Baldwin Heather A, Koivula Pyry P, Necarsulmer Julie C, Whitaker Keith W, Harvey Brandon K
Cell Transplant. 2017 Apr 13;26(4):659-667. doi: 10.3727/096368916X693059. Epub 2016 Sep 26.
Parkinson's disease is a progressive neurological disorder, marked by the loss of dopaminergic neurons in the nigrostriatal pathway that leads to abnormal gait, rigidity, slowness of movement, and tremor. The ability to recapitulate and measure the neurological sequelae in rodent models of Parkinson's disease is important for studying and evaluating potential therapeutics. Individual variability in lesion severity and injury progression are key factors in the 6-hydroxydopamine model that require normalization when evaluating therapeutic effects. The gait parameters that were found to be affected by 6-hydroxydopamine lesioning of the nigrostriatal pathway in rats may be used to study novel transgenic models of Parkinson's disease as well as to test novel therapeutics. Previously, studies have used a video-based system to analyze gait abnormalities in the 6-hydroxydopamine model of Parkinson's disease, but these studies did not account for individual variability on reported gait parameters. By analyzing the ratio of parameters from the injured to uninjured sides and correcting for speed in related parameters, hindpaw step cycle parameters, hindpaw print area, and step sequence are significantly altered in different ways for each type of lesion, when compared to saline-injected controls. These findings enable new metrics for evaluating therapeutic efficacy of drug-, gene-, or cell-based therapies in rat models of Parkinson's disease.
帕金森病是一种进行性神经疾病，其特征是黑质纹状体通路中的多巴胺能神经元丧失，导致异常步态、僵硬、运动迟缓及震颤。在帕金森病啮齿动物模型中重现和测量神经后遗症的能力对于研究和评估潜在治疗方法至关重要。在6-羟基多巴胺模型中，损伤严重程度和损伤进展的个体差异是评估治疗效果时需要标准化的关键因素。已发现大鼠黑质纹状体通路的6-羟基多巴胺损伤所影响的步态参数，可用于研究帕金森病的新型转基因模型以及测试新型治疗方法。此前，已有研究使用基于视频的系统来分析帕金森病6-羟基多巴胺模型中的步态异常，但这些研究未考虑报告的步态参数的个体差异。通过分析损伤侧与未损伤侧参数的比率并校正相关参数中的速度，与注射生理盐水的对照组相比，每种损伤类型的后爪步周期参数、后爪印迹面积和步序均以不同方式发生显著改变。这些发现为评估帕金森病大鼠模型中基于药物、基因或细胞的治疗方法的疗效提供了新的指标。
