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（由适用提供）尽管有提高意识，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了解仍然不完整。创伤后头痛（PTH）是MTBI后最常见的症状之一，通常在头部受伤后的14天到3个月内发育。 PTH无能为力，可以使儿童在日常活动（即学校，运动等）中，并且重要的是，可能会增加患上长期疾病的风险。尽管基本机制仍然未知，但PTH可能会因压力（物理或认知）而连续或诱发/加剧，表明PTH涉及多个大脑系统和参与自主功能的区域。此外，神经炎症过程可能在这些系统中维持/促进对敏感的状态。为了表征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果措施。 （目标1）评估PTH中的大脑网络变化。我们假设在自主神经系统的关键区域中发现功能和结构改变，这加剧了PTH。 （目标2）评估区域脑血流（RCBF）的改变。我们假设患有PTH的患者在基本RCBF和对身体和认知胁迫的脑血管反应中发生了改变，这表明自主性语调功能障碍。支持次要结果指标将包括； （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+暴露于自主语调和心理性状（焦虑）的患者有助于维持与标头相关的变化，并且测量与疼痛相关的恐惧的测量与缓解或抵抗力相关。 （目标4）炎症标记：与脑功能和结构的改变相关（脑和三一致性标记中的白质和PTH中的炎症标记：我们假设MTBIS MTBIS炎症分子（细胞因子（细胞因子）诱导周围神经损伤的位点）和中央神经系统的驱动器和cy-efation-efation-efation-efation-efation-efation-efation cy nimins cyt（e）（e）（e e cy nimin cy nimins cyt of intermines）cytim cy nimins cyt（cy）。保持PTH。