Brain Axonal Injury in Obstructive Sleep Apnea

阻塞性睡眠呼吸暂停引起的脑轴突损伤

• 批准号: 8692590
• 负责人: Rajesh Kumar
• 金额: $ 33.96万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8692590
• 关键词: Acute; Adult; Affect; Age; American; Anisotropy; Anxiety; Area; Arrhythmia; Axon; Bilateral; Brain; Cardiovascular system; Cells; Characteristics; Chronic; Cognitive deficits; Comorbidity; Corpus Callosum; Data; Development; Diagnosis; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Dorsal; Early Intervention; Edema; Emotional; Evaluation; External Capsule; Fiber; Gender; Healthcare; Hippocampus (Brain); Hypertension; Hypoxia; Image; Imaging Techniques; Incidence; Infarction; Injury; Intervention; Length; Magnetic Resonance Imaging; Measures; Memory; Metabolic; Moods; Myelin; Nature; Neuropsychology; Newly Diagnosed; Obesity; Obstructive Sleep Apnea; Pathological Staging; Pathology; Patients; Perfusion; Physiological; Population; Postmenopause; Procedures; Process; Radial; Recovery; Rehabilitation therapy; Rest; Severities; Site; Source; Staging; Stroke; Structure; Syndrome; Techniques; Tissues; Treatment Protocols; Water; Woman; base; brain volume; cytotoxic; gray matter; indexing; injured; insight; male; neuroprotection; neuropsychological; prevent; relating to nervous system; stem; water diffusion; white matter; white matter change; white matter injury

DESCRIPTION (provided by applicant): The objective is to determine whether the white matter injury in obstructive sleep apnea (OSA) results from myelin or axonal damage, and whether those changes are in acute or chronic stages. OSA is a common and progressive syndrome accompanied by severe cardiovascular, metabolic, memory, emotional, and cognitive deficits, presumably stemming from compromised neural processes induced by intermittent hypoxia and perfusion changes accompanying the condition. The need to determine myelin vs axonal injury rests with interventions for neuroprotection to prevent further injury; specific treatment protocols exist for myelin vs axonal protection. We also need to know whether these fiber changes are recent, or have been in place for long periods, an insight necessary for potential recovery by ventilatory-only support procedures, rather than neural protection intervention. Both gray and white matter tissues are affected in OSA; however, the nature of the white matter changes which interconnect gray matter structures is unknown. We will assess whether the changes in white matter over the entire brain are in acute or chronic stages, and whether regional fibers are showing changes in myelin or axons. We will also assess fiber characteristics of selected fiber bundles which, from evidence of others, are known to contribute to cardiovascular, memory and affect deficits prominent in OSA. Studies will use recently-diagnosed, treatment naive, moderate-to-severe OSA subjects and age- and gender-matched control subjects. The pathological stage of white matter injury will be examined by diffusion tensor imaging (DTI) and diffusional kurtosis imaging (DKI)-based mean diffusivity and mean kurtosis indices. Myelin vs axonal changes will be assessed by DTI and DKI-based axial diffusivity and axial kurtosis, and radial diffusivity and radial kurtosis measures, which show axonal and myelin changes, respectively. We will use both DTI and DKI techniques, since each procedure offers unique advantages. More detailed myelin evaluation will be performed by magnetization transfer imaging (MTI) procedures. Finally the number of fibers, mean length, and other fiber characteristics will be evaluated by fiber tractography. Our preliminary data suggest that the white matter injury in OSA principally is in an early stage, and largely arise from changes in myelin, although axonal changes also appeared in particular sites in newly-diagnosed patients. The cardiovascular and neuropsychological sequelae of OSA are severe, and are prominent in targets for the condition, obese, older males and post-menopausal women. Protection against the neural changes underlying the pathologies would significantly contribute to national health care. These studies have the potential to determine white matter pathological changes in OSA, and thus point to interventions most appropriate for neural protection and recovery in the syndrome.]

描述（由申请人提供）：目的是确定阻塞性睡眠呼吸暂停（OSA）中的白色损伤是否由髓鞘或轴突损伤引起，以及这些变化是否处于急性或慢性阶段。OSA是一种常见的进行性综合征，伴有严重的心血管、代谢、记忆、情感和认知缺陷，可能源于伴随该病症的间歇性缺氧和灌注变化诱导的受损神经过程。确定髓鞘与轴突损伤的需要取决于神经保护的干预措施，以防止进一步的损伤;存在髓鞘与轴突保护的特定治疗方案。我们还需要知道这些纤维变化是最近发生的，还是已经发生了很长一段时间，这是通过仅通气支持程序而不是神经保护干预进行潜在恢复所必需的。在OSA中，灰质和白色物质组织都受到影响;然而，与灰质结构互连的白色物质变化的性质尚不清楚。我们将评估整个大脑的白色物质的变化是处于急性还是慢性阶段，以及区域纤维是否显示髓鞘或轴突的变化。我们还将评估所选纤维束的纤维特征，从其他证据来看，已知这些纤维束有助于OSA中突出的心血管、记忆和影响缺陷。研究将使用最近诊断的、未经治疗的、中度至重度OSA受试者和年龄和性别匹配的对照受试者。白色损伤的病理阶段将通过基于平均扩散率和平均峰度指数的扩散张量成像（DTI）和扩散峰度成像（DKI）进行检查。将通过基于DTI和DKI的轴向扩散率和轴向峰度以及径向扩散率和径向峰度测量（分别显示轴突和髓鞘变化）评估髓鞘与轴突变化。我们将同时使用DTI和DKI技术，因为每种方法都有独特的优势。将通过磁化传递成像（MTI）程序进行更详细的髓鞘评估。最后，纤维束的数量，平均长度，和其他纤维特性将通过纤维追踪图进行评估。我们的初步数据表明，白色物质的损害主要是在早期阶段，并在很大程度上引起髓鞘的变化，虽然轴突的变化也出现在特定的网站在新诊断的患者。OSA的心血管和神经心理学后遗症是严重的，并且在肥胖、老年男性和绝经后女性的目标中是突出的。防止病理学背后的神经变化将大大有助于国家卫生保健。这些研究有可能确定OSA中的白色物质病理变化，从而指出最适合于该综合征中神经保护和恢复的干预措施。