Time-Dependent Changes in Respiratory Control After Perinatal Hyperoxia

围产期高氧后呼吸控制的时间依赖性变化

基本信息

批准号：
7456087
负责人：
RYAN W BAVIS
金额：
$ 21万
依托单位：
BATES COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-01 至 2011-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7456087
关键词：
Acute Adult Adverse effects Afferent Neurons Age Age-Years Antioxidants Apnea Attenuated Birth Breathing Carotid Body Cause of Death Chemoreceptors Chemosensitization Condition Data Denervation Development Environmental air flow Equilibrium Exposure to Hand Hyperoxia Hypersensitivity Hypoxia Impairment In Vitro Individual Infant Life Life Experience Lung diseases Measurement Measures Modeling Neonatal Neonatal Intensive Care Units Nerve Nervous system structure Neural Pathways Neurons Nitric Oxide Synthase Type I Nucleus solitarius Oxygen Perinatal Peripheral Property Public Health Range Rattus Residual state Respiration Disorders Risk Structure Sudden infant death syndrome System Techniques Testing Time Week attenuation carotid sinus critical developmental period day experience inhibitor/antagonist neonate neuromechanism neurophysiology novel postnatal research study respiratory response

项目摘要

DESCRIPTION (provided by applicant): Experiences during early life can have profound effects on the developing nervous system, including neural pathways responsible for the control of breathing. This project will use hyperoxia as a model to study environmental effects on the control of breathing as well as the body's response to perturbations in this critical homeostatic system. The hypoxic ventilatory response is attenuated in adult rats exposed to perinatal hyperoxia due to abnormal development of the carotid body and its afferent neurons, but little is known about respiratory control in these rats during the neonatal period. Although carotid body function is greatly diminished immediately after exposure to hyperoxia, preliminary data suggest that the respiratory control system compensates for this impairment, at least transiently, since hypoxic ventilatory responses appear normal in young rats. Indeed, it appears that hyperoxia elicits multiple forms of respiratory plasticity during development, some that are excitatory and some that are inhibitory, and that the balance among these influences changes over time. Ventilation measurements and neurophysiological techniques will be used to extend these novel observations over a range of postnatal ages and to explore the underlying mechanisms for time-dependent changes in respiratory control. The three specific aims of this project are: (1) to test the hypothesis that perinatal hyperoxia causes time-dependent changes in ventilation in rats, including an initial potentiation of the hypoxic ventilatory response followed by a persistent attenuation, (2) to test the hypothesis that these time- dependent changes in the hypoxic ventilatory response correlate to changes in carotid body function, and (3) to test the hypothesis that other components of the respiratory control system are upregulated after perinatal hyperoxia, thereby compensating for impaired carotid body development. If excitatory plasticity compensates for attenuated carotid body function in neonates, these mechanisms may ameliorate the adverse effects of impaired ventilatory chemoreflexes during critical periods of development. On the other hand, if hyperoxia potentiates chemoreceptor and ventilatory responses to hypoxia, this hypersensitivity could increase the risk of apneas and breathing instabilities. PUBLIC HEALTH RELEVANCE: The proposed experiments have particular relevance to infants that receive supplemental oxygen in neonatal intensive care units. Abnormal development of chemoreceptors and protective chemoreflexes may increase the risk of respiratory disorders and sudden infant death syndrome, a major cause of death in infants 1 month to 1 year of age. Therefore, it is critical to understand how environmental conditions in early life influence development of protective chemoreflexes.

描述（由申请人提供）：早年的经历会对发育中的神经系统产生深远的影响，包括负责控制呼吸的神经通路。该项目将使用高氧作为模型来研究环境对呼吸控制的影响以及身体对这一关键稳态系统扰动的反应。由于颈动脉体及其传入神经元发育异常，暴露于围产期高氧的成年大鼠的缺氧通气反应减弱，但对这些大鼠在新生儿期的呼吸控制知之甚少。尽管颈动脉体功能在暴露于高氧后立即大大减弱，但初步数据表明，呼吸控制系统至少暂时补偿了这种损伤，因为低氧通气反应在幼年大鼠中表现正常。事实上，高氧似乎在发育过程中引发了多种形式的呼吸可塑性，一些是兴奋性的，一些是抑制性的，并且这些影响之间的平衡随着时间的推移而变化。通气测量和神经生理学技术将用于将这些新观察结果扩展到一系列出生后年龄，并探索呼吸控制随时间变化的潜在机制。该项目的三个具体目标是：(1) 检验围产期高氧导致大鼠通气随时间变化的假设，包括缺氧通气反应的初始增强，随后持续减弱，(2) 检验假设缺氧通气反应的这些时间依赖性变化与颈动脉体功能的变化相关，并且（3）检验围产期高氧后呼吸控制系统的其他组成部分上调的假设，从而补偿受损的颈动脉体发育。如果兴奋性可塑性补偿了新生儿颈动脉体功能的减弱，这些机制可能会改善发育关键时期通气化学反射受损的不利影响。另一方面，如果高氧会增强化学感受器和通气对缺氧的反应，这种超敏反应可能会增加呼吸暂停和呼吸不稳定的风险。公共健康相关性：拟议的实验与在新生儿重症监护病房接受补充氧气的婴儿特别相关。化学感受器和保护性化学反射的异常发育可能会增加呼吸系统疾病和婴儿猝死综合症的风险，这是 1 个月至 1 岁婴儿死亡的主要原因。因此，了解生命早期的环境条件如何影响保护性化学反射的发展至关重要。