Physical Exercise and Wet Cupping Therapy Stimulate Neural Stem Cells in Animal Model of Ischemic Stroke
Abstract
The process of neuroplasticity in stroke recovery remains poorly understood. SRY-related HMG-box 2 (SOX2), a protein that plays a role in controlling neural stem cell (NSC) proliferation and differentiation, is of particular interest. This research seeks to investigate how exercise and wet cupping therapy affect SOX2 expression in animal models of stroke, which are created using unilateral common carotid artery occlusion (UCCAO). The study utilized a control group design with a post-test evaluation. Thirty-six Wistar rats, aged 3 months, were randomly divided into six groups of equal size: control (n=6), stroke (n=6), cupping (n=6), exercise (n=6), stroke plus cupping (n=6), and stroke plus exercise (n=6). Wet cupping therapy was performed twice a week for three weeks. The exercise included a 20-minute swimming activity scheduled daily. This swimming exercise was performed three times a week for three weeks. Analysis of multiple comparisons among groups employing the ANOVA test proved that SOX2 expression in both the stroke plus exercise group and the stroke plus cupping group was significantly elevated. The stroke group was significantly lower than the control group. This study highlights the potential of physical exercise and wet cupping therapy to upregulate SOX2 expression in a UCCAO-induced brain injury model, supporting their role as promising alternative neuroregenerative interventions.
Ju YW, Lee JS, Choi Y-A, Kim YH. Causes and trends of disabilities in community-dwelling stroke survivors: a population-based study. Brain Neurorehabil 2022;15:e5.
Saini V, Guada L, Yavagal DR. Global epidemiology of stroke and access to acute ischemic stroke interventions. Neurology 2021;97:S6-16.
Kemenkes BKPK. Survei Kesehatan Indonesia Tahun 2023. Jakarta. 2023.
Pu L, Wang L, Zhang R, Zhao T, Jiang Y, et al. Projected global trends in ischemic stroke incidence, deaths and disability-adjusted life years from 2020 to 2030. Stroke 2023;54:1330-1339.
Tiwari A. Neuropsychological evaluation of dementia and depression. Int J Health Sci (Qassim). 2021;5:1015-1020.
Lee KE, Choi M, Jeoung B. Effectiveness of rehabilitation exercise in improving physical function of stroke patients: a systematic review. Int J Environ Res Public Health 2022;19:12739.
De Sousa Fernandes MS, Ordônio TF, Santos GCJ, Santos LER, Calazans CT, Gomes DA, et al. Effects of Physical Exercise on Neuroplasticity and Brain Function: A Systematic Review in Human and Animal Studies. Neural Plast 2020;2020:8856621.
Hamblin MH, Lee JP. Neural stem cells for early intervention of ischemic stroke: Neural stem cell therapy for early phase ischemic stroke. Int J Mol Sci 2021;22:7703.
Subadi I, Sulastri N, Machin A, Hidayati HB, Ramadhan NA. Comparison of the Effects of Wet Cupping Therapy and Exercise on Brain-derived Neurotrophic Factor Expression in Stroke- animal Model. Malaysian J Med Heal Sci 2024;20:124-129.
Ashcroft SK, Ironside DD, Johnson L, Kuys SS, Thompson-Butel AG. Effect of exercise on brain-derived neurotrophic factor in stroke survivors: a systematic review and meta-analysis. Stroke. 2022;53:3706-3716.
Al-Bedah AMN, Elsubai IS, Qureshi NA, Aboushanab TS, Ali GIM, et al. The medical perspective of cupping therapy: Effects and mechanisms of action. J Tradit Complement Med. 2019;9:90-97.
Chirali IZ. Traditional Chinese Medicine Cupping Therapy: Third Edition. Third edit. Traditional Chinese Medicine Cupping Therapy: Third Edition. London: Elsevier Ltd. 2014; pp 1-340.
Heinrich C, Bergami M, Gascón S, Lepier A, Viganò F, et al. Sox2-mediated conversion of NG2 glia into induced neurons in the injured adult cerebral cortex. Stem Cell Rep 2014;3:1000-1014.
Mercurio S, Serra L, Motta A, Gesuita L, Sanchez-Arrones L, et al. Sox2 acts in thalamic neurons to control the development of retina-thalamus-cortex connectivity. iScience. 2019;15:257-273.
Machin A, Divamillenia D, Fatimah N, Susilo I, Purwanto D, et al. The effect of green tea with egcg active compound in enhancing the expression of M2 microglia marker (CD206). Neurol India 2022;70:530-534.
Pekna M, Pekny M, Nilsson M. Modulation of neural plasticity as a basis for stroke rehabilitation. Stroke 2012;43:2819-2828.
Liu C, Wu X, Vulugundam G, Gokulnath P, Li G, et al. Exercise promotes tissue regeneration: mechanisms involved and therapeutic scope. Sport Med Open 2023;9:27.
Han PP, Han Y, Shen XY, Gao ZK, Bi X. Enriched environment-induced neuroplasticity in ischemic stroke and its underlying mechanisms. Front Cell Neurosci 2023;17:1210361.
Qin S, Zhang Z, Zhao Y, Liu J, Qiu J, et al. The impact of acupuncture on neuroplasticity after ischemic stroke: a literature review and perspectives. Front Cell Neurosci 2022;16:817732..
Salaudeen MA, Bello N, Danraka RN, Ammani ML. Understanding the pathophysiology of ischemic stroke: the basis of current therapies and opportunity for new ones. Biomolecules 2024;14:1-23.
Liu W, Wu W, Lin G, Cheng J, Zeng Y, et al. Physical exercise promotes proliferation and differentiation of endogenous neural stem cells via ERK in rats with cerebral infarction. Mol Med Rep 2018;18:1455-1464.
Tsaytler P, Blaess G, Scholze-Wittler M, Koch F, Herrmann BG. Early neural specification of stem cells is mediated by a set of SOX2-dependent neural-associated enhancers. Stem Cell Rep 2024;19:618-628.
Nam SM, Kim JW, Yoo DY, Yim HS, Kim DW, et al. Physical exercise ameliorates the reduction of neural stem cell, cell proliferation and neuroblast differentiation in senescent mice induced by D-galactose. BMC Neurosci 2014;15:1-12.
Wu CW, Chang YT, Yu L, Chen HI, Jen CJ, et al. Exercise enhances the proliferation of neural stem cells and neurite growth and survival of neuronal progenitor cells in dentate gyrus of middle-aged mice. J Appl Physiol 2008;105:1585-1594.
Pansri P, Phanthong P, Suthprasertporn N, Kitiyanant Y, Tubsuwan A, et al. Brain-derived neurotrophic factor increases cell number of neural progenitor cells derived from human induced pluripotent stem cells. PeerJ 2021;9:1-15.
Ludwig PE, Thankam FG, Patil AA, Chamczuk AJ, Agrawal DK. Brain injury and neural stem cells. Neural Regen Res 2018;13:7-18.
| Issue | Vol 10, No 4, 2025 -In Press- | |
| Section | Research Article(s) | |
| Keywords | ||
| Exercise Cupping therapy SOX2 protein Neural stem cells Animal model Ischemic stroke Neuronal plasticity | ||
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