Unité INSERM U1093 Cognition, Action et Plasticité Sensorimotrice, Dijon, France.
PLoS One. 2012;7(9):e44218. doi: 10.1371/journal.pone.0044218. Epub 2012 Sep 4.
Physical exercise constitutes an innovative strategy to treat deficits associated with stroke through the promotion of BDNF-dependent neuroplasticity. However, there is no consensus on the optimal intensity/duration of exercise. In addition, whether previous stroke changes the effect of exercise on the brain is not known. Therefore, the present study compared the effects of a clinically-relevant form of exercise on cerebral BDNF levels and localization in control versus stroke rats. For this purpose, treadmill exercise (0.3 m/s, 30 min/day, for 7 consecutive days) was started in rats with a cortical ischemic stroke after complete maturation of the lesion or in control rats. Sedentary rats were run in parallel. Mature and proBDNF levels were measured on the day following the last boot of exercise using Western blotting analysis. Total BDNF levels were simultaneously measured using ELISA tests. As compared to the striatum and the hippocampus, the cortex was the most responsive region to exercise. In this region, exercise resulted in a comparable increase in the production of mature BDNF in intact and stroke rats but increased proBDNF levels only in intact rats. Importantly, levels of mature BDNF and synaptophysin were strongly correlated. These changes in BDNF metabolism coincided with the appearance of intense BDNF labeling in the endothelium of cortical vessels. Notably, ELISA tests failed to detect changes in BDNF forms. Our results suggest that control beings can be used to find conditions of exercise that will result in increased mBDNF levels in stroke beings. They also suggest cerebral endothelium as a potential source of BDNF after exercise and highlight the importance to specifically measure the mature form of BDNF to assess BDNF-dependent plasticity in relation with exercise.
体育锻炼是一种通过促进 BDNF 依赖的神经可塑性来治疗与中风相关缺陷的创新策略。然而,对于最佳运动强度/持续时间尚未达成共识。此外,之前的中风是否会改变运动对大脑的影响也不得而知。因此,本研究比较了控制组和中风大鼠接受一种临床相关形式的运动对大脑 BDNF 水平和定位的影响。为此,在皮质缺血性中风后,在病变完全成熟后或在对照组大鼠中开始进行跑步机运动(0.3 m/s,30 分钟/天,连续 7 天)。同时,对久坐不动的大鼠进行平行运行。在最后一次启动运动后的第二天,使用 Western blot 分析测量成熟和 proBDNF 水平。同时使用 ELISA 测试测量总 BDNF 水平。与纹状体和海马体相比,皮质是对运动反应最敏感的区域。在该区域,运动导致完整和中风大鼠成熟 BDNF 的产生增加相当,但仅在完整大鼠中增加 proBDNF 水平。重要的是,成熟 BDNF 和突触小体素水平之间存在强烈的相关性。BDNF 代谢的这些变化与皮质血管内皮中强烈的 BDNF 标记的出现同时发生。值得注意的是,ELISA 测试未能检测到 BDNF 形式的变化。我们的结果表明,可以使用对照动物来寻找能导致中风动物中 mBDNF 水平增加的运动条件。它们还表明,大脑内皮细胞可能是运动后 BDNF 的潜在来源,并强调了专门测量成熟形式的 BDNF 以评估与运动相关的 BDNF 依赖性可塑性的重要性。