Terashi Takuto, Otsuka Shotaro, Takada Seiya, Nakanishi Kazuki, Ueda Koki, Sumizono Megumi, Kikuchi Kiyoshi, Sakakima Harutoshi
a Course of Physical Therapy, School of Health Sciences, Faculty of Medicine , Kagoshima University , Kagoshima , Japan.
b Division of Brain Science, Department of Physiology , Kurume University School of Medicine , Kurume , Japan.
Neurol Res. 2019 Jun;41(6):510-518. doi: 10.1080/01616412.2019.1580458. Epub 2019 Mar 1.
Preconditioning exercise can exert neuroprotective effects after stroke; however, the effects of exercise intensity, frequency, duration are unknown. We investigated the neuroprotective effect of different frequency preconditioning exercise on neuronal apoptosis after cerebral ischemia in rats.
Rats were divided into the following five groups: 5 times a week of exercise (5/w-Ex) group, 3 times a week of exercise (3/w-Ex) group, once a week of exercise (1/w-Ex) group, no exercise (No-Ex) group, and intact control (control) group. Rats were made to run on a treadmill for 30 min per day at a speed of 25 m/min for 3 weeks. After the running program, the rats were subjected to 60-min left middle cerebral artery occlusion. Two days after ischemia, the cerebral infarct volume, neurological and motor function, Bcl-2-associated X protein (Bax)/B-cell lymphoma 2 (Bcl-2) ratio, expression of caspase-3, and TUNEL positive cells were examined in the cerebral cortex surrounding the ischemic zone.
The 3/w-Ex and 5/w-Ex groups showed significantly reduced infarct volumes compared with the No-Ex group, but the 1/w-Ex group did not. In addition, the 3/w-Ex and 5/w-Ex groups had improved neurological scores and sensorimotor function compared with the No-Ex group. The Bax/Bcl-2 ratio, expression of caspase-3, and TUNEL-positive cells significantly decreased in the penumbra area in the 3/w-Ex or 5/w-Ex groups compared with the No-Ex group.
Our findings suggested that three times or more per week of high-intensity preconditioning exercise exert neuroprotective effects through the downregulation of the Bax/Bcl-2 ratio and caspase-3 activation after stroke.
TUNEL: terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick and labeling; MCAO:middle cerebral artery occlusion; BAX:Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; TTC: 2,3,5-triphenyltetrazorlium chloride.
预处理运动可在中风后发挥神经保护作用；然而，运动强度、频率、持续时间的影响尚不清楚。我们研究了不同频率的预处理运动对大鼠脑缺血后神经元凋亡的神经保护作用。
将大鼠分为以下五组：每周运动5次（5/w-Ex）组、每周运动3次（3/w-Ex）组、每周运动1次（1/w-Ex）组、不运动（No-Ex）组和完整对照组（control）。让大鼠在跑步机上以25米/分钟的速度每天跑30分钟，持续3周。跑步程序结束后，对大鼠进行60分钟的左侧大脑中动脉闭塞。缺血两天后，检测缺血区周围大脑皮层的脑梗死体积、神经和运动功能、Bcl-2相关X蛋白（Bax）/B细胞淋巴瘤2（Bcl-2）比值、半胱天冬酶-3的表达以及TUNEL阳性细胞。
与No-Ex组相比，3/w-Ex组和5/w-Ex组的梗死体积显著减小，但1/w-Ex组没有。此外，与No-Ex组相比，3/w-Ex组和5/w-Ex组的神经评分和感觉运动功能有所改善。与No-Ex组相比，3/w-Ex组或5/w-Ex组半暗带区域的Bax/Bcl-2比值、半胱天冬酶-3的表达以及TUNEL阳性细胞显著减少。
我们的研究结果表明，每周三次或更多次的高强度预处理运动通过下调中风后Bax/Bcl-2比值和半胱天冬酶-3激活发挥神经保护作用。
TUNEL：末端脱氧核苷酸转移酶介导的生物素化dUTP缺口末端标记；MCAO：大脑中动脉闭塞；BAX：Bcl-2相关X蛋白；Bcl-2：B细胞淋巴瘤2；TTC：2,3,5-三苯基氯化四氮唑
