Consequences of Neonatal Hypoxia

新生儿缺氧的后果

• 批准号: 6990544
• 负责人: Nanduri R Prabhakar
• 金额: $ 37.35万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-12-15 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6990544
• 关键词: acetylcholine; age difference; apnea; carotid body; cell morphology; dopamine; free radical oxygen; free radical scavengers; hypercapnia; hypoxia; laboratory rat; mature animal; neurotransmitter transport; newborn animals; nitric oxide; pulmonary respiration; substance P; voltage /patch clamp

DESCRIPTION (provided by applicant): It is being increasingly recognized that 50% of prematurely born infants suffer with recurrent apneas that can be often fatal. Apneas are associated with intermittent hypoxemia. Hypoxia is sensed by the carotid bodies and the ensuing reflexes are critical for maintaining homeostasis. However, in neonates, carotid bodies and chemoreflex pathway are immature. The overall goal of the proposed research is to understand the consequences of neonatal hypoxemia on carotid bodies and ventilatory response to hypoxia. Based on our preliminary data, we hypothesize that: a) neonatal intermittent hypoxia promotes the developmental maturity of carotid bodies, which in turn improves ventilatory response to hypoxia, and b) IH-induced maturational changes in the carotid body involve increased generation of reactive oxygen species (ROS) leading to alterations in excitability and/or [Ca2+]i homeostasis and/or transmitter mechanisms in the glomus cells. We propose to test these hypotheses on neonatal rat pups because they resemble immature infants in terms of neuronal maturity. An integrated approach will be employed using a repertoire of techniques ranging from ventilatory measurements in intact animals to sensory activity measurements from carotid body to ion channel and transmitter measurements in isolated glomus cells. Experiments proposed in Aim 1 define the factors that contribute to IH-induced maturity of the carotid body sensitivity to hypoxia. Protocols in Aim 2 determine ventilatory patterns in IH-conditioned rat pups and assess the potential contribution of carotid bodies. Experiments in Aim 3 are aimed at assessing the cellular mechanism(s) underlying IH-induced developmental maturation of carotid body function and determine potential role of ROS. Understanding the consequences of neonatal IH provide insights into how neonatal intermittent hypoxia caused by recurrent apneas affects the ventilation in premature infants. Experimental Animal Model: Rat Pups.

描述（由申请人提供）：越来越多的人认识到，50%的早产婴儿患有复发性呼吸暂停，这通常是致命的。呼吸暂停与间歇性低氧血症有关。颈动脉体感知到缺氧，随后的反射对维持体内平衡至关重要。然而，在新生儿中，颈动脉体和化学反射通路尚不成熟。拟议研究的总体目标是了解新生儿低氧血症对颈动脉体的影响和对缺氧的通气反应。根据我们的初步数据，我们假设：a)新生儿间歇性缺氧促进颈动脉体发育成熟，从而改善对缺氧的通气反应；b) ih诱导的颈动脉体成熟变化涉及活性氧（ROS）的产生增加，导致血管球细胞兴奋性和/或[Ca2+]i稳态和/或递质机制的改变。我们建议在新生大鼠幼崽身上测试这些假设，因为它们在神经元成熟度方面类似于未成熟的婴儿。综合方法将采用一系列技术，从完整动物的通气测量到颈动脉体的感觉活动测量，再到分离血管球细胞的离子通道和递质测量。Aim 1中提出的实验定义了影响ih诱导颈动脉体缺氧敏感性成熟的因素。Aim 2中的方案确定了ih条件大鼠幼崽的通气模式，并评估了颈动脉体的潜在贡献。Aim 3的实验旨在评估ih诱导颈动脉体功能发育成熟的细胞机制，并确定ROS的潜在作用。了解新生儿IH的后果有助于了解复发性呼吸暂停引起的新生儿间歇性缺氧如何影响早产儿的通气。实验动物模型：大鼠幼仔。