Identifying Biomarkers that Modify Outcomes in Soccer Heading

识别改变足球标题结果的生物标志物

• 批准号: 9332608
• 负责人: Liane Elizabeth Hunter
• 金额: $ 4.4万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE, INC
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-21 至 2020-03-20
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9332608
• 关键词: Alleles; Alzheimer' s Disease; Apolipoprotein E; Attenuated; Basic Science; Biological Markers; Brain; Brain Concussion; Brain Injuries; Brain-Derived Neurotrophic Factor; Characteristics; Clinical; Clinical Investigator; Clinical Research; Cognition; Cognitive; Cohort Studies; Craniocerebral Trauma; Deterioration; Development; Diffusion Magnetic Resonance Imaging; Exercise; Fostering; Foundations; Functional disorder; Genes; Genetic Polymorphism; Goals; Guidelines; Head; Heterogeneity; Impaired cognition; Impairment; Individual; Inflammatory; Injury; Interleukin-1 beta; Interleukin-6; Laboratories; Magnetic Resonance Imaging; Memory impairment; Mentorship; Modality; Nerve Degeneration; Neurodegenerative Disorders; New York City; Outcome; Pathologic; Pathology; Patient Outcomes Assessments; Patients; Performance; Play; Process; Proteins; Reporting; Research; Research Methodology; Research Personnel; Risk; Role; Single Nucleotide Polymorphism; Soccer; Sports; Synaptic plasticity; TNF gene; Techniques; Time; Tissues; Training; Traumatic Brain Injury; Uncertainty; United States; Valine; Work; adverse outcome; apolipoprotein E-4; axon injury; base; biological adaptation to stress; cognitive performance; cytokine; gene interaction; memory process; mild traumatic brain injury; neurogenesis; neuroinflammation; neurotrophic factor; neurotropic; normal aging; processing speed; public health intervention; response; sterol esterase; trait; young adult

Abstract The effects of repetitive heading in soccer, outside the purview of recognized concussion, are a topic of major public importance that has not been well defined. Recent work from our laboratory has shown that repetitive sub-concussive soccer heading is associated with evidence of microstructural tissue damage as well as cognitive impairments. We have found that there exists a threshold number of heads per year whereby subclinical and clinical impairments are evident. Despite this evidence of axonal and functional damage, we have not characterized individuals at greater and/or reduced risk for deterioration from repetitive soccer heading. In this proposed study we will investigate trait biomarkers hypothesized to have an association with neurodegenerative processes subsequent to brain injury. Specifically, we will examine the effect-modifying role of the Apolipoprotein E, Cholesterol Esterase Transfer Protein and Brain Derived Neurotrophic Factor polymorphisms. Furthermore, we will explore the extent to which the ex-vivo inflammatory stress response can explain the heterogeneity in outcomes. Under the mentorship of Dr. Michael Lipton and investigators with varying expertise pertaining to the project, I am confident that I will accomplish my goal of identifying biomarkers that confer greater vulnerability to heading related impairments. Furthermore, I will receive excellent training in clinical research methods and basic science techniques alike, which will serve as an excellent foundation for my ultimate goal of becoming an independent clinical Investigator.

摘要 足球中重复头球的影响，在公认的脑震荡的范围之外，是一个主题 尚未很好定义的重大公众重要性。我们实验室最近的工作表明 重复的亚脑震荡足球头球与微结构组织的证据有关 损害以及认知障碍。我们发现，存在一个阈值数量 亚临床和临床损害是明显的。尽管有这些证据表明 轴突和功能损害，我们没有描述个体有更大和/或更低的风险 由于重复的足球头球而恶化。在这项拟议的研究中，我们将研究性状生物标记物 被认为与脑损伤后的神经退化过程有关。 具体地说，我们将研究载脂蛋白E，胆固醇酯酶的效果调节作用 转移蛋白和脑源性神经营养因子基因多态性。此外，我们还将探索 体外炎症应激反应能在多大程度上解释 结果。在迈克尔·利普顿博士和具有不同专业知识的调查人员的指导下 关于这个项目，我有信心我将完成我的目标，识别生物标记物 使其更容易受到与航向有关的损伤。此外，我还会得到很好的训练 在临床研究方法和基础科学技术方面，这将是一个优秀的 为我成为一名独立的临床研究员的最终目标奠定了基础。