NIBA-TBI: Neuro-Imaging and biofluid-based Biomarker Assessments as translational pathophysiological outcome measures in TBI

NIBA-TBI：神经影像和基于生物流体的生物标志物评估作为 TBI 转化病理生理学结果测量

• 批准号: 10263388
• 负责人: KEVIN Ka Wang WANG
• 金额: $ 39.03万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10263388
• 关键词: Acceleration; Address; Animal Model; Animals; Ballistics; Basic Science; Behavioral; Biological Markers; Blood flow; Brain; Brain Injuries; Brain hemorrhage; Cause of Death; Cells; Clinical; Clinical Management; Clinical Research; Contrast Media; Contusions; Data; Developed Countries; Diffusion Magnetic Resonance Imaging; Dimensions; Drops; Edema; Failure; Fiber; Fibrin fragment D; Fibronectins; Functional Magnetic Resonance Imaging; Future; Gadolinium DTPA; Glial Fibrillary Acidic Protein; Hemorrhage; Histopathology; Human; Image; Injury; Interleukin-6; Investigational Therapies; Knowledge; Lateral; Lesion; Location; Magnetic Resonance Imaging; Measures; Mediating; Modeling; Monitor; Myelin; Myelin Basic Proteins; Necrosis; Nervous System Trauma; Neurofilament-H; Neurofilament-L; Neurons; Outcome; Outcome Measure; Pathologic; Phase; Phase III Clinical Trials; Predisposition; Procedures; Public Health; Rattus; Research; Research Personnel; Resolution; Rest; Rodent; Rodent Model; Sampling; Sequence Analysis; Serum; Severities; Signal Transduction; Site; Spin Labels; Synapses; TNF gene; Testing; Therapeutic; Therapeutic Trials; Thinking; Tissues; Translating; Traumatic Brain Injury; Validation; Vascular Cell Adhesion Molecule-1; Vision; Weight; Work; Yang; axon injury; base; blood oxygen level dependent; candidate marker; clinically relevant; controlled cortical impact; cytokine; disability; efficacy clinical trial; fluid percussion injury; follow-up; functional outcomes; gray matter; in vivo; innovation; interdisciplinary approach; interest; model design; morris water maze; multidisciplinary; necrotic tissue; neuroimaging; neuroimaging marker; neuroinflammation; perfusion imaging; pre-clinical; preservation; success; targeted treatment; tau Proteins; translation to humans; translational model; vascular injury; water diffusion; white matter; white matter injury

PROJECT SUMMARY- ABSTRACT Currently, preclinical TBI research and testing of experimental therapeutic in animal models of TBI models, the most commonly used outcome endpoints are lesion volume/size, neuronal cell preservation and behavioral functional outcome measures (such as Morris water maze, rotarod). While these measures are clearly useful – they lack the ability to inform on the underlying distinct pathophysiological mechanisms relevant in human TBI. These factors might have contributed to the lack of translational success for new TBI therapeutics from animal models efficacy to clinical trial efficacy. Consistent with the vision of the Translational Outcomes Project in Neurotrauma (TOP- NT) (UG3/UH3) RFA, here we carefully assembled a multidisciplinary team and proposed to evaluate two complementary pathological mechanism-based TBI outcome measures – (i) biofluid biomarker assessment, and (ii) MRI-neuroimaging biomarker assessment. These assessments are chosen because they are both highly quantitative and can readily transition into clinical TBI studies and future therapeutic trials. Our central hypothesis is as follows: In preclinical multi-site multi-TBI animal model setting, biofluid-based biomarker and quantitative MRI-based neuroimaging biomarker assessment can be developed into useful translational outcome measures that can help address a range of clinical TBI pathological mechanistic subphenotypes including axonal injury, contusion/tissue necrosis, loss of synaptic continuity, white matter injury, microvascular injury/brain hemorrhage and neuroinflammation. We have also put together a “Clinical TBI Translational Advisory” panel to assist us with translating our findings into clinical studies.

项目摘要-摘要 目前，临床前TBI研究和动物实验治疗的测试 TBI模型中，最常用的结局终点是病变 体积/大小、神经元细胞保存和行为功能结局指标 (such如Morris水迷宫、旋转棒）。虽然这些措施显然是有用的， 缺乏了解潜在的不同病理生理机制的能力 与人类TBI有关。这些因素可能导致缺乏翻译 从动物模型疗效到临床试验疗效，新的TBI疗法取得了成功。 与神经创伤转化成果项目（TOP- NT）（UG 3/UH 3）RFA，在这里，我们精心组建了一个多学科团队， 建议评价两种互补的基于病理机制的TBI结局 测量-（i）生物流体生物标志物评估，和（ii）MRI-神经成像生物标志物 考核之所以选择这些评估，是因为它们都是高度量化的 并且可以容易地过渡到临床TBI研究和未来的治疗试验。我们 中心假设如下：在临床前多部位多TBI动物模型设置中， 基于生物流体的生物标志物和基于定量MRI的神经成像生物标志物 评估可以发展成有用的转化结果测量， 解决了一系列临床TBI病理机制亚表型，包括轴突 损伤、挫伤/组织坏死、突触连续性丧失、白色物质损伤， 微血管损伤/脑出血和神经炎症。我们还把 我们还成立了一个“临床TBI翻译咨询”小组，帮助我们翻译我们的 临床研究的发现。