Neural Sites Mediating Obstructive Sleep Apnea

调节阻塞性睡眠呼吸暂停的神经部位

• 批准号: 6741089
• 负责人: RONALD Marven HARPER
• 金额: $ 19.97万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6741089
• 关键词: bioimaging /biomedical imaging; blood flow measurement; brain imaging /visualization /scanning; brain mapping; cerebellar Purkinje cell; cerebellar cortex; clinical research; electrocardiography; electroencephalography; frontal lobe /cortex; functional magnetic resonance imaging; hippocampus; human subject; hypoxia; neuroanatomy; oximetry; pulmonary respiration; respiratory airflow disorder; sleep apnea

The project will investigate the structural and functional neuroanatomy of sleep disordered breathing associated with obstructive sleep apnea (OSA), a syndrome that affects up to 4 % of the population. Our studies in the past period demonstrated that OSA and heart failure patients show significant gray matter loss in cerebellar, limbic, and cortical areas that mediate patterning of breathing, initiation of respiration following a pause, fine control of upper airway musculature, and blood pressure. With functional magnetic resonance imaging (tMRI), we also found abnormal neural responses develop to breathing and cardiovascular challenges in brain regions that overlap areas of gray matter loss. Some of the regions that showed structural and functional abnormalities in OSA receive axonal projections that are extraordinarily sensitive to hypoxemia and excitotoxicity, suggesting that certain abnormalities may resuk from repeated hypoxic episodes. Other brain sites with gray matter loss or dysfunction were unilateral or were in well-perfused areas that are less sensitive to hypoxemia, suggesting the possibility of maldevelopment or neural damage pre-existing the syndrome. We will use high resolution volumetric structural MRI and diffusion tensor MRI in OSA patients and controls to a) demonstrate axonal damage in olivo-Purkinje climbing fibers of the cerebellum and perforant path fibers to the CA1 region of the hippocampus, and b) define specific areas of gray matter loss in hippocampal, cerebellar cortex and deep nuclei, and insular, frontal and parietal cortex. Functional MRI will be used to evaluate neural responses in affected areas to a cold pressor challenge at higher spatial and temporal resolution. The studies have the potential to reveal the causative neural deficits that lead to the upper airway atonia, out-of-synchrony respiratory action, and high sympathetic tone associated with disordered breathing during sleep. The determination of axonal and gray matter loss resulting from repeated hypoxia during sleep represents a significant and necessary forward step in the development of therapeutic interventions.

该项目将调查与阻塞性睡眠呼吸暂停（OSA）相关的睡眠呼吸障碍的结构和功能神经解剖学，OSA是一种影响高达4%人口的综合征。我们过去的研究表明，阻塞性睡眠呼吸暂停和心力衰竭患者的小脑、边缘系统和皮质区域显示出显著的灰质损失，这些区域介导呼吸模式、暂停后的呼吸启动、上气道肌肉组织的精细控制和血压。通过功能性磁共振成像（tMRI），我们还发现在与灰质损失区域重叠的大脑区域中，呼吸和心血管挑战会产生异常的神经反应。在OSA中显示出结构和功能异常的一些区域接收对低氧血症和兴奋性毒性异常敏感的轴突投射，这表明某些异常可能是由反复的低氧发作引起的。其他有灰质丢失或功能障碍的脑部位是单侧的，或者是在对低氧血症不太敏感的灌注良好的区域，这表明有可能是 发育不良或神经损伤预先存在的综合征。我们将在OSA患者和对照组中使用高分辨率体积结构MRI和扩散张量MRI，以a）证明小脑橄榄-浦肯野攀爬纤维和海马CA 1区穿通路径纤维中的轴突损伤，以及B）定义海马、小脑皮质和深核以及岛叶、额叶和顶叶皮质中灰质丢失的特定区域。功能性MRI将用于以更高的空间和时间分辨率评价受影响区域对冷加压挑战的神经反应。这些研究有可能揭示致病的神经 这些缺陷导致上呼吸道弛缓、不同步的呼吸动作以及与睡眠期间呼吸紊乱相关的高交感神经紧张。确定睡眠期间反复缺氧导致的轴突和灰质损失代表了治疗干预发展中重要且必要的前进步骤。