Determining the source of variability within experimental stroke models

确定实验性卒中模型中变异的来源

• 批准号: NC/M000117/1
• 负责人: Claire Gibson
• 金额: $ 9.5万
• 依托单位: University of Leicester
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=NC%2FM000117%2F1
• 关键词: Determining; source; variability; within; experimental

In the UK, cerebral stroke is the 3rd cause of death, the leading cause of severe adult disability in adults and costs the NHS an estimated £3 billion per year. The generation of novel and rational therapeutics is essential. Thus, every year thousands of animals are used experimentally to model stroke and investigate potential therapies. Mice are commonly used in experimental studies aimed at modelling stroke not least because they are useful for genetic manipulation studies. However, studies using eperimental stroke models tend to show a large variabiity in the data produced. This usually results in researchers using increased number of animals per study in order to try and detect a significant difference. We propose that a large portion of this variability may be due to differences in the anatomy of blood vessels in the brain. Such variability has been well documented in anatomical studies and we propose here the introduction of a non-invasive screening process whereby those animal with the highest degree of variability can be excluded from studies prior to them undergoing experimental stroke. Thus, this should reduce the variability in data obtained from using experimetnal stroke models and therefore reduce the number of animals undergoing such procedures. In addition, we intend to deternine with a variation in the established protocol for inducing experimental stroke can also result in a reduction in the variability of data and therefore reduce the number of animals used in such experiments.

在英国，中风是第三大死亡原因，是成人严重残疾的主要原因，据估计，NHS每年要花费30亿英镑。新的和合理的治疗方法的产生是必不可少的。因此，每年都有数以千计的动物被实验性地用于建立中风模型和研究潜在的治疗方法。老鼠通常被用于旨在模拟中风的实验研究中，尤其是因为它们对基因操作研究很有用。然而，使用实验性中风模型的研究倾向于显示所产生的数据存在很大的差异。这通常会导致研究人员在每项研究中使用更多的动物，以试图发现显著的差异。我们认为，这种可变性的很大一部分可能是由于大脑中血管的解剖结构的差异。这种变异性已经在解剖学研究中得到了很好的证明，我们建议引入一种非侵入性的筛查程序，通过这种程序，那些变异性程度最高的动物可以在接受实验性中风之前的研究中被排除在外。因此，这应该会减少使用实验性中风模型获得的数据的可变性，从而减少经历这种程序的动物数量。此外，我们打算确定在已建立的诱发实验性中风的方案中的变化也可以导致数据的变异性，从而减少在此类实验中使用的动物数量。