Volume 10, Issue 1 (January & February 2019)                   BCN 2019, 10(1): 73-84 | Back to browse issues page

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Akhoundzadeh K, Vakili A, Sameni H R. Bone Marrow Stromal Cells With Exercise and Thyroid Hormone Effect on Post-Stroke Injuries in Middle-aged Mice. BCN 2019; 10 (1) :73-84
URL: http://bcn.iums.ac.ir/article-1-1105-en.html
Bone Marrow Stromal Cells With Exercise and Thyroid Hormone Effect on Post-Stroke Injuries in Middle-aged Mice
Kobra Akhoundzadeh1 , Abedin Vakili * 1, Hamid Reza Sameni2
1- Physiology Research Center, Semnan University of Medical Sciences, Semnan, Iran.
2- Nervous System Stems Cells Research Center, Department of Anatomical Sciences, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
Abstract:  
Introduction: Based on our previous findings, the treatment of stem cells alone or in combination with thyroid hormone (T3) and mild exercise could effectively reduce the risk of stroke damage in young mice. However, it is unclear whether this treatment is effective in aged or middle-aged mice. Therefore, this study designed to assess whether combination of Bone Marrow Stromal Cells (BMSCs) with T3 and mild treadmill exercise can decrease stroke complications in middle-aged mice. 
Methods: Under laser Doppler flowmetry monitoring, transient focal cerebral ischemia was produced by right Middle Cerebral Artery Occlusion (MCAO) for 45 min followed by 7 days of reperfusion in middle-aged mice. BMSCs (1×105) were injected into the right cerebral ventricle 24 h after MCAO, followed by daily injection of triiodothyronine (T3) (20 µg/100 g/d SC) and 6 days of running on a treadmill. Infarct size, neurological function, apoptotic cells and expression levels of Glial Fibrillary Acidic Protein (GFAP) were evaluated 1 week after stroke.
Results: Post-ischemic treatment with BMSCs or with T3 and or mild treadmill exercise alone or in combination did not significantly change neurological function, infarct size, and apoptotic cells 7 days after ischemia in middle-aged mice (P>0.05). However, the expression of GFAP significantly reduced after treatment with BMSCs and or T3 (P<0.01).  
Conclusion: Our findings indicate that post-stroke treatment BMSCs with exercise and thyroid hormone cannot reverse neuronal damage 7 days after ischemia  in middle-aged mice. These findings further support that age is an important variable in stroke treatment
Keywords: Cerebral ischemia, Combination, Bone marrow stromal cells, Thyroid hormone, Exercise, Apoptosis, Glial fibrillary acidic protein, Middle-aged, Mice
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Type of Study: Original | Subject: Cellular and molecular Neuroscience
Received: 2018/01/6 | Accepted: 2018/06/12 | Published: 2019/01/1
References
1. Abbaszadeh, H. A., Tiraihi, T., Delshad, A. R., Zadeh, M. S., & Taheri, T. (2013). Bone marrow stromal cell transdifferentiation into oligodendrocyte-like cells using triiodothyronine as a inducer with expression of platelet-derived growth factor α as a maturity marker. Iranian Biomedical Journal, 17(2), 62-7. [PMID] [PMCID] [PMID] [PMCID]
2. Akhoundzadeh, K., Vakili, A., Sameni, H. R., Vafaei, A. A., Rashidy-Pour, A., Safari, M., et al. (2017). Effects of the combined treatment of bone marrow stromal cells with mild exercise and thyroid hormone on brain damage and apoptosis in a mouse focal cerebral ischemia model. Metabolic Brain Disease, 32(4), 1267-77. [DOI:10.1007/s11011-017-0034-0] [DOI:10.1007/s11011-017-0034-0]
3. Alevizaki, M., Synetou, M., Xynos, M., Pappa, T., & Vemmos, K. N. (2007). Low triiodothyronine: A strong predictor of outcome in acute stroke patients. European Journal of Clinical Investigation, 37(2), 651–7. [DOI:10.1111/j.1365-2362.2007.01839.x] [PMID] [DOI:10.1111/j.1365-2362.2007.01839.x]
4. Ambrogini, P., Cuppini, R., Ferri, P., Mancini, C., Ciaroni, S., Voci, A., et al. (2005). Thyroid hormones affect neurogenesis in the dentate gyrus of adult rat. Neuroendocrinology, 81(4), 244-53. [DOI:10.1159/000087648] [PMID] [DOI:10.1159/000087648]
5. Arsava, E., Vural, A., Akpinar, E., Gocmen, R., Akcalar, S., Oguz, K., et al. (2013). The detrimental effect of aging on leptomeningeal collaterals in ischemic stroke. Journal of Stroke & Cerebrovascular Disease, 23(3), 421-6. [DOI:10.1016/j.jstrokecerebrovasdis.2013.03.014] [PMID]
6. Badan, I., Buchhold, B., Hamm, A., Gratz, M., Walker, L. C., Platt, D., et al. (2003). Accelerated glial reactivity to stroke in aged rats correlates with reduced functional recovery. Journal of Cerebral Blood Flow & Metabolism, 23(3), 845–54. [DOI:10.1097/01.WCB.0000071883.63724.A7] [PMID] [DOI:10.1097/01.WCB.0000071883.63724.A7]
7. Balseanu, A., Buga, A., & Popa-Wagner, A. (2010). Cellular response to cerebral ischemia during aging. Current Science, 35(4), 209-18.
8. Bang, O. Y., Lee, J. S., Lee, P. H., & Lee, G. (2005). Autologous mesenchymal stem cell transplantation in stroke patients. Annals of Neurology, 57(6), 874-82. [DOI:10.1002/ana.20501] [PMID] [DOI:10.1002/ana.20501]
9. Bejot, Y., Rouaud, O., Jacquin, A., Osseby, G. V., Durier, J., Manckoundia, P., et al. (2010). Stroke in the very old: Incidence, risk factors, clinical features, outcomes and access to resources—A 22-year population-based study. Cerebrovascular Disease, 29(2), 111-21. [DOI:10.1159/000262306] [PMID] [DOI:10.1159/000262306]
10. Benvenuti, S., Luciani, P., Cellai, I., Deledda, C., Baglioni, S., Saccardi, R., et al. (2008). Thyroid hormones promote cell differentiation and up-regulate the expression of the seladin-1 gene in in vitro models of human neuronal precursors. Journal of Endocrinology, 197(2), 437-46. [DOI:10.1677/JOE-07-0324] [PMID] [DOI:10.1677/JOE-07-0324]
11. Bunevicius, A., Iervasi, G., & Bunevicius, R. (2015). Neuroprotective actions of thyroid hormones and low-T3 syndrome as a biomarker in acute cerebrovascular disorders. Expert Reviewi of Neurotherapy, 15(3), 315-26. [DOI:10.1586/14737175.2015.1013465] [PMID] [DOI:10.1586/14737175.2015.1013465]
12. Carter, R. (1999). Characterization of progressive motor deficits in mice transgenic for the human Huntington's disease mutation. Journal of Neuroscience, 19(4), 3248-57. [DOI:10.1523/JNEUROSCI.19-08-03248.1999] [PMID] [DOI:10.1523/JNEUROSCI.19-08-03248.1999]
13. Chen, J., Li, Y., Wang, L., Lu, M., Zhang, X., & Chopp, M. (2001). Therapeutic benefit of intracerebral transplantation of bone marrow stromal cells after cerebral ischemia in rats. Journal of the Neurological Sciences, 189(1), 49-57. [DOI:10.1016/S0022-510X(01)00557-3] [DOI:10.1016/S0022-510X(01)00557-3]
14. Darsalia, V., Heldmann, U., Lindvall, O., & Kokaia, Z. (2005). Stroke-induced neurogenesis in aged brain. Stroke, 36(1), 1790-5. [DOI:10.1161/01.STR.0000173151.36031.be] [PMID] [DOI:10.1161/01.STR.0000173151.36031.be]
15. Diez, D., Grijota-Martinez, C., Agretti, P., De Marco, G., Tonacchera, M., Pinchera, A., et al. (2008). Thyroid hormone action in the adult brain: gene expression profiling of the effects of single and multiple doses of triiodo-L-thyronine in the rat striatum. Endocrinology, 149(8), 3989-4000. [DOI:10.1210/en.2008-0350] [PMID] [DOI:10.1210/en.2008-0350]
16. Dubska, L. E., Matalova, I., & Misek, I. (2002). Detection of apoptosis in paraffin embedded tissues: the influence of tissue type and fixation. Acta Veterina, 71(1), 529-33. [DOI:10.2754/avb200271040529] [DOI:10.2754/avb200271040529]
17. Eady, T. N., Khoutorova, L., Obenaus, A., Mohd-Yusof, A., Bazan, N. G., & Belayev, L. (2014). Docosahexaenoic acid complexed to albumin provides neuroprotection after experimental stroke in aged rats. Neurobiology Disesea, 62(1), 1-17. [DOI:10.1016/j.nbd.2013.09.008] [PMID] [PMCID] [DOI:10.1016/j.nbd.2013.09.008]
18. Gao, Y., Zhao, Y., Pan, J., Yang, L., Huang, T., Feng, X., et al. (2014). Treadmill exercise promotes angiogenesis in the ischemic penumbra of rat brains through caveolin-1/VEGF signaling pathways. Brain Research, 1585, 83–90. [DOI:10.1016/j.brainres.2014.08.032] [DOI:10.1016/j.brainres.2014.08.032]
19. Hicks, A. U., Hewlett, K., Windle, V., Chernenko, G., Ploughman, M., Jolkkonen, J., et al. (2007). Enriched environment enhances transplanted subventricular zone stem cell migration and functional recovery after stroke. Neuroscience, 146(1), 31-40. [DOI:10.1016/j.neuroscience.2007.01.020] [DOI:10.1016/j.neuroscience.2007.01.020]
20. Hiona, A., & Leeuwenburgh, C. (2004). Effects of age and caloric restriction on brain neuronal cell death/survival. Annual New York Academy of Science, 1019, 96-105. [DOI:10.1196/annals.1297.018] [PMID] [DOI:10.1196/annals.1297.018]
21. Ikeda, N., Nonoguchi, N., Zhao, M., Watanabe, T., Kajimoto, Y., Furutama, D., et al. (2005). Bone marrow stromal cells that enhanced fibroblast growth factor-2 secretion by herpes simplex virus vector improve neurological outcome after transient focal cerebral ischemia in rats. Stroke, 36(4), 2725-30. [DOI:10.1161/01.STR.0000190006.88896.d3] [PMID] [DOI:10.1161/01.STR.0000190006.88896.d3]
22. Jin, K., Mao, X., Xie, L., Greenberg, R. B., Peng, B., Moore, A., et al. (2010). Delayed transplantation of human neural precursor cells improves outcome from focal cerebral ischemia in aged rats. Aging Cell, 9(6), 1076–83. [DOI:10.1111/j.1474-9726.2010.00638.x] [PMID] [PMCID] [DOI:10.1111/j.1474-9726.2010.00638.x]
23. Kelly, K., Li, X., Tan, Z., VanGilder, R., Rosen, C., & Huber, J. (2009). NOX2 inhibition with apocynin worsens stroke outcome in aged rats. Brain Research, 6(1292), 165-72. [DOI:10.1016/j.brainres.2009.07.052] [PMID] [PMCID] [DOI:10.1016/j.brainres.2009.07.052]
24. Leasure, J. L., & Grider, M. (2010). The effect of mild post-stroke exercise on reactive neurogenesis and recovery of somatosensation in aged rats. Experimental Neurology, 226(13), 58-67. [DOI:10.1016/j.expneurol.2010.08.003] [DOI:10.1016/j.expneurol.2010.08.003]
25. Lee, D. H., Lee, J. Y., Oh, B. M., Phi, J. H., Kim, S. K., Bang, M. S., et al. (2013). Functional recovery after injury of motor cortex in rats: Effects of rehabilitation and stem cell transplantation in a traumatic brain injury model of cortical resection. Childs Nerve System, 29(4), 403-11. [DOI:10.1007/s00381-012-1969-4] [DOI:10.1007/s00381-012-1969-4]
26. Leu, S., Lin, Y. C., Yuen, C. M., Yen, C. H., Kao, Y. H., Sun, C. K., et al. (2010). Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats. Journal of Translational Medicine, 8(63), 1-16. [DOI:10.1186/1479-5876-8-63] [DOI:10.1186/1479-5876-8-63]
27. Li, S., Zheng, J., & Carmichael, S. T. (2005). Increased oxidative protein and DNA damage but decreased stress response in the aged brain following experimental stroke. Neurobiology of Disease, 18(3), 432–40. [DOI:10.1016/j.nbd.2004.12.014] [PMID] [DOI:10.1016/j.nbd.2004.12.014]
28. Li, Y., Chopp, M., Chen, J., Wang, L., Gautam, S. C., Xu, Y. X., et al. (2000). Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. Journal of Cerebral Blood Flow & Metabolism, 20(9), 1311-9. [DOI:10.1097/00004647-200009000-00006] [PMID] [DOI:10.1097/00004647-200009000-00006]
29. Ma, Y., Qiang, L., & He, M. (2013). Exercise therapy augments the ischemia-induced proangiogenic state and results in sustained improvement after stroke. International Journal of Molecular Sciences, 14(4), 8570-84. [DOI:10.3390/ijms14048570] [DOI:10.3390/ijms14048570]
30. Marini, C., Triggiani, L., Cimini, N., Ciancarelli, I., De Santis, F., Russo, T., & Baldassarre, M. (2001). Proportion of older people in the community as a predictor of increasing stroke incidence. Neuroepidemiology, 20(2), 91-5. [DOI:10.1159/000054766] [PMID] [DOI:10.1159/000054766]
31. O'Keefe, L. M., Conway, S. E., Czap, A., Malchoff, C. D., Benashski, S., Fortunato, G., et al. (2015). Thyroid hormones and functional outcomes after ischemic stroke. Thyroid Research, 8(9), 2-5. [DOI:10.1186/s13044-015-0021-7]
32. Panahpour, H., Dehghani, G. A., & Bohlooli, S. (2014). Enalapril attenuates ischaemic brain oedema and protects the blood–brain barrier in rats via an anti-oxidant action. Clinical and Experimental Pharmacology and Physiology, 41(3), 220-6. [DOI:10.1111/1440-1681.12210] [PMID] [DOI:10.1111/1440-1681.12210]
33. Paxinos, G., & Franklin, K. B. J. (2001). The mouse brain in stereotaxic coordinates. 2nd Ed. Amsterdam: Elsevier.
34. Popa-Wagner, A., Badan, I., Walker, L., Groppa, S., Patrana, N., & Kessler, C. (2007). Accelerated infarct development, cytogenesis and apoptosis following transient cerebral ischemia in aged rats. Acta Neuropathology, 113(3), 277-93. [DOI:10.1007/s00401-006-0164-7] [PMID] [DOI:10.1007/s00401-006-0164-7]
35. Popa-Wagner, A., Buga, A. M., Tica, A. A., & Albu, C. V. (2014). Perfusion deficits, inflammation and aging precipitate depressive behaviour. Biogerontology, 15(5), 439–48. [DOI:10.1007/s10522-014-9516-1] [PMID] [DOI:10.1007/s10522-014-9516-1]
36. Popa-Wagner, A., Filfan, M., Uzoni, A., Pourgolafshan, P., & Buga, A. M. (2015). Poststroke cell therapy of the aged brain. Hindawi Publishing Corporation: Neural Plasticity, 2015, 7-31. [DOI:10.1155/2015/839638] [PMID] [PMCID] [DOI:10.1155/2015/839638]
37. Rehni, A. K., Singh, N., Jaggi, A. S., & Singh, M. (2007). Amniotic fluid derived stem cells ameliorate focal cerebral ischaemia-reperfusion injury induced behavioural deficits in mice. Behavioural Brain Research, 183, 95-100. [DOI:10.1016/j.bbr.2007.05.028] [DOI:10.1016/j.bbr.2007.05.028]
38. Seo, T. B., Kim, T. W., Shin, M. S., Ji, E. S., Cho, H. S., Lee, J. M., et al. (2014). Aerobic exercise alleviates ischemia-induced memory impairment by enhancing cell proliferation and suppressing neuronal apoptosis in hippocampus. International Neurourology Journal, 18(3), 187-97. [DOI:10.5213/inj.2014.18.4.187] [PMID] [PMCID] [DOI:10.5213/inj.2014.18.4.187]
39. Shen, L. H., Li, Y., Chen, J., Zhang, J., Vanguri, P., Borneman, J., et al. (2006). Intracarotid transplantation of bone marrow stromal cells increases axon-myelin remodeling after stroke. Neuroscience, 137(2), 393-9. [DOI:10.1016/j.neuroscience.2005.08.092] [PMID] [DOI:10.1016/j.neuroscience.2005.08.092]
40. Simonides, W. S., Mulcahey, M. A., Redout, E. M., Muller, A., Zuidwijk, M. J., Visser, T. J., et al. (2008). Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats. The Journal of Clinical Investigation, 118(3), 975–83. [DOI:10.1172/JCI32824] [DOI:10.1172/JCI32824]
41. Song, M., Jue, S. S., Cho, Y. A., & Kim, E. C. (2015). Comparison of the effects of human dental pulp stem cells and human bone marrow-derived mesenchymal stem cells on ischemic human astrocytes in vitro. Journal of Neuroscience Research, 93(4), 973–83. [DOI:10.1002/jnr.23569] [PMID] [DOI:10.1002/jnr.23569]
42. Southwell, A., Ko, J., & Patterson, P. (2009). Intrabody gene therapy ameliorates motor, cognitive, and neuropathological symptoms in multiple mouse models of Huntington's disease. Neuroscience, 29(6), 13589–602. [DOI:10.1523/JNEUROSCI.4286-09.2009] [PMID] [PMCID] [DOI:10.1523/JNEUROSCI.4286-09.2009]
43. Sung, J. H., Yang, H. M., Park, J. B., Choi, G. S., Joh, J. W., Kwon, C. H., et al. (2008). Isolation and characterization of mouse mesenchymal stem cells. Transplantation Proceedings, 40(4), 2649–54. [DOI:10.1016/j.transproceed.2008.08.009] [PMID] [DOI:10.1016/j.transproceed.2008.08.009]
44. Tan, Z., Li, X., & Kelly, K. (2009). Plasminogen activator inhibitor type 1 derived peptide, EEIIMD, diminishes cortical infarct but fails to improve neurological function in aged rats following middle cerebral artery occlusion. Brain Research, 24(1281), 84-90. [DOI:10.1016/j.brainres.2009.05.042] [PMID] [PMCID] [DOI:10.1016/j.brainres.2009.05.042]
45. Tang, Y., Wang, J., Lin, X., Wang, L., Shao, B., Jin, K., et al. (2014). Neural stem cell protects aged rat brain from ischemia–reperfusion injury through neurogenesis and angiogenesis. Journal of Cerebral Blood Flow & Metabolism, 34(1), 1138–47. [DOI:10.1038/jcbfm.2014.61] [PMID] [PMCID] [DOI:10.1038/jcbfm.2014.61]
46. Tatarishvili, J., Oki, K., Monni, E., Koch, P., Memanishvili, T., Buga, A. M., et al. (2014). Human induced pluripotent stem cells improve recovery in stroke-injured aged rats. Restorative Neurology and Neuroscience, 32(4), 547-58. [PMID] [PMID]
47. Vakili, A., Nekooeian, A., & Dehghani, G. A. (2004). L-NAME and 7-nitroindazole reduces brain injuries in transient focal cerebral ischemia in rat. Iranian Journal of Medical Sciences, 29(2), 109-15.
48. Wagner, D. C., Bojko, M., & Peters, M. (2012). Impact of age on the efficacy of bone marrow mononuclear cell transplantation in experimental stroke. Experimental & Translational Stroke Medicine, 4(17), 1-8. [DOI:10.1186/2040-7378-4-17] [PMID] [DOI:10.1186/2040-7378-4-17]
49. Zhang, Y., Cao, R., Jia, X., Li, Q., Qiao, L., Yan, G., & Yang, J. (2016). Treadmill exercise promotes neuroprotection against cerebral ischemia-reperfusion injury via downregulation of pro-inflammatory mediators. Neuropsychiatric Disesease Treatment, 12(3), 3161-73. [DOI:10.2147/NDT.S121779] [PMID] [PMCID] [DOI:10.2147/NDT.S121779]
50. Zhang, Y. X., Yuan, M. Z., Cheng, L., Lin, L. Z., Du, H. W., Chen, R. H., et al. (2015). Treadmill exercise enhances therapeutic potency of transplanted bone mesenchymal stem cells in cerebral ischemic rats via anti-apoptotic effects. BMC Neuroscience, 16, 56-61. [PMID] [PMCID] [DOI:10.1186/s12868-015-0196-9] [PMID] [PMCID]
51. Zhu, C., Wang, X., Xu, F., Bahr, B., Shibata, M., Uchiyama, Y., et al. (2005). The influence of age on apoptotic and other mechanisms of cell death after cerebral hypoxia–ischemia. Cell Death and Differentiation, 12(1), 162–76. [DOI:10.1038/sj.cdd.4401545] [PMID] [DOI:10.1038/sj.cdd.4401545]
52. Zhuo, Y., Li, S. H., Chen, M. S., Wu, J., Kinkaid, H. Y. M., Fazel, S., et al. (2010). Aging impairs the angiogenic response to ischemic injury and the activity of implanted cells: Combined consequences for cell therapy in older recipients. The Journal of Thoracic and Cardiovascular Surgery, 139(5), 1286-94. [DOI:10.1016/j.jtcvs.2009.08.052] [PMID] [DOI:10.1016/j.jtcvs.2009.08.052]
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