Postnatal Intermittent Hypoxia and Respiration: Potenti*

产后间歇性缺氧和呼吸：电位*

• 批准号: 7248678
• 负责人: STEPHEN R REEVES
• 金额: $ 3.32万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7248678
• 关键词: Clinical Medicine; Condition; Development; Environmental air flow; Hypoxia; Mammals; Mediating; Modification; Morbidity - disease rate; Motor; Nerve; Neuronal Plasticity; Neurons; Pathway interactions; Pattern; Phase; Protein Kinase C; Rattus; Respiration; Role; Signal Pathway; Sleep Apnea Syndromes; Stimulus; Structure of phrenic nerve; Sudden infant death syndrome; System; Ursidae Family; Work; awake; conditioning; insight; mortality; post-natal intermittent hypoxia; postnatal; respiratory; response

DESCRIPTION (provided by applicant): Intermittent hypoxia (IH) is a frequent condition in clinical medicine (e.g., sleep apnea, SIDS), which bears substantial morbidity and mortality. Furthermore, organismal adaptations to IH suggest the formation of specific forms of neuronal plasticity. While substantial study of the effects of IH has been performed in the mature mammal, little if any work has been done during the early phases of post-natal development, a unique period of neuronal vulnerability and adaptation. Therefore, we hypothesized that post-natal intermittent hypoxia, such as occurs in sleep apnea, may impose long-term modifications in respiratory control, thereby leading to a form of metaplasticity of respiratory patterning. The latter modification of the respiratory network induced by early post-natal IH could impose either a functionally favorable or a maladaptive alteration of the respiratory response system. To examine this issue, we will: (i) characterize the effects of post-natal IH on normoxic ventilation and on hypoxic and hypercapnic ventilatory responses in freely behaving rats.; (ii) assess the effects of IH on phrenic motor nerve long-term facilitation (LTF).; (iii) determine the potential role of signaling pathways, particularly protein kinase C (PKC), in the long-term modification of ventilation imposed by IH through development. This work will therefore contribute to the understanding of potential mechanisms mediating not only early adaptations to IH but also provide insights to long-lasting changes in ventilation that may develop when a conditioning stimulus is applied during critical phase of maturation.

描述（由申请人提供）：间歇性缺氧（IH）是临床医学中的常见病症（例如睡眠呼吸暂停、SIDS），具有很高的发病率和死亡率。此外，机体对 IH 的适应表明特定形式的神经元可塑性的形成。虽然对成熟哺乳动物的 IH 影响进行了大量研究，但在产后发育的早期阶段（神经元脆弱性和适应的独特时期）几乎没有做任何工作。因此，我们假设产后间歇性缺氧，例如睡眠呼吸暂停中发生的缺氧，可能会对呼吸控制造成长期改变，从而导致呼吸模式的某种形式的化生。产后早期 IH 引起的呼吸网络的后一种改变可能会对呼吸反应系统造成功能有利或适应不良的改变。为了研究这个问题，我们将：（i）描述产后 IH 对自由行为大鼠的常氧通气以及低氧和高碳酸血症通气反应的影响。 (ii) 评估 IH 对膈运动神经长期促进 (LTF) 的影响。 (iii) 确定信号通路，特别是蛋白激酶 C (PKC) 在 IH 发育过程中对通气的长期改变中的潜在作用。因此，这项工作将有助于理解潜在机制，不仅介导 IH 的早期适应，而且还提供对通气长期变化的见解，这种变化可能在成熟的关键阶段施加调节刺激时发生。