Stem Cell Center, Department of Education and Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.
J Neurosurg. 2013 Mar;118(3):594-605. doi: 10.3171/2012.8.JNS111580. Epub 2012 Nov 23.
Object Mobilization of hematopoietic progenitor cells (HPCs) from bone marrow involved in the process of peripheral nerve regeneration occurs mostly through deposits of CD34(+) cells. Treadmill exercise, with either differing intensity or duration, has been shown to increase axon regeneration and sprouting, but the effect of mobilization of HPCs on peripheral nerve regeneration due to treadmill exercise has not yet been elucidated. Methods Peripheral nerve injury was induced in Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were categorized into 2 groups: those with and without treadmill exercise (20 m/min for 60 minutes per day for 7 days). Cytospin and flow cytometry were used to determine bone marrow progenitor cell density and distribution. Neurobehavioral analysis, electrophysiological study, and regeneration marker expression were investigated at 1 and 3 weeks after exercise. The accumulation of HPCs, immune cells, and angiogenesis factors in injured nerves was determined. A separate chimeric mice study was conducted to assess CD34(+) cell distribution according to treadmill exercise group. Results Treadmill exercise significantly promoted nerve regeneration. Increased Schwann cell proliferation, increased neurofilament expression, and decreased Schwann cell apoptosis were observed 7 days after treadmill exercise. Elevated expression of S100 and Luxol fast blue, as well as decreased numbers of vacuoles, were identified in the crushed nerve 3 weeks after treadmill exercise. Significantly increased numbers of mononuclear cells, particularly CD34(+) cells, were induced in bone marrow after treadmill exercise. The deposition of CD34(+) cells was abolished by bone marrow irradiation. In addition, deposits of CD34(+) cells in crushed nerves paralleled the elevated expressions of von Willebrand factor, isolectin B4, and vascular endothelial growth factor. Conclusions Bone marrow HPCs, especially CD34(+) cells, were able to be mobilized by low-intensity treadmill exercise, and this effect paralleled the significant expression of angiogenesis factors. Treadmill exercise stimulation of HPC mobilization during peripheral nerve regeneration could be used as a therapy in human beings.
从骨髓中动员造血祖细胞（HPC）参与周围神经再生的过程主要通过 CD34(+)细胞的沉积来实现。不同强度或时间的跑步机运动已被证明可以增加轴突再生和发芽，但跑步机运动对周围神经再生的 HPC 动员效应尚未阐明。
通过血管夹夹伤左侧坐骨神经在 Sprague-Dawley 大鼠中诱导周围神经损伤。将动物分为两组：有跑步机运动组（每天 20m/min 运动 60 分钟，持续 7 天）和无跑步机运动组。使用细胞涂片和流式细胞术来确定骨髓祖细胞密度和分布。在运动后 1 周和 3 周进行神经行为分析、电生理学研究和再生标志物表达检测。测定损伤神经中 HPC、免疫细胞和血管生成因子的积累。进行了一项单独的嵌合小鼠研究，以根据跑步机运动组评估 CD34(+)细胞的分布。
跑步机运动显著促进了神经再生。跑步机运动 7 天后，观察到雪旺细胞增殖增加、神经丝表达增加和雪旺细胞凋亡减少。跑步机运动 3 周后，在夹伤神经中发现 S100 和 Luxol 快速蓝表达增加，空泡数量减少。跑步机运动后骨髓中单核细胞，特别是 CD34(+)细胞的数量明显增加。骨髓照射可消除 CD34(+)细胞的沉积。此外，CD34(+)细胞在夹伤神经中的沉积与血管内皮生长因子、同工凝集素 B4 和 von Willebrand 因子的表达升高相平行。
低强度跑步机运动能够动员骨髓中的 HPC，特别是 CD34(+)细胞，这种效应与血管生成因子的显著表达相平行。在周围神经再生过程中，跑步机运动刺激 HPC 动员可能被用于人类治疗。
