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

项目摘要/摘要 候选人：我是费城儿童医院(CHOP)的头痛专家。我有一个博士学位 视觉系统神经科学，专注于研究视觉皮质中神经元适应的特性。 最近，我开始了与儿童头痛障碍相关的临床研究，以及对 偏头痛的畏光症状。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，并改进年轻人对这些疾病的治疗。这笔赠款将 使我能够培养脑震荡生物标志物开发方面的技能，成为独立的、翻译的 神经学家，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%的年轻人。头疼的是 脑震荡后最常见的症状，与较长的恢复时间和更大的 残疾。然而，对于如何或何时治疗创伤后头痛(PTH)，目前还没有公认的指南。 而且，目前还没有早期的生物标志物来识别青少年甲状旁腺激素延长的风险。甲状旁腺激素和偏头痛有许多共同之处 临床特征，可能有重叠的病理生理学。这项提案的目标是确定是否 偏头痛的病理生理基础在甲状旁腺功能亢进症早期出现。我会检查电生理和血液 与三叉神经血管通路敏化相关的候选生物标记物(偏头痛的中枢 发病机制)，在多个时间点的青年甲状旁腺激素持续超过1个月。这些措施将是 与症状解决的年轻人相比。 环境和职业发展：CHOP和宾夕法尼亚大学(宾夕法尼亚大学)提供丰富的 为我发展成为一名独立调查员提供了良好的环境。我的指导团队拥有不同的专业知识和 将为我提供一套独特的技能来支持儿科脑震荡生物标记物的开发。我的 首席导师杰弗里·K·阿吉雷博士是一位成就卓著的视觉神经学家，在视觉方面拥有专业知识。 偏头痛的系统。他将提供所需的指导，以发展先进的信号技术 电生理生物标志物的加工。我的另一位导师拉蒙·迪亚兹-阿拉斯蒂亚医生是创伤科的领导者 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 发展，包括在临床试验中使用生物标记物。我的第二位导师克里斯蒂娜·马斯特博士是一位 儿科脑震荡专家，在CHOP建立了前沿意识脑震荡项目。这 计划提供广泛且集成良好的临床和研究基础设施 青年脑震荡研究，这将为拟议的研究提供关键支持。

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.