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的临床前研究和实验性治疗性TBI动物模型的测试