effect of precondition with continuous and high-intensity interval training on angiogenic factors in the td-MCAO stroke model. Sport Physiol 2023;59:97-114.
19. Nasoohi S, Ghahremani PT, Alehossein P, Elyasizadeh S, BaniArdalan S, Ismael S, et al. The p75 neurotrophin receptor inhibitor, LM11A-31, ameliorates acute stroke injury and modulates astrocytic proNGF. Exp Neurol 2023;359:114161.
20. Althurwi HN, Abdel-Rahman RF, Soliman GA, Ogaly HA, Alkholifi FK, Abd-Elsalam RM, et al. Protective effect of beta-carotene against myeloperoxidase-mediated oxidative stress and inflammation in rat ischemic brain injury. Antioxidants 2022;11:2344-2360.
21. Li C, Ke C, Su Y, Wan C. Exercise intervention promotes the growth of synapses and regulates neuroplasticity in rats with ischemic stroke through exosomes. Front Neurol 2021;12:752595.
22. Zhang Q, Wu JF, Shi QL, Li MY, Wang CJ, Wang X, et al. The neuronal activation of deep cerebellar nuclei is essential for environmental enrichment-induced post-stroke motor recovery. Aging Dis 2019;10:530-542.
23. Gono R, Sugimoto K, Yang C, Murata Y, Nomura R, Shirazaki M, et al. Molecular mechanism of cerebral edema improvement via IL-1RA released from the stroke-unaffected hindlimb by treadmill exercise after cerebral infarction in rats. J Cereb Blood Flow Metab 2023;43:812-827.
24. Sun J, Ke Z, Yip SP, Hu XL, Zheng XX, Tong KY. Gradually increased training intensity benefits rehabilitation outcome after stroke by BDNF upregulation and stress suppression. Biomed Res Int 2014;2014:871916.
25. Li F, Shi W, Zhao EY, Geng X, Li X, Peng C, et al. Enhanced apoptosis from early physical exercise rehabilitation following ischemic stroke. J Neurosci Res 2017;95:1017-1024.
26. Tani A, Sakakima H, Otsuka S, Mizuno K, Nakanishi K, Norimatsu K, et al. Stimulation of functional recovery via neurorepair mechanisms by the traditional Japanese Kampo medicine, Ninjin’yoeito, and physical exercise in a rat ischemic stroke model. J Ethnopharmacol 2023;302:115927.
27. Liu Y, Zhu C, Guo J, Chen Y, Meng C. The neuroprotective effect of irisin in ischemic stroke. Front Aging Neurosci 2020;12:588958.
28. Asadi Y, Gorjipour F, Behrouzifar S, Vakili A. Irisin peptide protects brain against ischemic injury through reducing apoptosis and enhancing BDNF in a rodent model of stroke. Neurochem Res 2018;43:1549-1560.
29. Yani S, Harris S, Jusuf AA, Goenarjo R, Makkiyah FA, Sabita R, Ibrahim N. Effect of the high-intensity interval training on BDNF level in ischemic stroke rat model on the recovery of motor function. Indones Biomed J 2024;16:152-161.
30. Li DJ, Li YH, Yuan HB, Qu LF, Wang P. The novel exercise-induced hormone irisin protects against neuronal injury via activation of the Akt and ERK1/2 signaling pathways and contributes to the neuroprotection of physical exercise in cerebral ischemia. Metabolism 2017;68:31-42.
31. Tang XQ, Liao RY, Zheng LJ, Yang LL, Ma ZL, Yi C, et al. Aerobic exercise reverses the NF-κB/NLRP3 inflammasome/5-HT pathway by upregulating irisin to alleviate post-stroke depression. Ann Transl Med 2022;12:128-129.
32. Leger C, Quirié A, Méloux A, Fontanier E, Chaney R, Basset C, et al. Impact of exercise intensity on cerebral BDNF levels: Role of FNDC5/irisin. Int J Mol Sci 2024;25:1213-1228.
33. Hugues N, Pin-Barre C, Brioche T, Pellegrino C, Berton E, Rivera C, Laurin J. High-intensity training with short and long intervals regulate cortical neurotrophic factors, apoptosis markers and chloride homeostasis in rats with stroke. Physiol Behav 2023;266:114190.
34. Lee SS, Kim CJ, Shin MS, Lim BV. Treadmill exercise ameliorates memory impairment through ERK-Akt-CREB-BDNF signaling pathway in cerebral ischemia gerbils. J Exerc Rehabil 2020;16:49-57.
Iranian Journal of Basic Medical Sciences

Articles in Press, Accepted Manuscript
Available Online from 08 July 2025

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