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）中的白质损伤是由髓磷脂或轴突损伤导致的，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，伴随着严重的心血管，代谢，记忆，情绪和认知缺陷，可能是由于伴随这种情况伴随的间歇性缺氧和灌注变化引起的神经过程所造成的。确定髓磷脂与轴突损伤的需求是对神经保护的干预措施，以防止进一步损伤。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的变化是最近的，还是长期存在的，这是通过通风仅通过通风的支持程序而不是神经保护干预措施进行的潜在恢复所必需的见解。 OSA中灰质和白质组织都受到影响；但是，白质变化的性质互连灰质结构尚不清楚。我们将评估整个大脑中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出髓磷脂或轴突的变化。我们还将评估所选纤维束的纤维特性，从其他证据来看，这些纤维束有助于心血管，记忆和影响OSA中明显的缺陷。研究将使用最近诊断的，幼稚的，中度至重度OSA受试者以及年龄和性别匹配的对照受试者。将通过扩散张量成像（DTI）和扩散峰度成像（DKI）基于基于基于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的轴向扩散性和轴向峰度以及径向扩散性和径向峰度测量方法来评估，分别显示轴突和髓磷脂变化。我们将同时使用DTI和DKI技术，因为每个过程都具有独特的优势。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，将通过纤维拖拉机评估纤维，平均长度和其他纤维特性的数量。我们的初步数据表明，OSA的白质损伤主要是在早期，并且主要是由于髓磷脂的变化而引起的，尽管轴突变化也出现在新诊断的患者的特定部位中。 OSA的心血管和神经心理学后遗症很严重，在病情，肥胖，老年男性和绝经后妇女的靶标中很突出。保护病理学基础的神经变化将极大地促进国家卫生保健。这些研究有可能确定OSA中的白质病理变化，因此指出了最适合综合征神经保护和恢复的干预措施。]