Chang Min Cheol, Park Chae Ri, Rhie Seung Hwa, Shim Woo Hyun, Kim Dae Yul
Department of Rehabilitation Medicine, College of Medicine, Yeungnam University, Daegu, Republic of Korea.
Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Neural Regen Res. 2019 Jul;14(7):1230-1236. doi: 10.4103/1673-5374.251330.
The neuroprotective function of macrophage migration inhibitory factor (MIF) in ischemic stroke was rarely evaluated. This study aimed to investigate the effects of early treadmill exercise on recovery from ischemic stroke and to determine whether these effects are associated with the expression levels of MIF and brain-derived neurotrophic factor (BDNF) in the ischemic area. A total of 40 male Sprague-Dawley rats were randomly assigned to the ischemia and exercise group [middle cerebral artery occlusion (MCAO)-Ex, n = 10), ischemia and sedentary group (MCAO-St, n = 10), sham-surgery and exercise group (Sham-Ex, n = 10), or sham-surgery and sedentary group (Sham-St, n = 10). The MCAO-Ex and MCAO-St groups were subjected to MCAO for 60 minutes, whereas the Sham-Ex and Sham-St groups were subjected to an identical operation without MCAO. Rats in the MCAO-Ex and Sham-Ex groups then ran on a treadmill for 30 minutes once a day for 5 consecutive days. After reperfusion, the hanging time tested by the wire hang test was longer and the relative fractional anisotropy determined by MRI was higher in the peri-infarct region of the MCAO-Ex group compared with the MCAO-St group. The expression levels of MIF and BDNF in the peri-infarct region were upregulated in the MCAO-Ex group. Increased MIF and BDNF levels were positively correlated with relative fractional anisotropy changes in the peri-infarct region. There was no significant difference in the levels of MIF and BDNF in the peri-infarct region between the Sham-Ex and Sham-St groups. Our study demonstrated that early exercise (initiated 48 hours after the MCAO) could improve motor and neuronal recovery after ischemic stroke. Furthermore, the increased levels of MIF and BDNF in the peri-infarct region (penumbra) may be one of the mechanisms of enhanced neurological function recovery. All experiments were approved by the Institutional Animal Care and Use Committee in Asan Medical Center in South Korea (2016-12-126).
巨噬细胞移动抑制因子（MIF）在缺血性卒中中的神经保护功能鲜有评估。本研究旨在探讨早期跑步机运动对缺血性卒中恢复的影响，并确定这些影响是否与缺血区域中MIF和脑源性神经营养因子（BDNF）的表达水平相关。总共40只雄性Sprague-Dawley大鼠被随机分配至缺血与运动组[大脑中动脉闭塞（MCAO）-Ex，n = 10]、缺血与久坐组（MCAO-St，n = 10）、假手术与运动组（Sham-Ex，n = 10）或假手术与久坐组（Sham-St，n = 10）。MCAO-Ex组和MCAO-St组进行60分钟的MCAO，而Sham-Ex组和Sham-St组进行相同手术但不进行MCAO。MCAO-Ex组和Sham-Ex组的大鼠随后每天在跑步机上跑30分钟，连续跑5天。再灌注后，与MCAO-St组相比，MCAO-Ex组梗死灶周围区域通过悬线试验测得的悬挂时间更长，通过MRI测定的相对各向异性分数更高。MCAO-Ex组梗死灶周围区域MIF和BDNF的表达水平上调。MIF和BDNF水平升高与梗死灶周围区域相对各向异性分数变化呈正相关。Sham-Ex组和Sham-St组梗死灶周围区域MIF和BDNF水平无显著差异。我们的研究表明，早期运动（在MCAO后48小时开始）可改善缺血性卒中后的运动和神经恢复。此外，梗死灶周围区域（半暗带）中MIF和BDNF水平升高可能是神经功能恢复增强的机制之一。所有实验均获得韩国峨山医疗中心机构动物护理和使用委员会的批准（2016-12-126）。
