Institute of Biomedical Engineering, National Cheng Kung University, Tainan, Taiwan.
Behav Brain Res. 2011 Sep 12;222(1):1-9. doi: 10.1016/j.bbr.2011.03.031. Epub 2011 Mar 22.
Gait disturbances similar to those of human Parkinson's disease (PD) can be observed in animals after administration of neurotoxin 6-hydroxydopamine (6-OHDA) to induce unilateral nigrostriatal dopamine depletion. However, the relationship between gait disturbances and dopamine depletion following 6-OHDA infusion has not been determined. The present study investigated the longitudinal changes of spatiotemporal gait patterns using a walkway system to acquire footprints and lateral limb images over a 6-week period following unilateral 6-OHDA injection into the medial forebrain bundle of rats. Our results indicated that hemiparkinsonian rats exhibited changes in gait patterns, as compared to normal controls, and pre-lesion levels, including a significantly decreased walking speed and step/stride length as well as an increased base of support and foot angle. The relative percentage of the gait cycle was also altered, showing an increase in the stance to swing ratio, which was more evident in the affected hindlimb. Time-course observations showed that these gait disturbances occurred as early as 4 days post-lesion and gradually increased up to 42 days post-injury. The extents of gait disturbances were compared with conventional apomorphine-induced turning behavior and akinesia bar tests, which were also apparent at 4 days post-lesion but remained relatively unchanged after 28 days. Our time-course gait analysis of a unilateral 6-OHDA rodent model provides insight into the compensatory changes of motor functions during the 6-week development of a nigrostriatal lesion, which might be useful for future objective assessment of novel treatments for human PD subjects.
在向动物中注射神经毒素 6-羟多巴胺（6-OHDA）以诱导单侧黑质纹状体多巴胺耗竭后，可以观察到类似于人类帕金森病（PD）的步态障碍。然而，6-OHDA 输注后步态障碍与多巴胺耗竭之间的关系尚未确定。本研究使用步道系统在单侧内侧前脑束注射 6-OHDA 后 6 周内采集足迹和肢体图像，对时空步态模式的纵向变化进行了研究。我们的结果表明，与正常对照组相比，半帕金森大鼠的步态模式发生了变化，包括行走速度和步幅/步长明显降低以及支撑基底和足角增加。步态周期的相对百分比也发生了改变，表现为支撑期与摆动期的比例增加，在受影响的后肢更为明显。时程观察表明，这些步态障碍早在损伤后 4 天就出现，并逐渐增加，直至损伤后 42 天。步态障碍的严重程度与传统的阿朴吗啡诱导的转向行为和运动不能棒测试进行了比较，这两种行为在损伤后 4 天也很明显，但在 28 天后相对不变。我们对单侧 6-OHDA 啮齿动物模型的时程步态分析提供了对黑质纹状体损伤 6 周发展过程中运动功能代偿变化的深入了解，这可能对未来评估人类 PD 患者新疗法的客观评估有用。
