Sex differences in traumatic brain injury: Neural circuit mediators of overlapping stress and physical effects

创伤性脑损伤的性别差异：重叠压力和物理效应的神经回路调节因素

• 批准号: 10751089
• 负责人: Megan E Huibregtse
• 金额: $ 7.61万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-14 至 2025-07-13
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10751089
• 关键词: Accident and Emergency department; Acute; Address; Affect; American; Animals; Antiinflammatory Effect; Astrocytes; Attention; Award; Axon; Biometry; Blood specimen; Brain; Brain Concussion; Brain Injuries; Chronic Post Traumatic Stress Disorder; Chronic stress; Complex; Congresses; Consensus; Craniocerebral Trauma; DSM-V; Data; Data Reporting; Data Science; Data Set; Diagnosis; Diffusion Magnetic Resonance Imaging; Dimensions; Discipline; Estradiol; Exhibits; Extinction; Female; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Glial Fibrillary Acidic Protein; Goals; Head; Headache; Health Surveys; Hormonal; Hormones; Hour; Human; Impairment; Individual; Injury; Intermediate Filament Proteins; Intervention; Investigation; Knowledge; Life; Light; Literature; Longitudinal Studies; Masks; Measures; Mechanics; Mediating; Mediator; Menstrual cycle; Mental Depression; Mental Health; Mentors; Military Personnel; Neurobiology; Neuroendocrinology; Neurosciences Research; Outcome; Participant; Patient Recruitments; Patient Self-Report; Patients; Perimenopause; Persons; Physical Medicine; Population; Post-Traumatic Stress Disorders; Predisposition; Prevalence; Psychopathology; Qualifying; Quality of life; Questionnaires; Reporting; Research; Research Personnel; Rest; Risk; Risk Factors; Role; Sampling; Sex Differences; Signs and Symptoms; Site; Sports; Stress; Symptoms; TBI Patients; Time; Training; Trauma; Traumatic Brain Injury; United States; Vehicle crash; Visual; Woman; acute stress; associated symptom; biological adaptation to stress; career; cohort; decrease resilience; depressive symptoms; experience; falls; female sex hormone; health disparity; health related quality of life; intimate partner violence; male; medical attention; member; men; mental state; mild traumatic brain injury; neural circuit; neural correlate; neuroimaging; neuroimaging marker; neuroprotection; neuropsychiatry; neurosteroids; new therapeutic target; novel; physical assault; post-doctoral training; post-trauma; pre-clinical research; psychosocial stressors; recruit; reproductive; response; sex; sexual assault; tool; trauma exposure; traumatic event; violence against women; white matter

PROJECT SUMMARY Women experience worse symptoms and outcomes following traumatic brain injury (TBI), contrary to the consensus in preclinical research that female sex hormones confer neuroprotection. Multiple mechanisms have been proposed to drive this health disparity, including hormonal fluctuations during the menstrual cycle and into the menopausal transition, a predisposition to seek medical attention or report symptoms, and increased neurobiological vulnerability to injury. In particular, increased vulnerability to mechanical trauma in female axons and the role of neurosteroid hormones have not been thoroughly examined in human TBI. While mild traumatic brain injuries (mTBI) make up the majority of TBIs, research often focuses on a specific sub-type of mTBI: sports-related concussions. However, many people experience head trauma during a traumatic event, such as motor vehicle collisions, physical assault, sexual assault, or falls, and the lifetime prevalence of experiencing at least traumatic event is extremely high (90%). As the literature on sports-related concussions may not always generalize to this trauma-exposed population, we aim to characterize sex differences in structural and functional connectivity (Aim 1), examine sex-dependent associations between TBI pathophysiology and outcomes (Aim 2), and finally assess the influence of concurrent estradiol levels on TBI outcomes and neuroimaging markers (Aim 3) To address these aims, I will leverage a large, existing dataset from the AURORA study, a multisite, longitudinal study of posttraumatic outcomes. Participants were recruited to AURORA if they presented to a participating Emergency Department (ED) within 72 hours of a qualifying traumatic event and then were followed through 12-months posttrauma. Participants were assessed using a multidimensional range of tools and measures to general a one-of-a-kind, rich dataset to study the complex, co-occurring symptoms and overlapping neural correlates of adverse posttraumatic neuropsychiatric sequelae across a variety of disciplines. About one-third of AURORA participants met modified American Congress of Rehabilitation Medicine criteria for TBI. However, as the acute and chronic stress responses can mask and compound signs and symptoms of TBI, it is essential to use an objective marker to establish TBI in this trauma- exposed cohort. We propose to use ED GFAP levels to identify individuals with TBI, which have shown to be significantly elevated in individuals with TBI for several days following presentation at the ED. TBI outcomes will include not only somatic symptoms (e.g., headache, sensitivity to light) but also PTSD and depression symptoms and mental health-related quality of life. Completion of this project will not only inform our understanding of neurobiological factors that affect sex differences in TBI outcomes but also provide excellent postdoctoral training for the applicant in diffusion magnetic resonance imaging, resting-state functional connectivity, neuroendocrinology, PTSD and stress-related psychopathology, and biostatistics and data science for human neuroscience research, preparing her for a successful career as an independent scholar.

项目摘要 妇女经历了脑损伤（TBI）后的症状和结局较差，与之相反 在临床前研究中，女性性激素赋予神经保护作用。多种机制 已提出提出这种健康差异，包括月经周期中的激素波动 并进入更年期过渡，寻求医疗护理或报告症状的倾向，以及 神经生物学脆弱性增加。特别是，增加了机械创伤的脆弱性 在人类TBI中尚未彻底检查雌性轴突和神经素激素的作用。 虽然轻度创伤性脑损伤（MTBI）构成了大多数TBI，但研究通常集中于特定 MTBI的子类型：与运动有关的脑震荡。但是，许多人在 创伤事件，例如机动车碰撞，身体攻击，性侵犯或跌倒，以及一生 至少经历创伤事件的患病率极高（90％）。作为与体育有关的文献 脑震荡可能并不总是概括为暴露于创伤的人群，我们旨在表征性别 结构和功能连通性的差异（AIM 1），检查TBI之间的性别依赖性关联 病理生理学和结果（AIM 2），最后评估并发雌二醇对TBI的影响 结果和神经影像标记（AIM 3）以解决这些目标，我将利用一个大型的现有数据集 根据Aurora研究，这是一项多站点的创伤后结局的纵向研究。参与者被招募 如果他们在合格的72小时内向参与的急诊室（ED）提交给Aurora 创伤事件，然后在创伤后12个月内进行。使用A评估参与者 多维工具和措施，用于一般一个独一无二，丰富的数据集，以研究复合物， 不良创伤后神经精神后遗症的同时出现症状和重叠的神经相关性 跨越各种学科。大约三分之一的Aurora参与者会见了经过改装的美国国会 TBI的康复医学标准。但是，由于急性和慢性压力反应可以掩盖，并且 TBI的化合物体征和症状，必须使用客观标记在这种创伤中建立TBI 裸露的队列。我们建议使用ED GFAP级别识别具有TBI的人，这些人已证明是 在ED介绍后的几天内，TBI的个体中有显着升高。 TBI结果 将不仅包括躯体症状（例如头痛，对光的敏感性），还包括PTSD和抑郁症 症状和与心理健康相关的生活质量。该项目的完成不仅会告知我们 了解影响TBI结果差异但也提供出色的神经生物学因素 扩散磁共振成像中申请人的博士后训练，静止状态功能 连通性，神经内分泌学，PTSD和与压力有关的心理病理学以及生物统计学和数据 人类神经科学研究科学，为她做好准备，以成功地成为独立学者。