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: 10242480
• 负责人: KEVIN Ka Wang WANG
• 金额: $ 39.64万
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10242480
• 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; 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

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.

目前，TBI动物模型中的临床前TBI研究和实验疗法测试 模型，最常用的结果终点是病变体积/大小，神经元细胞保存 和行为功能结果指标（例如莫里斯水迷宫，rotarod）。而这些 措施显然是有用的 - 他们缺乏告知基本不同的能力 与人类TBI相关的病理生理机制。这些因素可能有助于 从动物模型有效性到临床的新TBI治疗缺乏转化成功 试用效率。与Neurotrauma转化结果项目的愿景一致 （top-nt）（ug3/uh3）RFA，在这里，我们仔细组装了一个多学科团队，并提议 评估两种基于病理机制的TBI结果指标 - （i）生物流体 生物标志物评估和（ii）MRI NEUROIMATIGGING生物标志物评估。选择这些评估 因为它们都是高度定量的，并且可以轻易地转变为临床TBI研究，并且 未来的热试验。我们的中心假设如下：在临床前多站点中 多-TBI动物模型设置，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为有用的转化结果指标，可以帮助 介绍一系列TBI病理机械性亚表征，包括轴突损伤， 挫伤/组织坏死，突触连续性丧失，白质损伤，微血管 损伤/脑出血和神经​​炎症。我们还整理了“临床TBI 翻译咨询”小组，以帮助我们将发现转化为临床研究。