Rehabilitative treatment, including treadmill training, is considered an important strategy for restoring motor function after spinal cord injury (SCI). However, many unexplained problems persist regarding the appropriate rehabilitative method and the mechanism underlying the beneficial effects of rehabilitation. Moreover, only a few preclinical studies have been performed on rehabilitative interventions for chronic SCI, although most patients have chronic injuries. In fact, several preclinical studies reported that rehabilitative training was less effective when applied during the chronic phase than when applied sooner. While numerous studies have examined the effects of treadmill training during the subacute phase, the training conditions vary considerably among preclinical reports. Therefore, establishing a standard training protocol is essential for achieving beneficial rehabilitation effects at the chronic stage. Since the difficulty of applying an appropriate training load hinders training at constant speeds, it is important to adjust the training intensity in accordance with the exercise tolerance of an individual animal to provide further functional recovery benefits. Here, we created a novel quadrupedal treadmill training protocol based on the overload principle for mice with incomplete thoracic SCI. We subjected SCI model mice to rehabilitative training according to the protocol for two consecutive weeks starting at 42 days after injury. We examined the treadmill speeds at which the mice were able to run based on the severity of paresis and investigated the impact of the protocol on functional recovery. Assessment of running speed changes during the treadmill training period revealed faster treadmill speeds for mice with mild paresis than for those with severe paresis. The training parameters, including the speed and distance traveled, were positively correlated with the changes in motor function. These results suggest that the most suitable running speed during treadmill training differs according to the level of motor dysfunction and that running longer distances has a positive impact on motor functional recovery. Based on this established protocol, we compared functional and histological results between the chronic SCI groups with and without rehabilitation. The gait analyses showed significantly better functional improvement in the rehabilitation group than in the nonrehabilitation group. Histological analyses revealed that the BDNF- and VGLUT1-positive areas of lumbar enlargement were significantly increased in the rehabilitation group. These findings implied that rehabilitation promoted not only motor performance but also motor control, including forelimb-hindlimb coordination, even in chronic SCI, resulting in functional improvement by treadmill training alone. Therefore, rehabilitative training based on the overload principle appears to be one of the appropriate treatment options for incomplete thoracic SCI, and evidence of its efficacy exists in actual clinical settings.

康复治疗，包括跑步机训练，被认为是脊髓损伤 (SCI) 后恢复运动功能的重要策略。然而，关于适当的康复方法和康复有益效果的机制，许多无法解释的问题仍然存在。此外，尽管大多数患者患有慢性损伤，但仅对慢性 SCI 的康复干预进行了少数临床前研究。事实上，几项临床前研究报告说，在慢性期进行康复训练的效果不如较早进行。虽然许多研究已经检查了亚急性阶段跑步机训练的影响，但临床前报告的训练条件差异很大。所以，建立标准的训练方案对于在慢性阶段实现有益的康复效果至关重要。由于施加适当的训练负荷的困难阻碍了以恒定速度进行训练，因此根据个体动物的运动耐力调整训练强度以提供进一步的功能恢复益处非常重要。在这里，我们创建了一种基于超负荷原理的新型四足跑步机训练方案，适用于不完全胸椎 SCI 的小鼠。我们从受伤后 42 天开始，根据协议连续两周对 SCI 模型小鼠进行康复训练。我们根据麻痹的严重程度检查了小鼠能够跑步的跑步机速度，并研究了该协议对功能恢复的影响。对跑步机训练期间跑步速度变化的评估显示，轻度麻痹小鼠的跑步机速度比重度麻痹小鼠更快。训练参数，包括速度和行进距离，与运动功能的变化呈正相关。这些结果表明，跑步机训练期间最合适的跑步速度根据运动功能障碍的程度而有所不同，而长距离跑步对运动功能恢复有积极影响。基于这个既定的协议，我们比较了有和没有康复的慢性 SCI 组之间的功能和组织学结果。步态分析显示康复组的功能改善明显优于非康复组。组织学分析显示，康复组中腰椎增大的 BDNF 和 VGLUT1 阳性区域显着增加。这些发现表明，康复不仅促进运动表现，而且促进运动控制，包括前肢 - 后肢协调，即使在慢性 SCI 中，仅通过跑步机训练即可改善功能。因此，基于超负荷原则的康复训练似乎是不完全胸椎 SCI 的合适治疗选择之一，其有效性的证据存在于实际临床环境中。即使在慢性 SCI 中，仅通过跑步机训练就能改善功能。因此，基于超负荷原则的康复训练似乎是不完全胸椎 SCI 的合适治疗选择之一，其有效性的证据存在于实际临床环境中。即使在慢性 SCI 中，仅通过跑步机训练就能改善功能。因此，基于超负荷原则的康复训练似乎是不完全胸椎 SCI 的合适治疗选择之一，其有效性的证据存在于实际临床环境中。