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）中的白质损伤是否由髓磷脂或轴突损伤引起，以及这些变化是处于急性还是慢性阶段。 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、情绪和认知缺陷，可能是由于间歇性缺氧和伴随病情的灌注变化引起的神经过程受损所致。确定髓磷脂损伤与轴突损伤的需要取决于神经保护干预措施，以防止进一步损伤；针对髓磷脂与轴突保护存在特定的治疗方案。我们还需要知道这些纤维变化是最近发生的，还是已经存在很长时间了，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洞察力。 OSA 中灰质和白质组织均受到影响；然而，连接灰质结构的白质变化的性质尚不清楚。我们将评估整个大脑白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磷脂或轴突的变化。我们还将评估选定纤维束的纤维特性，根据其他证据，已知这些纤维束有助于心血管、记忆并影响 OSA 中突出的缺陷。研究将使用最近诊断的、未接受过治疗的中度至重度 OSA 受试者以及年龄和性别匹配的对照受试者。通过基于扩散张量成像（DTI）和扩散峰度成像（DKI）的平均扩散率和平均峰度指数来检查白质损伤的病理阶段。髓磷脂与轴突的变化将通过基于 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来评估，这些测量分别显示轴突和髓磷脂的变化。我们将同时使用 DTI 和 DKI 技术，因为每种程序都有独特的优势。更详细的髓磷脂评估将通过磁化转移成像（MTI）程序进行。最后，将通过纤维束描记术评估纤维数量、平均长度和其他纤维特性。我们的初步数据表明，OSA的脑白质损伤主要处于早期阶段，并且主要由髓磷脂的变化引起，尽管新诊断患者的特定部位也出现轴突变化。 OSA 的心血管和神经心理后遗症很严重，并且在肥胖、老年男性和绝经后女性中尤为突出。防止病理基础上的神经变化将极大地促进国家医疗保健。这些研究有可能确定 OSA 的白质病理变化，从而指出最适合该综合征的神经保护和恢复的干预措施。]