Blood-Brain Barrier Deficit and Brain Injury in Obstructive Sleep Apnea

阻塞性睡眠呼吸暂停中的血脑屏障缺陷和脑损伤

基本信息

批准号：
8887911
负责人：
Rajesh Kumar
金额：
$ 51万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-01 至 2019-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8887911
关键词：
Acute Affective Affective Symptoms Age Alzheimer&apos s Disease Antibodies Anxiety Area Arteries Bacteria Beck depression inventory Blood - brain barrier anatomy Blood Pressure Blood capillaries Body mass index Brain Brain Injuries Breathing Cerebellum Chemicals Chronic Cognition Cognitive Cognitive deficits Continuous Positive Airway Pressure Contrast Media Cortical Dysplasia Data Diffusion Diffusion Magnetic Resonance Imaging Disease Emotional Epilepsy Equipment and supply inventories Experimental Autoimmune Encephalomyelitis Gender Hippocampus (Brain)Hypoxemia Image Analysis Imaging Techniques Impairment Infection Injury Insula of Reil Lead Link Magnetic Resonance Imaging Measures Meningitis Methods Microscopic Moods Morbidity - disease rate Multiple Sclerosis Neurobehavioral Manifestations Obstructive Sleep Apnea Outcome Patients Pharmaceutical Preparations Pilot Projects Procedures Process Publishing Quality of life Radiation Reporting Sample Size Sampling Site Sodium Chloride Spin Labels Stroke Study of magnetics Symptoms Syndrome Testing Time Tissues Traumatic Brain Injury Water acute stroke anxiety symptoms base brain tissue capillary cognitive change cognitive function cognitive testing diffusion weighted effective intervention effective therapy frontal lobe hypoperfusion improved mild cognitive impairment mortality nerve injury patient population public health relevance relating to nervous system repaired treatment response water diffusion

项目摘要

DESCRIPTION (provided by applicant): Obstructive sleep apnea (OSA) patients show brain damage in areas that regulate autonomic (insular sites), cognition (hippocampus and frontal cortex), and breathing (cerebellum) functions. Structural deficits in these regions in OSA are associated with symptoms that are linked to increased morbidity, mortality, and decreased quality of life. However, the underlying processes contributing to brain injury in these sites in OSA are unknown. [Altered blood-brain barrier (BBB) function in OSA] is a potential cause of brain damage, as functional alterations in the BBB are linked with neural injury in other disease conditions. However, no reports of BBB changes are published in OSA or associated with any relationship between BBB function and brain injury in this condition. Using non-invasive magnetic resonance imaging (MRI) procedures, our preliminary studies are the first to show BBB abnormalities (via diffusion-weighted pseudo-continuous arterial spin labeling [pCASL] procedures) in OSA and that these BBB changes are associated with brain damage (as assessed by diffusion tensor imaging based mean diffusivity [MD], an MRI measure of tissue integrity) in the insular, hippocampal, frontal, and cerebellar areas, [and affective and cognitive changes in OSA over controls]. However, [the sample size in this pilot study did not allow us to control for significant covariates, such as age, gender, body mass index (BMI), and blood pressure]. Therefore, the specific [aims are to:] 1) compare BBB status (calculated from diffusion-weighted pCASL) between untreated, moderate-to-severe OSA and age-, gender, [BMI-matched] controls; 2) compare brain damage (assessed by MD) in the [insula, hippocampus, frontal cortices, and cerebellum, and affective and cognitive functions] between OSA and age-, gender-, and [BMI-matched] controls; 3) examine the relationships between altered BBB function (assessed by diffusion- weighted pCASL data) and insular, hippocampal, frontal, and cerebellar structural integrity (as indicated by MD) in OSA subjects; [and 4) in an exploratory aim, examine BBB integrity in a subset of OSA at 3 and 9 months of continuous positive airway pressure treatment and compare to pre-treatment responses and controls]. In summary, OSA subjects show brain damage in sites that control autonomic, cognitive, and breathing functions. A potential reason of this brain injury in OSA may be changes in the BBB function, [which has not been reported previously in OSA]. Our initial studies have shown that BBB function is altered, and this alteration is associated with brain damage in autonomic, cognitive, and breathing control sites. Information from this study has the potential to uncover the processes contributing to brain damage in OSA. Thus, it has important implications on identification of effective treatments for OSA by repairing BBB function, as used in other [acute (e.g., stroke, traumatic brain injury, and multiple sclerosis) and chronic (e.g., Alzheimer's disease, chronic hypoperfusion, cortical dysplasia, and autoimmune encephalomyelitis) onset conditions], which could dramatically improve the morbidity, mortality, and quality of life in this patient population.

描述（由适用提供）：阻塞性睡眠呼吸呼吸暂停（OSA）患者在调节自主神经（岛状地点），认知（海马和额叶皮层）以及呼吸（小脑）功能的区域显示脑损伤。 OSA中这些地区的结构定义与症状有关，这些症状与发病率，死亡率和生活质量的增加有关。但是，在OSA中这些部位导致脑损伤的基本过程尚不清楚。 [OSA中的血脑屏障（BBB）功能改变]是脑损伤的潜在原因，因为在其他疾病情况下，BBB的功能改变与神经损伤有关。但是，在这种情况下，没有在OSA中发表任何BBB变化的报告，也没有与BBB功能与脑损伤之间的任何关系有关。 Using non-invasive magnetic resonance imaging (MRI) procedures, our preliminary studies are the first to show BBB abnormalities (via diffusion-weighted pseudo-continuous arterial spin labeling [pCASL] procedures) in OSA and that these BBB changes are associated with brain damage (as assessed by diffusion tensor imaging based mean difference [MD], an MRI measurement of tissue integrity)在岛上的海马，额叶和小脑区域，[情感和认知 OSA对控件的变化。但是，[该试验研究中的样本量不允许我们控制重要的协变量，例如年龄，性别，体重指数（BMI）和血压]。因此，特定的目的是：] 1）比较未处理，中度至重度OSA和年龄，性别，[BMI匹配]对照之间的BBB状态（根据扩散加权PCASL计算）； 2）在OSA和年龄，性别 - 和[BMI匹配的]控制之间比较[岛，海马，额叶皮层和小脑以及情感和认知功能]中的脑损伤（由MD评估）； 3）检查改变BBB功能的改变（通过扩散加权PCASL数据评估）与OSA受试者中的岛屿，海马，额叶和小脑结构完整性（如MD所示）之间的关系； [和4）在探索性目的中，在3和9个月的连续气道压力处理中检查了OSA子集中的BBB完整性，并将其与预处理响应和对照相比]。总而言之，OSA受试者在控制自主神经，认知和呼吸功能的部位显示脑损伤。 OSA中这种脑损伤的潜在原因可能是BBB功能的变化，[尚未在OSA中报道]。我们的最初研究表明，BBB功能发生了变化，并且这种改变与自主，认知和呼吸控制位点的脑损伤有关。这项研究的信息有可能发现导致OSA脑损伤的过程。这是对通过修复BBB功能的有效治疗方法具有重要意义的，如其他[急性（例如，中风，脑外伤，脑损伤和多发性硬化症）和慢性（例如，阿尔茨海默氏病，慢性疾病，慢性疾病，慢性疾病，皮质性增生性疾病和自身免疫性症状）的杂音，这是杂乱无章的杂音，这是杂乱无章的杂音，这是杂乱无章的。死亡率和生活质量患者人数。