Fong Andy J, Cai Lance L, Otoshi Chad K, Reinkensmeyer David J, Burdick Joel W, Roy Roland R, Edgerton V Reggie
Biomedical Engineering Interdepartmental Program, University of California, Los Angeles, California 90095, USA.
J Neurosci. 2005 Dec 14;25(50):11738-47. doi: 10.1523/JNEUROSCI.1523-05.2005.
In the present study, concurrent treatment with robotic step training and a serotonin agonist, quipazine, generated significant recovery of locomotor function in complete spinal cord-transected mice (T7-T9) that otherwise could not step. The extent of recovery achieved when these treatments were combined exceeded that obtained when either treatment was applied independently. We quantitatively analyzed the stepping characteristics of spinal mice after alternatively administering no training, manual training, robotic training, quipazine treatment, or a combination of robotic training with quipazine treatment, to examine the mechanisms by which training and quipazine treatment promote functional recovery. Using fast Fourier transform and principal components analysis, significant improvements in the step rhythm, step shape consistency, and number of weight-bearing steps were observed in robotically trained compared with manually trained or nontrained mice. In contrast, manual training had no effect on stepping performance, yielding no improvement compared with nontrained mice. Daily bolus quipazine treatment acutely improved the step shape consistency and number of steps executed by both robotically trained and nontrained mice, but these improvements did not persist after quipazine was withdrawn. At the dosage used (0.5 mg/kg body weight), quipazine appeared to facilitate, rather than directly generate, stepping, by enabling the spinal cord neural circuitry to process specific patterns of sensory information associated with weight-bearing stepping. Via this mechanism, quipazine treatment enhanced kinematically appropriate robotic training. When administered intermittently during an extended period of robotic training, quipazine revealed training-induced stepping improvements that were masked in the absence of the pharmacological treatment.
在本研究中，对完全脊髓横断（T7 - T9）且原本无法行走的小鼠，同时进行机器人辅助步态训练和给予5-羟色胺激动剂喹哌嗪治疗，使其运动功能得到显著恢复。联合治疗所实现的恢复程度超过了单独使用任何一种治疗方法时的效果。我们定量分析了在分别不进行训练、手动训练、机器人辅助训练、喹哌嗪治疗，或机器人辅助训练与喹哌嗪联合治疗后脊髓损伤小鼠的步态特征，以研究训练和喹哌嗪治疗促进功能恢复的机制。通过快速傅里叶变换和主成分分析发现，与手动训练或未训练的小鼠相比，接受机器人辅助训练的小鼠在步频、步形一致性和负重步数方面有显著改善。相比之下，手动训练对步态表现没有影响，与未训练的小鼠相比没有改善。每日给予大剂量喹哌嗪能急性改善接受机器人辅助训练和未训练小鼠的步形一致性和步数，但停用喹哌嗪后这些改善并未持续。在所使用的剂量（0.5毫克/千克体重）下，喹哌嗪似乎是通过使脊髓神经回路能够处理与负重步态相关的特定感觉信息模式来促进而非直接产生步态。通过这种机制，喹哌嗪治疗增强了运动学上合适的机器人辅助训练。在长时间的机器人辅助训练期间间歇性给予喹哌嗪时，发现了在没有药物治疗时被掩盖的训练诱导的步态改善。
