Brain Changes in Pediatric Obstructive Sleep Apnea

小儿阻塞性睡眠呼吸暂停的大脑变化

• 批准号: 10468277
• 负责人: Rajesh Kumar
• 金额: $ 19.5万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-11 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468277
• 关键词: Acute; Adenoidal structure; Adenoidectomy; Affect; Aftercare; Anti-Inflammatory Agents; Area; Arousal; Axon; Behavior; Behavioral; Brain; Brain Injuries; Breathing; Cerebellum; Cerebrovascular Circulation; Characteristics; Child; Child Behavior Checklist; Childhood; Chronic; Clinical Trials; Cognition; Cognitive; Contrast Media; Development; Diffuse; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Early Intervention; Emotions; Endothelial Cells; Evaluation; External Capsule; FDA approved; Fiber; Functional Magnetic Resonance Imaging; Functional disorder; Health; Hippocampus (Brain); Hypercapnia; Hypoxia; Image; Imaging Techniques; Impaired cognition; Injury; Insula of Reil; Internal Capsule; Intervention; Magnetic Resonance Imaging; Measures; Methods; Moods; Morbidity - disease rate; Myelin; Nature; Non-Steroidal Anti-Inflammatory Agents; Obstructive Sleep Apnea; Operative Surgical Procedures; Outcome; Pathologic; Patients; Performance; Perfusion; Pharmaceutical Preparations; Positron; Procedures; Process; Radial; Radiation; Recovery; Reproducibility; Risk; Schools; Site; Sleep; Sleep Fragmentations; Source; Stroke; Symptoms; Syndrome; Thalamic structure; Tissues; Tonsil; Tonsillectomy; Traumatic Brain Injury; affective disturbance; airway obstruction; arterial spin labeling; axon injury; base; blood oxygen level dependent; brain tissue; cognitive benefits; cognitive control; cognitive function; effective therapy; improved; neural repair; neuroprotection; relating to nervous system; response; stem; tissue injury; water diffusion

PROJECT SUMMARY/ ABSTRACT Pediatric obstructive sleep apnea (OSA) is a common and progressive syndrome accompanied by severe cognition, mood, and daytime behavioral issues, as well as poor school performance, presumably stemming from compromised neural tissue, induced by intermittent hypoxia and perfusion changes. However, it is unclear whether the brain tissue injury is in acute or chronic condition, and whether myelin is preferentially affected than axons, an essential step to understand, since interventions for neural repair/recovery differ for acute vs chronic and myelin vs axonal injury. Also, it is unclear whether accompanying brain changes in pediatric OSA have functional consequences, resulting to cognitive or mood deficits. In addition, intermittent hypoxia triggers a cascade of injurious processes affecting endothelial cells, but unclear whether regional cerebral blood flow (CBF) is reduced in pediatric OSA. Treatment methods for pediatric OSA include tonsillectomy and/or adenoidectomy, and it is unclear whether brain tissue changes, regional CBF, and neural responses to cognitive challenge improve post-treatment. Using diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI)-based procedures, acute and chronic tissue changes and axonal status and myelin integrity can be assessed. Regional brain CBF can be assessed by validated arterial spin labeling (ASL) imaging, and regional neural activity to cognitive challenge can be examined with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (MRI). Thus, using 28 treatment-naïve, pediatric OSA and 28 control children, the specific aims are to; determine the nature and types of brain tissue injury, using DTI and DKI measures, in untreated pediatric OSA over healthy controls; identify regional brain CBF, using ASL imaging, and neural responses to cognitive challenge, using BOLD functional MRI in pediatric OSA over healthy children; assess cognitive (by the differential ability scale II and NEPSY II) and emotion functions (by the child behavior checklist) in pediatric OSA compared to control children, and examine relationships between brain injury and cognitive and emotion dysfunctions in pediatric OSA; and examine whether brain tissue changes, reduced CBF, and altered neural responses to cognitive challenge reverse, and cognition and mood signs improve after adenotonsillectomy at 6 months in pediatric OSA. In summary, the nature and types of brain injury, regional CBF changes, and neural responses to cognitive challenge, and whether brain tissue changes, altered CBF, and diminished neural responses, as well as mood and cognitive functions recover after adenotonsillectomy in pediatric OSA will be examined. Evaluation of pathological characteristics is essential to assess the mechanisms of damage, and to suggest intervention strategies before and after surgery. The findings will also help guide potential treatments to rescue/restore brain tissue (e.g., nonsteroidal anti-inflammatory drugs) and improve CBF that could be implemented to benefit cognitive and mood health, and improve academic performance in pediatric OSA.

项目摘要/摘要 小儿阻塞性睡眠呼吸暂停（OSA）是一种常见的进行性综合征 认知，情绪和白天的行为问题以及学校表现不佳，大概是促使 由间歇性缺氧和灌注变化引起的神经组织受损。但是，还不清楚 脑组织损伤是否处于急性或慢性病，以及髓磷脂是否比 轴突是理解的重要步骤，因为神经修复/恢复的干预措施与急性与慢性 和髓磷脂与轴突损伤。另外，还不清楚小儿OSA参与大脑的变化是否 功能后果，导致认知或情绪定义。此外，间歇性缺氧会触发A 影响内皮细胞的一系列有害过程，但尚不清楚区域脑血流（CBF）是否 小儿OSA减少。小儿OSA的治疗方法包括扁桃体切除术和/或腺样体切除术， 目前尚不清楚脑组织是否改变，区域CBF和对认知挑战的神经反应 改善后处理。使用扩散张量成像（DTI）和基于扩散的峰度成像（DKI） 可以评估程序，急性和慢性组织变化以及轴突状态以及髓磷脂完整性。区域 可以通过经过验证的动脉自旋标记（ASL）成像和区域神经活动来评估脑CBF 可以使用血氧级依赖性（粗体）功能磁共振检查认知挑战 成像（MRI）。使用28个治疗方法，儿科OSA和28名对照儿童，具体的目的是； 在未处理的小儿OSA中，使用DTI和DKI测量确定脑组织损伤的性质和类型 过度健康控制；使用ASL成像识别区域脑CBF以及对认知的神经反应 挑战，在儿科OSA中使用大胆​​的功能性MRI对健康的儿童；评估认知（通过差异 能力量表II和NEPSY II）和情感功能（通过儿童行为清单）在儿科OSA中 控制儿童，以及脑损伤与认知和情感功能障碍之间的关系 小儿OSA；并检查脑组织是否改变，CBF减少以及对神经反应的改变 认知挑战逆转，在6个月（6个月） 小儿OSA。总而言之，脑损伤的性质和类型，区域CBF变化和神经反应 认知挑战以及脑组织是否改变，CBF改变并减少神经反应，因为 如小儿OSA的腺骨切除术后的情绪和认知功能恢复一样。 评估病理特征对于评估损害机制至关重要，并建议 手术前后的干预策略。这些发现还将帮助指导潜在的治疗 营救/恢复脑组织（例如非甾体类抗炎药），并改善CBF 实施以使认知和情绪健康受益，并提高儿科OSA的学习成绩。