دوره 37، شماره 526: هفته دوم تیر ماه 1398:485-492

تأثیر تمرینات زودهنگام استقامتی بر بهبود ضایعات مغزی در ناحیه‌ی CA1 هیپوکامپ و بیان پروتئین A2A به دنبال سکته‌ی ایسکمیک مغزی در موش صحرایی

مهدی صیدیوسفی , ضیاء فلاح محمدی , مهتاب معظمی , علی یعقوبی , زینب فغفوری

DOI: 10.22122/jims.v37i526.11962

چکیده


مقدمه: ایسکمی/رپرفیوژن مغزی، باعث ایجاد آسیب‌های ساختاری و عملکردی در هیپوکامپ می‌شود. فعالیت فیزیکی، یک روش ضروری و کارآمد در توان‌بخشی زودهنگام پس از سکته‌ی مغزی است. هدف از انجام این مطالعه، بررسی تأثیر ۸ هفته تمرین استقامتی زودهنگام بر روی تردمیل، بر بهبود نورون‌های ناحیه‌ی CA1 هیپوکامپ و بیان پروتئین A2A به دنبال ایسکمی/رپرفیوژن مغزی در موش صحرایی نر بود.

روش‌ها: ۲۱ سر موش صحرایی نر نژاد Wistar به طور تصادفی به سه گروه (Sham، ایسکمی و کنترل و نیز ایسکمی و تمرین) تقسیم شدند. موش‌های گروه ایسکمی و تمرین، ۲۴ ساعت پس از القای ایسکمی به مدت ۸ هفته، ۵ روز در هفته روی نوار گردان دویدند. ایسکمی با انسداد هر دو شریان کاروتید مشترک به مدت ۴۵ دقیقه ایجاد شد. از آزمون Ladder برای بررسی وضعیت عملکردی و از رنگ‌آمیزی هماتوکسیلین- ائوزین (H&E) جهت بررسی میزان مرگ نورونی استفاده گردید. همچنین، جهت بررسی بیان پروتئینی، از روش Immunohistochemistry استفاده شد.

یافته‌ها: ایسکمی مغزی، با افزایش مرگ سلول‌های عصبی ناحیه‌ی CA1 هیپوکامپ و کاهش عملکرد شناختی و یادگیری حرکتی در حیوانات همراه بود. تمرین زودهنگام به طور معنی‌داری باعث کاهش مرگ سلولی و کاهش اختلال شناختی و یادگیری حرکتی شد. همچنین، بیان پروتئین A2A در گروه ایسکمی وتمرین نسبت به گروه ایسکمی + کنترل، تفاوت معنی‌داری نداشت.

نتیجه‌گیری: تمرین زودهنگام روی نوار گردان، به عنوان یک محرک توان‌بخشی، موجب اثرات محافظتی در برابر مرگ سلولی و بهبود عملکرد حرکتی خواهد شد.


واژگان کلیدی


تمرین استقامتی؛ ایسکمی؛ ریپرفیوژن

تمام متن:

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مراجع


Knecht S, Hesse S, Oster P. Rehabilitation after stroke. Dtsch Arztebl Int 2011; 108(36): 600-6.

Antonow-Schlorke I, Ehrhardt J, Knieling M. Modification of the ladder rung walking task-new options for analysis of skilled movements. Stroke Res Treat 2013; 2013: 418627.

Stroke Unit Trialists' Collaboration. Organised inpatient (stroke unit) care for stroke. Cochrane Database Syst Rev 2013; (9): CD000197.

Bernhardt J, Dewey H, Thrift A, Collier J, Donnan G. A very early rehabilitation trial for stroke (AVERT): Phase II safety and feasibility. Stroke 2008; 39(2): 390-6.

Risedal A, Zeng J, Johansson BB. Early training may exacerbate brain damage after focal brain ischemia in the rat. J Cereb Blood Flow Metab 1999; 19(9): 997-1003.

Zhang P, Zhang Q, Pu H, Wu Y, Bai Y, Vosler PS, et al. Very early-initiated physical rehabilitation protects against ischemic brain injury. Front Biosci (Elite Ed) 2012; 4: 2476-89.

Yang YR, Wang RY, Wang PS. Early and late treadmill training after focal brain ischemia in rats. Neurosci Lett 2003; 339(2): 91-4.

Matsuda F, Sakakima H, Yoshida Y. The effects of early exercise on brain damage and recovery after focal cerebral infarction in rats. Acta Physiol (Oxf) 2011; 201(2): 275-87.

Xing Y, Yang SD, Dong F, Wang MM, Feng YS, Zhang F. The beneficial role of early exercise training following stroke and possible mechanisms. Life Sci 2018; 198: 32-7.

Li F, Geng X, Khan H, Pendy JT, Jr., Peng C, Li X, et al. Exacerbation of brain injury by post-stroke exercise is contingent upon exercise initiation timing. Front Cell Neurosci 2017; 11: 311.

Shen J, Huber M, Zhao EY, Peng C, Li F, Li X, et al. Early rehabilitation aggravates brain damage after stroke via enhanced activation of nicotinamide adenine dinucleotide phosphate oxidase (NOX). Brain Res 2016; 1648(Pt A): 266-76.

Diserens K, Michel P, Bogousslavsky J. Early mobilisation after stroke: Review of the literature. Cerebrovasc Dis 2006; 22(2-3): 183-90.

Williams-Karnesky RL, Stenzel-Poore MP. Adenosine and stroke: Maximizing the therapeutic potential of adenosine as a prophylactic and acute neuroprotectant. Curr Neuropharmacol 2009; 7(3): 217-27.

Desai A, Victor-Vega C, Gadangi S, Montesinos MC, Chu CC, Cronstein BN. Adenosine A2A receptor stimulation increases angiogenesis by down-regulating production of the antiangiogenic matrix protein thrombospondin 1. Mol Pharmacol 2005; 67(5): 1406-13.

Gracia E, Farre D, Cortes A, Ferrer-Costa C, Orozco M, Mallol J, et al. The catalytic site structural gate of adenosine deaminase allosterically modulates ligand binding to adenosine receptors. FASEB J 2013; 27(3): 1048-61.

Mazzon E, Esposito E, Impellizzeri D, DI PR, Melani A, Bramanti P, et al. CGS 21680, an agonist of the adenosine (A2A) receptor, reduces progression of murine type II collagen-induced arthritis. J Rheumatol 2011; 38(10): 2119-29.

Borea PA, Gessi S, Merighi S, Vincenzi F, Varani K. Pharmacology of adenosine receptors: The state of the art. Physiol Rev 2018; 98(3): 1591-625.

Sharifi ZN, Abolhassani F, Hassanzadeh G, Zarrindast MR, Movassaghi S. Neuroprotective treatment with FK506 reduces hippocampal damage and prevents learning and memory deficits after transient global ischemia in rat. Arch Neurol 2014; 1(1): 35-40.

Erfani S, Khaksari M, Oryan S, Shamsaei N, Aboutaleb N, Nikbakht F. Nampt/PBEF/visfatin exerts neuroprotective effects against ischemia/reperfusion injury via modulation of Bax/Bcl-2 ratio and prevention of caspase-3 activation. J Mol Neurosci 2015; 56(1): 237-43.

Bedford TG, Tipton CM, Wilson NC, Oppliger RA, Gisolfi CV. Maximum oxygen consumption of rats and its changes with various experimental procedures. J Appl Physiol Respir Environ Exerc Physiol 1979; 47(6): 1278-83.

Wallace DG, Winter SS, Metz GA. Serial pattern learning during skilled walking. J Integr Neurosci 2012; 11(1): 17-32.

Hofman FM, Taylor CR. Immunohistochemistry. Curr Protoc Immunol 2013; 103(1): 21.

Bonde C, Noraberg J, Noer H, Zimmer J. Ionotropic glutamate receptors and glutamate transporters are involved in necrotic neuronal cell death induced by oxygen-glucose deprivation of hippocampal slice cultures. Neuroscience 2005; 136(3): 779-94.

Sattler R, Tymianski M. Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death. Mol Neurobiol 2001; 24(1-3): 107-29.

Endres M, Dirnagl U, Moskowitz MA. The ischemic cascade and mediators of ischemic injury. Handb Clin Neurol 2009; 92: 31-41.

Kima GY, Kimb EJ. The effect of physical training on glutamate transporter expression in an experimental ischemic stroke rat model. Phys Ther Rehabil Sci 2013; 2(2): 87-91.

Sosa PM, Schimidt HL, Altermann C, Vieira AS, Cibin FW, Carpes FP, et al. Physical exercise prevents motor disorders and striatal oxidative imbalance after cerebral ischemia-reperfusion. Braz J Med Biol Res 2015; 48(9): 798-804.

Stout JM, Knapp AN, Banz WJ, Wallace DG, Cheatwood JL. Subcutaneous daidzein administration enhances recovery of skilled ladder rung walking performance following stroke in rats. Behav Brain Res 2013; 256: 428-31.

Morris RG, Garrud P, Rawlins JN, O'Keefe J. Place navigation impaired in rats with hippocampal lesions. Nature 1982; 297(5868): 681-3.

Liu YF, Chen HI, Wu CL, Kuo YM, Yu L, Huang AM, et al. Differential effects of treadmill running and wheel running on spatial or aversive learning and memory: Roles of amygdalar brain-derived neurotrophic factor and synaptotagmin I. J Physiol 2009; 587(Pt 13): 3221-31.

Teixeira AL, Barbosa IG, Diniz BS, Kummer A. Circulating levels of brain-derived neurotrophic factor: Correlation with mood, cognition and motor function. Biomark Med 2010; 4(6): 871-87.

Suzuki J. Muscle microvascular adaptation and angiogenic gene induction in response to exercise training are attenuated in middle-aged rats. Comparative Exercise Physiology: 2015; 11(1): 23-33.

Hayashi T, Noshita N, Sugawara T, Chan PH. Temporal profile of angiogenesis and expression of related genes in the brain after ischemia. J Cereb Blood Flow Metab 2003; 23(2): 166-80.

Chen Z, Hu Q, Xie Q, Wu S, Pang Q, Liu M, et al. Effects of treadmill exercise on motor and cognitive function recovery of MCAO mice through the caveolin-1/vegf signaling pathway in ischemic penumbra. Neurochem Res 2019; 44(4): 930-46.

Baxter RL, Vega-Riveroll LJ, Deuchars J, Parson SH. A2A adenosine receptors are located on presynaptic motor nerve terminals in the mouse. Synapse 2005; 57(4): 229-34.

Mojsilovic-Petrovic J, Jeong GB, Crocker A, Arneja A, David S, Russell DS, et al. Protecting motor neurons from toxic insult by antagonism of adenosine A2a and Trk receptors. J Neurosci 2006; 26(36): 9250-63.

Fontinha BM, Diogenes MJ, Ribeiro JA, Sebastiao AM. Enhancement of long-term potentiation by brain-derived neurotrophic factor requires adenosine A2A receptor activation by endogenous adenosine. Neuropharmacology 2008; 54(6): 924-33.

Ramanathan M, Pinhal-Enfield G, Hao I, Leibovich SJ. Synergistic up-regulation of vascular endothelial growth factor (VEGF) expression in macrophages by adenosine A2A receptor agonists and endotoxin involves transcriptional regulation via the hypoxia response element in the VEGF promoter. Mol Biol Cell 2007; 18(1): 14-23.

Fontinha BM, Delgado-Garcia JM, Madronal N, Ribeiro JA, Sebastiao AM, Gruart A. Adenosine A(2A) receptor modulation of hippocampal CA3-CA1 synapse plasticity during associative learning in behaving mice. Neuropsychopharmacology 2009; 34(7): 1865-74.

Correia-de-Sa P, Sebastiao AM, Ribeiro JA. Inhibitory and excitatory effects of adenosine receptor agonists on evoked transmitter release from phrenic nerve ending of the rat. Br J Pharmacol 1991; 103(2): 1614-20.

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. J Neuroeng Rehabil 2013; 10: 43.

Sharma HS, Westman J, Nyberg F. Pathophysiology of brain edema and cell changes following hyperthermic brain injury. Prog Brain Res 1998; 115: 351-412.

Marmarou A. The pathophysiology of brain edema and elevated intracranial pressure. Cleve Clin J Med 2004; 71(Suppl 1): S6-S8.

Tian S, Zhang Y, Tian S, Yang X, Yu K, Zhang Y, et al. Early exercise training improves ischemic outcome in rats by cerebral hemodynamics. Brain Res 2013; 1533: 114-21.

Zhang P, Xianglei J, Hongbo Y, Zhang J, Xu C. Neuroprotection of Early locomotor exercise poststroke: evidence from animal studies. Can J Neurol Sci 2015; 42(4): 213-20.

Sun J, Tong RK-Y, Ke I, Zhang J, Hu X, Zheng X. Treadmill exercise facilitates functional recovery and neuroprotection in subacute stroke rat. Int J Biosci Biochem Bioinforma 2013; 3(2): 170-3.

McEwen BS. Stress and hippocampal plasticity. Annu Rev Neurosci 1999; 22: 105-22.




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