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

• 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
• 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' 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

 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.