Hemodynamic and Metabolic Coupling in Migraine

偏头痛的血流动力学和代谢耦合

• 批准号: 8730250
• 负责人: DAVID DUBOWITZ
• 金额: $ 19.18万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8730250
• 关键词: Address; Adult; Affect; Aftercare; Agonist; Area; Attention; Bed rest; Biological Markers; Biological Neural Networks; Blood Vessels; Caffeine; Carbon Dioxide; Cerebral cortex; Cerebrovascular Circulation; Cerebrum; Chronic; Classification; Common Migraine; Complex; Coupling; Data; Disease; Etiology; Evolution; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Headache; Image; International; Magnetic Resonance Imaging; Measures; Menstrual cycle; Metabolic; Metabolism; Methods; Migraine; Natural History; Nervous system structure; Neurons; Oxygen; Pain; Pathogenesis; Patients; Phase; Physiological; Physiology; Play; Process; Recurrence; Relative (related person); Rest; Risk; Role; Signal Transduction; Spreading Cortical Depression; Stimulus; Stroke; Sumatriptan; Symptoms; Synapses; Techniques; Testing; Time; Tissues; Woman; Work; attenuation; base; blood oxygen level dependent; blood oxygenation level dependent response; clinical application; economic impact; experience; hemodynamics; hypoperfusion; insight; nervous system disorder; neuronal excitability; novel; novel strategies; public health relevance; relating to nervous system; response; tissue oxygenation; tool; visual stimulus

DESCRIPTION (provided by applicant): The long-term goal of these studies is to understand how altered cerebral hemodynamics and oxygen metabolism contribute to neurological disease, and identify their role in the pathophysiology of migraine. Our overall hypothesis is that cerebral blood flow (CBF) and oxygen metabolism (CMRO2) are abnormal in migraine, and this affects local cerebral tissue oxygenation (PtO2). Further, that the CBF / CMRO2 coupling in response to a visual stimulus is also abnormal in migraine. During recent studies we observed hypoperfusion and hypometabolism during migraine without aura, but a greater decline in metabolism resulted in a small increase in local tissue oxygenation during the headache phase. Following sumatriptan both CBF and CMRO2 were normalized. Following a visual stimulus, we observed an increased CBF response, and increased CBF/CMRO2 coupling response, possibly related to neuronal hyperexcitability. Neither of these stimulus-induced changes responded to sumatriptan. Our first specific aim is to characterize the changes in steady-state CBF and CMRO2 during baseline, prodrome symptoms, headache symptoms and in response to sumatriptan, and determine how this affects tissue oxygenation at different phases of migraine. Our second aim is to characterize the CBF/CMRO2 coupling in response to a high contrast vs. a low contrast visual stimulus, again at different phases of migraine. A third aim is to address changes in resting state BOLD synchrony during migraine, as an indication of increased cortical synchrony during migraine. Also to examine a phenomenon of non-aura spreading waves of BOLD signal attenuation, from resting state fMRI data. These studies will be conducted in 10 women with menstrual migraine, and 10 controls. These studies present a new approach to address basic mechanistic questions in migraine pathophysiology. The endpoint of this exploratory work is the characterization of CBF and CMRO2 coupling and its impacts on cerebral tissue oxygenation, as well as the role of BOLD synchrony, during the evolution / treatment of symptoms in menstrual migraine. This will establish the basis for applying these novel MRI tools to evaluate the natural history or response to therapy more widely in migraine disorders.

描述（由申请人提供）：这些研究的长期目标是了解脑血流动力学和氧代谢的改变如何导致神经系统疾病，并确定它们在偏头痛病理生理学中的作用。我们的总体假设是大脑 偏头痛时血流（CBF）和氧代谢（CMRO2）异常，影响局部脑组织氧合（PtO2）。此外，对视觉刺激的 CBF/CMRO2 耦合在偏头痛中也是异常的。在最近的研究中，我们观察到无先兆偏头痛期间存在灌注不足和代谢低下，但代谢的较大下降导致头痛阶段局部组织氧合的小幅增加。服用舒马曲坦后，CBF 和 CMRO2 均正常化。视觉刺激后，我们观察到 CBF 反应增加，CBF/CMRO2 耦合反应增加，可能与神经元过度兴奋有关。这些刺激引起的变化都没有对舒马曲坦产生反应。我们的第一个具体目标是描述基线、前驱症状、头痛症状和舒马曲坦反应期间稳态 CBF 和 CMRO2 的变化，并确定其如何影响偏头痛不同阶段的组织氧合。我们的第二个目标是表征 CBF/CMRO2 耦合对高对比度与低对比度视觉刺激的响应，同样是在偏头痛的不同阶段。第三个目标是解决偏头痛期间静息态 BOLD 同步性的变化，作为偏头痛期间皮质同步性增加的指示。还可以根据静息态 fMRI 数据检查 BOLD 信号衰减的非光环传播波现象。这些研究将在 10 名患有经期偏头痛的女性和 10 名对照者中进行。这些研究提出了解决偏头痛病理生理学基本机制问题的新方法。这项探索性工作的终点是 CBF 和 CMRO2 耦合的特征及其对脑组织氧合的影响，以及 BOLD 同步在月经性偏头痛症状的演变/治疗过程中的作用。这将为应用这些新型 MRI 工具来评估偏头痛疾病的自然史或更广泛的治疗反应奠定基础。