NEURAL SITES MEDIATING OBSTGRUCTIVE SLEEP APNEA

调节阻塞性睡眠呼吸暂停的神经部位

• 批准号: 7369437
• 负责人: RONALD Marven HARPER
• 金额: $ 1.02万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7369437
• 关键词: NEURAL; SITES; MEDIATING; OBSTGRUCTIVE; SLEEP

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The project investigates 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. We have previously 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 (fMRI), 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 result 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.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。该项目调查了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。我们以前已经证明，阻塞性睡眠呼吸暂停和心力衰竭患者在小脑、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、暂停后呼吸的启动、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（fMRI），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大脑部位是单侧的，或者是在对低氧血症不太敏感的灌注良好的区域，这表明可能存在发育不良或神经损伤的可能性。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导致上呼吸道弛缓、不同步呼吸动作和与睡眠呼吸障碍相关的高交感神经张力的致病性神经缺陷。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。