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Neuroprotective Effect of the Combination of Aerobic Exercise and Adenosine on the A2A Receptor Gene Expression and Complications of Cerebral Stroke in the Hippocampus of adult Male Rat

Document Type : Research Paper

Authors

1 Department of Exercise Physiology, Faculty of Sport Sciences, Ferdowsi University of Mashhad.Mashhad. Iran

2 Associate Professorof Department of Exercise Physiology, Faculty of Sport Sciences, Ferdowsi University of Mashhad,, Mashhad, Iran.

3 Professor of Department of Sports Physiology, Faculty of physical education and sport sciences, Ferdowsi University of Mashhad, Mashhad, Iran

4 professor of department of exercise physiology. faculty of sport sciences. ferdowsi university of mashhad. mashhhad. iran

Abstract

Objectives: Stroke is a neurological disorder and the second leading cause of death worldwide. Recently, studies on neuroprotective treatments for stroke have become a hot topic globally. The present study aimed to investigate the neuroprotective effect of a combination of aerobic exercise and adenosine on the expression of the A2a gene and the consequences of stroke injury in the hippocampus of male rats. Materials and Methods: Fifty male Wistar rats (8-10 weeks old, weighing 240-270 grams) were randomly divided into five groups: (sham, control+ischemia, ischemia+exercise, ischemia+adenosine, and ischemia+adenosine+exercise). After inducing ischemia, rats in exercise groups performed treadmill running 5 days per week for 8 week. Adenosine simultaneously once per day to Adenosine-treated groups were injected. 48 hours after completing the exercise protocol, hippocampal tissue was collected for cell death, and measuring of the A2a expression using the RT- PCR method. The data were analyzed using Anova and post hoc Bonferroni’s test. Results: The number of dead cells increased in the ischemia group compared to the sham and decreased in the ischemia+adenosine+Exercise and ischemia+exercise groups compared to the ischemia group. The A2a expression in group ischemia+adenosine+exercise, ischemia+exercise, and ischemia+adenosine showed respectively the highest increase, with a significant difference compared to the sham (P<0/001) and control+ischemia (P<0/001) groups. Conclusion: aerobic exercise and adenosine, both independently and interactively, can serve as a neuroprotective combination by increasing the expression of the A2a and stimulating the signaling and mechanisms related to the reduction of cell death, providing therapeutic and protective effects against ischemic stroke-induced consequences.

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References
  1. Andrea V, and Emanuela M. State of the art and future of stem cell therapy in ischemic stroke: why don’t we focus on their administration? Bioengineering. 2023;10(1):118
  2. Shan Y, Wang L, Sun J, Chang Sh, Wei D, Lv H. Exercise preconditioning attenuates cerebral ischemia-induced neuronal apoptosis, Th17/Treg imbalance, and inflammation in rats by inhibiting the JAK2/STAT3 pathway. Brain and Behavior. 2023;13(6):e3030.
  3. Qin Ch, Yang Sh, Cho Y-H, Zhang H, Pang X-W, Chen L, et al. Signaling pathways involved in ischemic stroke: molecular mechanisms and therapeutic interventions. Signal Transduction and Targeted Therapy. 2022;7:215.
  4. Mollet I, Marto JP, Mendonça M, Baptista MV, Vieira Helena LA. Remote but not distant: a review on experimental models and clinical trials in remote ischemic conditioning as potential therapy in ischemic stroke. Molecular Neurobiology. 2022;59(1):294–325.
  5. Campbell BCV, De Silva DA, Macleod MR, Coutts SB, Schwa mm LH, Davis SM, et al. Ischemic stroke. Nat Rev Dis Primers. 2019;5(1):70.
  6. Zhang H, Lee JY, Borlongan CV, Tajiri N. A brief physical activity protects against ischemic stroke. Brain Circ. 2019;5(3):112-8.
  7. Caplan LR. Transient ischemic attack: definition and natural history. Current Atherosclerosis Reports. 2006;(8)4:276-80.
  8. Zhang H, Xie Q, Hu J. Neuroprotective effect of physical activity in ischemic stroke: focus on the neurovascular unit. Front Cell Neurosci. 2022;16:860573.
  9. Maleki M, Hatami Nemati H, Ahmadi H, Nasri S. The effect of short- and long-term exercise courses on memory impairment induced by ethidium bromide injection in the hippocampus of the brain of male rats. Sport Physiology. 2022;14(55):71-94. (In Persian).
  10. Liebelt B, Papapetrou P, Ali A, Guo M, Ji X, Peng C, et al. Exercise preconditioning reduces neuronal apoptosis in stroke by up-regulating heat shock protein-70 (heat shock protein-72) and extracellular-signal-regulated kinase 1/2. 2010;14;166(4):1091-100.
  11. Yang X, He Z, Zhang Q, Wu Y, Hu Y, Wang X, et al. Pre-isch­emic treadmill training for prevention of ischemic brain inju­ry via regulation of glutamate and its transporter GLT-1. Int J Mol Sci. 2012;13(8):9447-59.
  12. Wang YL, Lin CH, Chen CC, Chang CP, Lin KC, Su FC, et al. Exercise preconditioning attenuates neurological injury by preserving old and newly formed HSP72-containing neurons in focal brain ischemia rats. Int J Med Sci. 2019;16(5):675-85.
  13. Gill SS, Rochon PA, Herrmann N, Lee PE, Sykora K, Gunraj N, et al. Atypical antipsychotic drugs and risk of ischemic stroke: population based retrospective cohort study. BMJ. 2005;330:7489445.
  14. Maulaz AB, Bezerra DC, Michael P, Bogousslavsky J. Effect of discontinuing aspirin therapy on the risk of brain ischemic stroke. Archives of N 2005;62(8):1217-20.
  15. Daniele SG, Trummer G, Hossmann KA, Vrselja Z, Benk C, Gobeske KT, et al. Brain vulnerability and viability after ischaemia. Nat Rev Neurosci. 2021;22:553–72.
  16. Ådén U, Haldner L, Lagercrantz H, Dalmau I, Ledent C, Fredholm BB. Aggravated brain damage after hypoxic ischemia in immature adenosine A2A knockout mice. Stroke. 2003;34(3):739-44.
  17. Assaife-Lopes N, Sousa VC, Pereira DB, Ribeiro JA, Chao MV, and Sebastião AM Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts: implications for neuromodulation. Journal of Neuroscience. 2010;30(25):8468-80.
  18. Hasko G, Pacher P, Vizi ES, Illes P. Adenosine receptor signaling in the brain immune system. Trends Pharmacol Sci. 2005;26(10):511-16.
  19. Aymerich I, Foufelle F, Ferre P, Casado F, Pastor M. Extracellular adenosine activates AMPdependent protein kinase (AMPK). J Cell Sci. 2006;119(Pt 8):1612-21.
  20. Wardas J. Neuroprotective role of adenosine_in the CNS. J Pharmacol. 2002;54(4): 313-26.
  21. KO I-G, Jin J-J, Hwang L, Kim S-H, Kim C-J, Jeon JW, et al. Adenosine A2A receptor agonist polydeoxyribonucleotide ameliorates short-term memory impairment by suppressing cerebral ischemia-induced inflammation via MAPK pathway. PLoS ONE. 2021;16(3):e0248689.
  22. Colgan SP, HK Eltzschig. Adenosine and hypoxiainducible factor signaling in intestinal injury and recovery. Annu Rev Physiol. 2012;74:153-75.
  23. Duflot S, Riera B, Fernández- Veledo S, Casadó V, Norman RI, Casado FJ, et al. ATP-sensitive K(+) channels regulate the concentrative adenosine transporter CNT2 following activation by A(1) adenosine receptors. Mol Cell Biol. 2004;24(7):2710-9.
  24. Brian J K. Adenosine A2a receptors and O (2) sensing in development. Am J Physiol Regul Integr Comp Physiol. 2011;301(3):R601-R22.
  25. Popoli Patrizia and Rita Pepponi. Potential. Therapeutic relevance of adenosine A2B and A2A receptors in the central nervous system. CNS & Neurological Disorder. 2012;11(6):664-74.
  26. Fredholm BB. Adenosine, an endogenous distress signal, modulates tissue damage and repair.  Cell Death & Differentiation. 2007;14(7):1315-23.
  27. Bansal S, Sangha KS, Khatri P. Drug treatment of acute ischemic stroke. Am J Cardiovasc drugs. 2013;13(1):57–69.
  28. Leandr CG, Levada AC, Hirabara SM, Manhães-d Castro R, et al. A program of moderate physical training fo rats based on maximal oxygen consumption. Journal of Stren. 2007;21(3):751-6.
  29. Liu J, Gu Y, Guo M, & Ji X. Neuroprotective effects and mechanisms of ischemic/hypoxic preconditioning on neurological diseases. CNS Neuroscience & Ther. 2021;27(8):869–82.
  30. Gertz K, Priller J, Kronenberg G, Fink KB, Winter B, Schröck H, Shengbo Ji, et al. Physical activity improves long-term stroke outcome via endothelial nitric oxide synthase–dependent augmentation of neovascularization and cerebral blood flow. Circulation ResearchVolume. 2006;99(10):1132-40.
  31. Mizutani K, Sonoda S, Yamada K, Beppu H, Shimpo K. Alteration of protein expression profile following voluntary exercise in the perilesional cortex of rats with focal cerebral infarction. Brain Res. 2011;14(16):61-
  32. Zhang Q, Zhang L, Yang X, Wan Y, Jia J. The effects of exer­cise preconditioning on cerebral blood flow change and en­dothelin-1 expression after cerebral ischemia in rats. J Stroke Cerebrovascular Dis. 2014;23:1696-702.
  33. Carrol TJ, Barry B, Riek S, Carson RG. Resistance training enhances the stability of sensorimotor coordination. Proc Biol Sci .2001;268(1464):221-7.
  34. Quaney BM, Boyd LA, McDowd JM, Zahner LH, He J, Mayo MS, et al. Aerobic exercise improves cognition and motor function post stroke. Nauru rehabilitat. 2009;23(9):879-85.
  35. Svensson M, Rosvall P, Boza-Serrano A, Andersson E, Lexell J, Deierborg T. Forced treadmill exercise can induce s tress and increase neuronal damage in a mouse model of global cerebral ischemia. Neurobiology of Stress. 2016;5:8-18.
  36. Fang JS, Gillies RD, Gatenby RA, Adaptation to hypoxia and acidosis in carcinogenes­­is and tumor progression. Semin Cancer Biol. 2008; 18(5):330-7.
  37. Hardie DG, Scott JW, Pan DA, Hudson ER. Management of Cellular Energy by the AMP Activated Protein Kinase System. FEBS Lett. 2003;546(1):113–20.
  38. Vanessa S. Peroxisome proliferator-activated receptors as targets to treat non-alcoholic fatty liver disease.World J Hepatol. 2015;7(8):1012–9.
  39. Hart ML, Hypoxia-inducible factor-1alpha-dependent protection from intestinal ischemia/reperfusion injury involves ecto-5'-nucleotidas (CD73) and the A2B adenosine receptor. J Immunol. 2011;186(10): 4367-74.
  40. Le Y-Z, Xu B, Chucair-Elliott AJ, Zhang H, and Zhu M. VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes. Biomolecules. 2021;11(5):712.
  41. Oyamada N, Itoh H, Sone M, Yamahara K, Miyashita K, Park K, et al. Transplantation of vascular cells derived from human embryonic stem cells contributes to vascular regeneration after s troke in mice. Journal of Translational Medicine. 2008;6(1): 54.
  42. Viboolvorakul S, Patumraj S. Exercise Training could improve age-related changes in cerebral blood flow and capillary vascularity through the upregulation of vegf and enos. Biomed Res International. 2014;2014;230791.
  43. Natasha T L, Lin K O, Prajwal G, Che Mohd N, Muzaimi M, Harshal H. Nandurkar et AL. Role of purinergic signalling in endothelial dysfunction and thrombo-inflammation in ischemic stroke and cerebral small vessel disease. Biomolecules. 2021;11(7):
  44. Garcia GE, Truong LD, Li P, Zhang P, Du J, Chen J-F et al. Adenosine A2A receptor activation and macrophage-mediated experimental glomerulonephritis. The FASEB Journal.2008;22(2):445-54.
  45. Zhang P, Yu H, Zhou N, Zhang J, Wu Y, Zhang Y, et al. Early exercise improves cerebral blood flow through increased angiogenesis in experimental stroke rat model. Journal of neuroengi, 2013;10(1):43.
  46. Feng R, Zhang M, Wang X, Li WB, Ren SQ, and Zhang F. Pre-isch­emic exercise alleviates oxidative damage following ischemic stroke in rats. Exp Ther Med. 2014;8(4):1325-9.
  47. Zhao ZQ, Budde JM, Morris C, Wang NP, Velez DA, Muraki S, et al. Adenosine attenuates reperfusion-induced apoptotic cell death by modulating expression of Bcl-2 and Bax proteins. J Mol Cell Cardiol. 2001;33(1):57-68.
Sport Physiology
Volume 15, Issue 58
July 2023
Pages 125-148
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History
  • Receive Date: 03 September 2023
  • Revise Date: 07 October 2023
  • Accept Date: 02 December 2023
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