Kondo Takahiro, Saito Risa, Sato Yuta, Sato Kenta, Uchida Akito, Yoshino-Saito Kimika, Shinozaki Munehisa, Tashiro Syoichi, Nagoshi Narihito, Nakamura Masaya, Ushiba Junichi, Okano Hideyuki
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
Graduate School of Science and Technology, Keio University, Yokohama, Japan.
Front Cell Neurosci. 2022 Apr 22;16:858562. doi: 10.3389/fncel.2022.858562. eCollection 2022.
Spinal cord injury (SCI) leads to locomotor dysfunction. Locomotor rehabilitation promotes the recovery of stepping ability in lower mammals, but it has limited efficacy in humans with a severe SCI. To explain this discrepancy between different species, a nonhuman primate rehabilitation model with a severe SCI would be useful. In this study, we developed a rehabilitation model of paraplegia caused by a severe traumatic SCI in a nonhuman primate, common marmoset (). The locomotor rating scale for marmosets was developed to accurately assess the recovery of locomotor functions in marmosets. All animals showed flaccid paralysis of the hindlimb after a thoracic contusive SCI, but the trained group showed significant locomotor recovery. Kinematic analysis revealed significantly improved hindlimb stepping patterns in trained marmosets. Furthermore, intracortical microstimulation (ICMS) of the motor cortex evoked the hindlimb muscles in the trained group, suggesting the reconnection between supraspinal input and the lumbosacral network. Because rehabilitation may be combined with regenerative interventions such as medicine or cell therapy, this primate model can be used as a preclinical test of therapies that can be used in human clinical trials.
脊髓损伤(SCI)会导致运动功能障碍。运动康复可促进低等哺乳动物步行动力的恢复,但对严重脊髓损伤的人类疗效有限。为解释不同物种间的这种差异,建立一个严重脊髓损伤的非人灵长类动物康复模型会很有帮助。在本研究中,我们在普通狨猴这种非人灵长类动物中建立了由严重创伤性脊髓损伤导致截瘫的康复模型。开发了狨猴运动评分量表以准确评估狨猴运动功能的恢复情况。所有动物在胸段挫伤性脊髓损伤后均出现后肢弛缓性麻痹,但训练组显示出显著的运动恢复。运动学分析显示训练后的狨猴后肢步行动态有显著改善。此外,对训练组运动皮层进行皮质内微刺激(ICMS)可诱发后肢肌肉反应,提示脊髓上输入与腰骶网络之间重新建立了连接。由于康复可能会与药物或细胞治疗等再生干预措施相结合,该灵长类动物模型可作为可用于人类临床试验的疗法的临床前测试模型。