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: 10218463
• 负责人: Rajesh Kumar
• 金额: $ 23.4万
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10218463
• 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; Spin Labels; Stroke; Symptoms; Syndrome; Thalamic structure; Tissues; Tonsil; Tonsillectomy; Traumatic Brain Injury; affective disturbance; airway obstruction; axon injury; base; blood oxygen level dependent; brain tissue; cognitive benefits; cognitive control; cognitive function; effective therapy; improved; neuroprotection; relating to nervous system; repaired; 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.

项目总结/摘要 儿童阻塞性睡眠呼吸暂停（OSA）是一种常见的进行性综合征， 认知、情绪和日间行为问题，以及学校表现不佳，可能是由于 由间歇性缺氧和灌注变化引起的受损神经组织。但目前尚不清楚 脑组织损伤是急性还是慢性，以及髓鞘是否优先受影响， 轴突，理解的一个重要步骤，因为神经修复/恢复的干预措施对于急性与慢性 和髓鞘与轴突损伤。此外，目前还不清楚儿童OSA伴随的大脑变化是否 功能性后果，导致认知或情绪缺陷。此外，间歇性缺氧会引发 影响内皮细胞的损伤过程级联，但不清楚局部脑血流量（CBF） 在儿童阻塞性睡眠呼吸暂停综合征中减少。小儿OSA的治疗方法包括扁桃体切除术和/或腺样体切除术， 目前还不清楚脑组织变化、局部CBF和对认知挑战的神经反应是否 改善后处理。使用基于扩散张量成像（DTI）和扩散峰度成像（DKI）的 可以评估手术、急性和慢性组织变化以及轴突状态和髓鞘完整性。区域 脑CBF可以通过有效的动脉自旋标记（ASL）成像和区域神经活动来评估， 认知挑战可以用血氧水平依赖性（BOLD）功能磁共振检查 成像（MRI）。因此，使用28名未经治疗的儿童OSA和28名对照儿童，具体目的是： 在未治疗的儿童OSA中，使用DTI和DKI测量确定脑组织损伤的性质和类型 与健康对照组相比;使用ASL成像和对认知的神经反应来识别区域脑CBF 挑战，使用BOLD功能性MRI在儿童OSA中超过健康儿童;评估认知（通过区分 能力量表II和NEPSY II）和情绪功能（通过儿童行为检查表）在儿童OSA中进行比较 控制儿童，并检查脑损伤与认知和情感功能障碍之间的关系， 儿童OSA;并检查脑组织是否发生变化，CBF是否减少，以及神经反应是否改变， 认知挑战逆转，认知和情绪体征改善后，6个月的腺样体切除术， 小儿OSA。总之，脑损伤的性质和类型、局部CBF变化和神经反应 认知挑战，以及脑组织是否发生变化、CBF改变和神经反应减弱， 以及儿童阻塞性睡眠呼吸暂停综合征患者行扁桃体切除术后情绪和认知功能的恢复情况。 病理学特征的评估对于评估损伤机制至关重要，并提示 手术前后的干预策略。这些发现还将有助于指导潜在的治疗方法， 挽救/恢复脑组织（例如，非甾体抗炎药），并改善CBF， 实施，以有利于认知和情绪健康，并提高儿童OSA的学业成绩。