Jeffery Nick D, Brakel Kiralyn, Aceves Miriam, Hook Michelle A, Jeffery Unity B
Department of Small Animal Clinical Sciences, Texas A&M University, College Station, TX, United States.
Department of Neuroscience and Experimental Therapeutics, School of Medicine, Texas A&M University, Bryan, TX, United States.
Front Neurol. 2020 Jul 9;11:650. doi: 10.3389/fneur.2020.00650. eCollection 2020.
Spinal cord injury research in experimental animals aims to define mechanisms of tissue damage and identify interventions that can be translated into effective clinical therapies. Highly reliable models of injury and outcome measurement are essential to achieve these aims and avoid problems with reproducibility. Functional scoring is a critical component of outcome assessment and is currently commonly focused on open field locomotion (the "BBB score"). Here we analyze variability of observed locomotor outcome after a highly regulated spinal cord contusion in a large group of rats that had not received any therapeutic intervention. Our data indicate that, despite tight regulation of the injury severity, there is considerable variability in open-field score of individual rats at 21 days after injury, when the group as a whole reaches a functional plateau. The bootstrapped reference interval (that defines boundaries that contain 95% scores in the population without regard for data distributional character) for the score at 21 days was calculated to range from 2.3 to 15.9 on the 22-point scale. Further analysis indicated that the mean day 21 score of random groups of 10 individuals drawn by bootstrap sampling from the whole study population varies between 9.5 and 13.5. Wide variability between individuals implies that detection of small magnitude group-level treatment effects will likely be unreliable, especially if using small experimental group sizes. To minimize this problem in intervention studies, consideration should be given to assessing treatment effects by comparing proportions of animals in comparator groups that attain pre-specified criterion scores.
实验动物的脊髓损伤研究旨在明确组织损伤机制，并确定可转化为有效临床治疗方法的干预措施。高度可靠的损伤模型和结果测量方法对于实现这些目标以及避免可重复性问题至关重要。功能评分是结果评估的关键组成部分，目前通常侧重于旷场运动（“BBB评分”）。在此，我们分析了一大群未接受任何治疗干预的大鼠在受到高度规范的脊髓挫伤后观察到的运动结果的变异性。我们的数据表明，尽管对损伤严重程度进行了严格控制，但在损伤后21天，当整个群体达到功能平台期时，个体大鼠的旷场评分仍存在相当大的变异性。计算得出，在22分制中，21天时评分的自抽样参考区间（该区间定义了包含总体中95%评分的边界，而不考虑数据分布特征）为2.3至15.9。进一步分析表明，通过自抽样从整个研究群体中抽取的每组10只个体的随机组在第21天的平均评分在9.5至13.5之间变化。个体之间的广泛变异性意味着检测小幅度的组水平治疗效果可能不可靠，特别是在使用小实验组规模的情况下。为了在干预研究中尽量减少这个问题，应考虑通过比较达到预先指定标准评分的比较组中动物的比例来评估治疗效果。
