Post-Traumatic Headache (PTH) in Children: Alterations of Brain Function, Blood Flow and Inflammatory Processes

儿童创伤后头痛 (PTH)：脑功能、血流和炎症过程的改变

• 批准号: 9315956
• 负责人: DAVID BORSOOK
• 金额: $ 53.47万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9315956
• 关键词: Accident and Emergency department; Activities of Daily Living; Acute; Age; Anterior; Anxiety; Autonomic Dysfunction; Autonomic nervous system; Awareness; Back; Blood flow; Brain; Brain Concussion; Brain region; Breathing; Cerebrovascular Circulation; Child; Childhood; Chronic; Chronic Brain Damage; Clinic; Clinical Research; Cognition; Cognitive; Craniocerebral Trauma; Data; Diffusion Magnetic Resonance Imaging; Disease; Disease remission; Event; Exercise; Exhibits; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Gene Chips; Headache; Hypothalamic structure; Image; Incidence; Inflammation; Inflammatory; Injury; Insula of Reil; Interleukin-6; Lead; Magnetic Resonance Imaging; Maintenance; Measures; Memory; Migraine; Mild Concussions; Neuraxis; Neuronal Plasticity; Nociception; Outcome Measure; Pain; Patients; Peripheral; Post-Traumatic Headaches; Process; Public Health; Recovery; Reporting; Research; Research Infrastructure; Research Personnel; Resistance; Rest; Risk; Saliva; Sampling; Schools; Series; Severities; Short-Term Memory; Site; Stress; Structure; Suggestion; System; Time; Trigeminal System; aged; brain pathway; cerebrovascular; common symptom; cytokine; experience; experimental study; gray matter; inflammatory marker; insight; mild traumatic brain injury; neuroinflammation; primary outcome; psychologic; public health relevance; response; secondary outcome; sex; trait; white matter

 DESCRIPTION (provided by applicant) Despite increased awareness, a comprehensive understanding of the acute and chronic effects of mTBIs on central nervous system structure and function remains incomplete. Post Traumatic Headache (PTH) is one of the most common symptoms following mTBI and typically develops within 14 days to 3 months after the head injury. PTH incapacitates children in their daily activities (i.e., school, exercise, etc.), and mot importantly, may increase the risk for developing long-term disorders. Although the underlying mechanism remains unknown, PTH may be continuous or evoked/exacerbated by stress (physical or cognitive) indicating that PTH involves multiple brain systems and regions involved in autonomic function. In addition, neuroinflammatory processes may be maintaining/facilitating-sensitized states within these systems. To characterize the autonomic dysfunction in patients with PTH we propose a series of primary and secondary outcomes measures; (Aim 1) To Evaluate brain network alterations in PTH. We hypothesize to find functional and structural alterations in key regions of the autonomic nervous system, which exacerbate PTH. (Aim 2) To Evaluate Alterations in Regional Cerebral Blood Flow (rCBF). We hypothesize that patients with PTH exhibit alterations in basal rCBF and cerebrovascular responses to physical and cognitive stress, suggestive of a dysfunction in autonomic tone. Supporting secondary outcome measures will include; (Aim 3) Autonomic and psychological Markers: To Correlate Alterations in brain function with autonomic and Psychological Markers. We hypothesize that patients with PTH+ exhibit alterations in autonomic tone and psychological trait (anxiety) that contributes to the maintenance of headache related changes and that measures of pain related fear correlate with remission or resistance to headache chronification. (Aim 4) Inflammatory Markers: To Correlate Alterations in brain function and structure (white matter tracts in the brain and trigeminal system with Inflammatory Markers in PTH: We hypothesize that mTBIs induce changes in inflammatory molecules (cytokines) in the periphery (site of head injury) and in the central nervous system and that elevation of pro-inflammatory cytokines (e.g., IL-6) may drive or maintain PTH. Our group has extensive experience in the field of migraine imaging and has the necessary clinical and research personnel, access to patients, and imaging facilities to complete the proposed study.

 描述（由申请人提供）尽管认识有所提高，但对mTBI对中枢神经系统结构和功能的急性和慢性影响的全面理解仍然不完整。创伤后头痛（PTH）是mTBI后最常见的症状之一，通常在头部受伤后14天至3个月内发生。PTH使儿童无法进行日常活动（即，学校、锻炼等），更重要的是，这可能会增加患长期疾病的风险。虽然潜在的机制仍然未知，PTH可能是连续的或诱发/加剧的压力（身体或认知），表明PTH涉及多个大脑系统和区域参与自主功能。此外，神经炎症过程可能在这些系统中维持/促进致敏状态。为了描述PTH患者的自主神经功能障碍，我们提出了一系列主要和次要结局指标：（目的1）评估PTH患者的脑网络改变。我们假设在自主神经系统的关键区域发现了功能和结构的改变，这加剧了PTH。(Aim 2）评价局部脑血流量（rCBF）的变化。我们假设PTH患者表现出基础rCBF和脑血管对身体和认知应激反应的改变，提示自主神经张力功能障碍。支持次要结果的措施将包括;（目标3）自主和心理标记：将大脑功能的改变与自主和心理标记相关联。我们假设，PTH+患者表现出自主神经张力和心理特征（焦虑）的改变，有助于维持头痛相关的变化和疼痛相关的恐惧与缓解或抵抗头痛慢性化的措施。(Aim 4）炎症标志物：将脑功能和结构的改变（脑和三叉神经系统中的白色物质束）与PTH中的炎症标志物相关联：我们假设mTBI诱导外周（头部损伤部位）和中枢神经系统中炎症分子（细胞因子）的变化，并且促炎细胞因子（例如，IL-6）可以驱动或维持PTH。我们的团队在偏头痛成像领域拥有丰富的经验，并拥有必要的临床和研究人员，接触患者和成像设施来完成拟议的研究。