Lai Stefano, Panarese Alessandro, Lawrence Ross, Boninger Michael L, Micera Silvestro, Ambrosio Fabrisia
1Scuola Superiore Sant'Anna, Translational Neural Engineering Area, The BioRobotics Institute, Pisa, ITALY; 2Department of Physical Medicine and Rehabilitation, University of Pittsburgh, Pittsburgh, PA; 3McGowan Institute for Regenerative Medicine, University of Pittsburgh Medical Center, University of Pittsburgh, Pittsburgh, PA; 4Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA; 5Department of Rehabilitation Science and Technology, University of Pittsburgh, Pittsburgh, PA; and 6Ecole Polytechnique Federale de Lausanne (EPFL), Bertarelli Foundation Chair in Translational NeuroEngineering Laboratory, Center for Neuroprosthetics and Institute of Bioengineering, Lausanne, SWITZERLAND.
Med Sci Sports Exerc. 2017 Apr;49(4):840-847. doi: 10.1249/MSS.0000000000001160.
In vivo studies have suggested that motor exercise can improve muscle regeneration after injury. Nevertheless, preclinical investigations still lack reliable tools to monitor motor performance over time and to deliver optimal training protocols to maximize force recovery. Here, we evaluated the utility of a murine robotic platform (i) to detect early impairment and longitudinal recovery after acute skeletal muscle injury and (ii) to administer varying intensity training protocols to enhance forelimb motor performance.
A custom-designed robotic platform was used to train mice to perform a forelimb retraction task. After an acute injury to bilateral biceps brachii muscles, animals performed a daily training protocol in the platform at high (HL) or low (LL) loading levels over the course of 3 wk. Control animals were not trained (NT). Motor performance was assessed by quantifying force, time, submovement count, and number of movement attempts to accomplish the task. Myofiber number and cross-sectional area at the injury site were quantified histologically.
Two days after injury, significant differences in the time, submovement count, number of movement attempts, and exerted force were observed in all mice, as compared with baseline values. Interestingly, the recovery time of muscle force production differed significantly between intervention groups, with HL group showing a significantly accelerated recovery. Three weeks after injury, all groups showed motor performance comparable with baseline values. Accordingly, there were no differences in the number of myofibers or average cross-sectional area among groups after 3 wk.
Our findings demonstrate the utility of our custom-designed robotic device for the quantitative assessment of skeletal muscle function in preclinical murine studies. Moreover, we demonstrate that this device may be used to apply varying levels of resistance longitudinally as a means manipulate physiological muscle responses.
体内研究表明,运动锻炼可改善损伤后的肌肉再生。然而,临床前研究仍缺乏可靠工具来长期监测运动表现,并提供最佳训练方案以最大程度地促进力量恢复。在此,我们评估了一种小鼠机器人平台的效用:(i)检测急性骨骼肌损伤后的早期功能障碍和纵向恢复情况;(ii)实施不同强度的训练方案以增强前肢运动表现。
使用定制设计的机器人平台训练小鼠执行前肢回缩任务。双侧肱二头肌急性损伤后,动物在平台上于高负荷(HL)或低负荷(LL)水平进行为期3周的每日训练方案。对照动物不进行训练(NT)。通过量化完成任务所需的力量、时间、子动作计数和运动尝试次数来评估运动表现。对损伤部位的肌纤维数量和横截面积进行组织学定量分析。
与基线值相比,损伤后两天,所有小鼠在时间、子动作计数、运动尝试次数和施加的力量方面均出现显著差异。有趣的是,各干预组之间肌肉力量产生的恢复时间存在显著差异,HL组显示恢复明显加速。损伤后三周,所有组的运动表现均与基线值相当。因此,三周后各组之间的肌纤维数量或平均横截面积无差异。
我们的研究结果证明了我们定制设计的机器人装置在临床前小鼠研究中对骨骼肌功能进行定量评估的效用。此外,我们证明该装置可用于纵向施加不同水平的阻力,作为操纵生理性肌肉反应的一种手段。