Severity assessment in neuroscientific research: generalisability of multidimensional approaches and application to refinement
神经科学研究中的严重性评估:多维方法的普遍性和细化的应用
基本信息
- 批准号:329777818
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:德国
- 项目类别:Research Units
- 财政年份:
- 资助国家:德国
- 起止时间:
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
During funding phase 1 and 2, a comprehensive set of behavioural, biochemical, and telemetrically-analysed physiological parameters has been assessed in various induced and genetic mouse and rat models of neuropediatric and neurological disorders. A cross-age, -model, -species and -sex validation provided valuable information about generalisability of selected parameter candidates. Respective information was considered for the design and validation of a test battery allowing assessment of cumulative severity across the developmental trajectory of young genetically-modified mice. Moreover, we have further developed, and optimised a bioinformatic workflow for parameter selection and design of multidimensional composite measure schemes. Case studies, focussed on models of epilepsy, neurodevelopmental and neuropsychiatric disorders, demonstrated that the resulting multidimensional schemes take severity assessment to a new level of sensitivity allowing comparative assessment with precise grading of distress levels. Multivariate approaches have also been successfully applied to validate potential refinement measures (e.g., optimised multimodal analgesia; telemetric vs. tethered recordings) for common interventions and techniques in neuroscientific research. Findings from experimental studies and systematic reviews serve as a basis for selecting the most promising parameters for an in-depth intra-laboratory and an overarching inter-laboratory analysis, providing further information about their informative value, sensitivity, replicability, robustness, and generalisability. Along these lines, the bioinformatic workflow for the design of multidimensional composite measure schemes will be applied to datasets from different collaboration partners to confirm its validity for different animal models and identify necessary adaptations. In addition, we will apply RELSA to our data sets to confirm the validity of this multidimensional scoring system for continuous severity monitoring and will support the development of variants for specific study designs. In terms of evidence-based refinement, analysis of intra- and inter-laboratory data and routine use of multimodal perioperative analgesic regimens will inform about the generalisability of such regimens. With data sets recorded during a multicentre study with transmitter implants and from a genetic mouse model, we will contribute to the validation of a new smart home cage system. Based on our findings and discussions with stakeholders, we will provide recommendations for the design and application of multivariate schemes for evidence-based severity assessment and for evidence-based refinement measures.
在资助第一阶段和第二阶段期间,在神经儿科和神经系统疾病的各种诱导和遗传小鼠和大鼠模型中评估了一套全面的行为、生化和遥测分析的生理参数。跨年龄、模型、物种和性别验证提供了有关所选参数候选者的普遍性的有价值的信息。测试电池的设计和验证考虑了各自的信息,从而可以评估年轻转基因小鼠整个发育轨迹的累积严重程度。此外,我们还进一步开发和优化了用于参数选择和多维复合测量方案设计的生物信息学工作流程。专注于癫痫、神经发育和神经精神疾病模型的案例研究表明,由此产生的多维方案将严重性评估提升到了新的敏感性水平,从而可以通过精确的痛苦程度分级进行比较评估。多变量方法也已成功应用于验证神经科学研究中常见干预措施和技术的潜在细化措施(例如,优化的多模式镇痛;遥测与系留记录)。实验研究和系统评价的结果可作为选择最有希望的参数进行深入实验室内和总体实验室间分析的基础,提供有关其信息价值、敏感性、可复制性、稳健性和普遍性的进一步信息。沿着这些思路,用于设计多维复合测量方案的生物信息学工作流程将应用于来自不同合作伙伴的数据集,以确认其对不同动物模型的有效性并确定必要的适应。此外,我们将把 RELSA 应用到我们的数据集中,以确认这个多维评分系统用于持续严重性监测的有效性,并将支持特定研究设计的变体开发。在基于证据的改进方面,对实验室内和实验室间数据的分析以及多模式围手术期镇痛方案的常规使用将有助于了解此类方案的普遍性。利用在多中心研究期间使用发射器植入物和遗传小鼠模型记录的数据集,我们将有助于验证新的智能家居笼系统。根据我们的发现以及与利益相关者的讨论,我们将为基于证据的严重性评估和基于证据的细化措施的多变量方案的设计和应用提供建议。
项目成果
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Professorin Dr. Heidrun Potschka其他文献
Professorin Dr. Heidrun Potschka的其他文献
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{{ truncateString('Professorin Dr. Heidrun Potschka', 18)}}的其他基金
Functional role of HSP70 expression regulation in the pathogenesis of epilepsy and associated inflammatory processes
HSP70 表达调节在癫痫发病机制及相关炎症过程中的功能作用
- 批准号:
317933165 - 财政年份:2016
- 资助金额:
-- - 项目类别:
Research Grants
Modulation der Mikrogliafunktion zur Erkrankungsmodifikation und Prävention von Epilepsien
调节小胶质细胞功能以改善疾病和预防癫痫
- 批准号:
117328898 - 财政年份:2009
- 资助金额:
-- - 项目类别:
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Validierung neuer Strategien zur Prophylaxe oder Überwindung Multidrug-Transporter-basierter Pharmakoresistenz
验证预防或克服基于多药转运蛋白的药物耐药性的新策略
- 批准号:
25187073 - 财政年份:2006
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The Sigma1 protein as a target for therapeutic management of epilepsy: preclinical validation in chronic mouse models
Sigma1 蛋白作为癫痫治疗管理的靶标:慢性小鼠模型的临床前验证
- 批准号:
494080888 - 财政年份:
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