Trigeminovascular sensitization in post-traumatic headache: electrophysiologic and blood biomarkers in youth

创伤后头痛中的三叉血管敏化：青少年的电生理学和血液生物标志物

• 批准号: 10349936
• 负责人: Carlyn Anne Patterson Gentile
• 金额: $ 18.31万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10349936
• 关键词: Adult; Affect; Age; Animal Model; Biological Markers; Biological Process; Blood; Brain Concussion; Brain Stem; Calcitonin Gene-Related Peptide; Caring; Child; Childhood; Chronic; Clinical; Clinical Research; Clinical Trials; Data; Development; Doctor of Philosophy; Electrophysiology (science); Enrollment; Environment; Functional disorder; Future; Goals; Grant; Guidelines; Headache; Headache Disorders; Health; Hour; Individual; Inflammatory; Infrastructure; Interleukin-6; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Migraine; Mind; Neurons; Neurosciences; Participant; Pathogenesis; Pathway interactions; Patients; Pediatric Hospitals; Pennsylvania; Peripheral; Persons; Philadelphia; Photophobia; Physicians; Play; Positioning Attribute; Post-Traumatic Headaches; Principal Component Analysis; Prognostic Marker; Property; Recommendation; Recovery; Reporting; Research; Research Design; Research Infrastructure; Research Personnel; Resolution; Risk; Role; Scientist; Signal Transduction; Specialist; Symptoms; System; TNF gene; Techniques; Testing; Time; Training; Traumatic Brain Injury; Trigeminal Nuclei; Trigeminal System; United States; Universities; Vision; Visual; Visual Cortex; Visual evoked cortical potential; Visual system structure; Youth; biomarker development; candidate marker; career development; clinical candidate; clinical infrastructure; common symptom; cytokine; disability; disabling symptom; early detection biomarkers; experience; frontier; improved; novel; peripheral blood; predictive marker; programs; prophylactic; recruit; signal processing; skills

PROJECT SUMMARY/ABSTRACT Candidate: I am a headache specialist at the Children’s Hospital of Philadelphia (CHOP). I have a PhD in visual systems neuroscience that focused on studying properties of neuronal adaptation in the visual cortex. More recently, I have begun clinical research related to pediatric headache disorders and the study of photophobia in migraine. My long-term goal is to elucidate the pathophysiology of concussion and headache, identify relevant biomarkers, and improve the treatment of these conditions in young people. This grant will enable me to build skills in concussion biomarker development to become an independent, translational neuroscientist dedicated to improving the care of concussion and headache in children. Research: Concussion is a major health concern, affecting 20% of youth in the United States. Headache is the most common symptom following concussion and is associated with longer recovery times and greater disability. However, there are no accepted guidelines on how or when to treat post-traumatic headache (PTH), and there are no early biomarkers to identify youth at risk for prolonged PTH. PTH and migraine share many clinical features and may have overlapping pathophysiology. The goal of this proposal is to determine if pathophysiologic substrates of migraine are present early in PTH. I will examine electrophysiologic and blood candidate biomarkers associated with trigeminovascular pathway sensitization (central to migraine pathogenesis) at multiple time points in youth with PTH lasting longer than 1 month. These measures will be compared to youth with symptom resolution. Environment and Career Development: CHOP and University of Pennsylvania (Penn) offer a rich environment for me to develop as an independent investigator. My mentorship team has diverse expertise and will provide me with a unique set of skills to support biomarker development in pediatric concussion. My primary mentor, Dr. Geoffrey K Aguirre, is an accomplished vision neuroscientist with expertise in the visual system in migraine. He will provide the mentorship needed to develop advanced techniques in signal processing for electrophysiologic biomarkers. My co-mentor, Dr. Ramon Diaz-Arrastia, is a leader in traumatic brain injury biomarker research. He will provide guidance and support on study design for blood biomarker development including the use of biomarkers in clinical trials. My second co-mentor, Dr. Christina Master, is an expert in pediatric concussion who has built the Frontier Minds Matter concussion program at CHOP. This program provides an extensive and well-integrated clinical and research infrastructure for longitudinal concussion studies in youth, which will provide crucial support to the proposed studies.

项目总结/摘要 应聘者：我是费城儿童医院的头痛专家。我有博士学位 视觉系统神经科学，专注于研究视觉皮层中神经元适应的特性。 最近，我开始了与儿童头痛疾病相关的临床研究， 偏头痛中的恐惧症。我的长期目标是阐明脑震荡和头痛的病理生理学， 确定相关的生物标志物，并改善对年轻人这些疾病的治疗。这笔赠款将 使我能够建立脑震荡生物标志物开发的技能，成为一个独立的，翻译 神经科学家致力于改善儿童脑震荡和头痛的护理。 研究：脑震荡是一个主要的健康问题，影响了美国20%的青少年。头疼的是 脑震荡后最常见的症状，并与较长的恢复时间和更大的 残疾。然而，关于如何或何时治疗创伤后头痛（PTH）， 并且没有早期的生物标志物来识别有延长PTH风险的年轻人。甲状旁腺激素和偏头痛 临床特征和可能有重叠的病理生理学。本提案的目的是确定， 偏头痛的病理生理学底物在PTH中存在较早。我会检查电生理和血液 与三叉神经血管通路致敏（偏头痛中枢）相关的候选生物标志物 发病机制）在多个时间点与PTH持续时间超过1个月的青年。这些措施将 与症状缓解的年轻人相比。 环境和职业发展：CHOP和宾夕法尼亚大学（Penn）提供丰富的 环境，让我成为一名独立的调查员。我的导师团队拥有不同的专业知识， 将为我提供一套独特的技能，以支持儿科脑震荡生物标志物的发展。我 主要导师Geoffrey K Aguirre博士是一位有成就的视觉神经科学家，在视觉神经科学方面具有专业知识。 偏头痛的系统他将提供发展信号领域先进技术所需的指导 用于电生理学生物标记的处理。我的共同导师Ramon Diaz-Arrastia博士是创伤治疗领域的领导者 脑损伤生物标志物研究。他将为血液生物标志物的研究设计提供指导和支持 开发，包括在临床试验中使用生物标志物。我的第二位导师克里斯蒂娜·马斯特博士是一位 儿童脑震荡专家，他在CHOP建立了前沿脑震荡项目。这 该计划提供了一个广泛的和良好的综合临床和研究基础设施，为纵向 青年脑震荡研究，这将为拟议的研究提供重要支持。