Akhoundzadeh Kobra, Vakili Abedin, Sameni Hamid Reza
Physiology Research Center, Semnan University of Medical Sciences, Semnan, Iran.
Department of Nursing, School of Nursing & Midwifery, Qom University of Medical Sciences, Qom, Iran.
Basic Clin Neurosci. 2019 Jan-Feb;10(1):73-84. doi: 10.32598/bcn.9.10.355. Epub 2019 Jan 1.
Based on our previous findings, the treatment of stem cells alone or in combination with thyroid hormone (T) 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 T and mild treadmill exercise can decrease stroke complications in middle-aged mice.
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 (1×10) were injected into the right cerebral ventricle 24 h after MCAO, followed by daily injection of triiodothyronine (T) (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.
Post-ischemic treatment with BMSCs or with T 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 T (P<0.01).
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.
基于我们之前的研究结果，单独使用干细胞或联合甲状腺激素（T）及轻度运动进行治疗，可有效降低年轻小鼠中风损伤的风险。然而，目前尚不清楚这种治疗方法对老年或中年小鼠是否有效。因此，本研究旨在评估骨髓基质细胞（BMSC）联合T及轻度跑步机运动能否降低中年小鼠的中风并发症。
在激光多普勒血流仪监测下，通过右侧大脑中动脉闭塞（MCAO）45分钟，然后在中年小鼠中进行7天的再灌注，造成短暂性局灶性脑缺血。在MCAO后24小时，将BMSC（1×10）注入右侧脑室，随后每日注射三碘甲状腺原氨酸（T）（20μg/100g/d，皮下注射），并在跑步机上跑步6天。在中风后1周评估梗死面积、神经功能、凋亡细胞和胶质纤维酸性蛋白（GFAP）的表达水平。
在中年小鼠缺血7天后，单独或联合使用BMSC、T或轻度跑步机运动进行缺血后治疗，均未显著改变神经功能、梗死面积和凋亡细胞（P>0.05）。然而，用BMSC和/或T治疗后，GFAP的表达显著降低（P<0.01）。
我们的研究结果表明，在中年小鼠缺血7天后，中风后用BMSC联合运动和甲状腺激素治疗不能逆转神经元损伤。这些发现进一步支持年龄是中风治疗中的一个重要变量。
