NEURAL SITES MEDIATING OBSTGRUCTIVE SLEEP APNEA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。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。我们先前已经证明，阻塞性睡眠呼吸暂停和心力衰竭患者在小脑、边缘和皮质区域表现出显著的灰质丢失，这些灰质参与调节呼吸模式、停顿后开始呼吸、上呼吸道肌肉组织的精细控制和血压。通过功能磁共振成像(FMRI)，我们还发现，在与灰质丢失区域重叠的大脑区域，对呼吸和心血管挑战产生异常的神经反应。OSA中一些结构和功能异常的区域接受轴突投射，这些轴突对低氧血症和兴奋性毒性特别敏感，这表明某些异常可能是反复低氧发作的结果。其他灰质丢失或功能障碍的大脑部位是单侧的，或者位于对低氧血症不那么敏感的灌注区，这表明该综合征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来a)显示Olivo-Purkinje攀登纤维的轴突损伤和通向海马CA1区的穿支路径纤维，以及b)确定海马区、小脑皮质和深核、岛叶、额叶和顶叶皮质灰质丢失的特定区域。功能磁共振成像将被用来评估受影响区域在更高的空间和时间分辨率下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张力、呼吸动作不同步和与睡眠中呼吸紊乱相关的高交感神经张力的致命性神经缺陷。确定睡眠期间反复缺氧导致的轴突和灰质丢失是治疗干预发展的重要和必要的一步。

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.