POSTNATAL MATURATION OF CARDIOVASCULAR REGULATORY SYSTEM

产后心血管调节系统的成熟

• 批准号: 6625220
• 负责人: Anthony Louis Sica
• 金额: $ 30.99万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-08-01 至 2004-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6625220
• 关键词: age difference; brain mapping; cardiovascular function; denervation; developmental neurobiology; disease /disorder model; growth /development; hypercapnia; hypotension; infant animal; neural transmission; neuroregulation; phrenic nerve; respiration regulatory center; respiratory function; respiratory reflex; sudden infant death syndrome; swine; sympathetic nervous system

DESCRIPTION (Verbatim from the application): The overall goal of this proposal is to provide physiological and anatomical indices of maturation within neural networks involved in cardiorespiratory (CV-RESP) regulation. We shall focus on brainstem circuit neurons that mediate the CV-RESP responses to hypercapnic stress because: (a) this circuit plays an essential role in the maintenance of blood/gas homeostasis and (b) evidence suggesting that maladaptive responses to hypercapnic stimulation may be involved in the pathogenesis of Sudden Infant Death Syndrome (SIDS).The swine model of early development will be used to test the hypothesis that CV-RESP responses to prolonged hypercapnia are: (a) age-related, (b) modulated by peripheral afferent inputs, and (c) mediated by central a2-adrenoceptors. We also hypothesize that the network response to hypercapnia involves area postrema, nucleus tractus solitarii, and their synaptic targets within sympathetic (SYMP) control regions of the lateral medullary reticular formation. We shall test our hypothesis that catecholaminergic cell areas of the piglet medulla, previously shown to be activated by (a) CO2 and (b) hypotension, play crucial roles in the coordinated response. Of special significance are a subset of epinephrinergic neurons located in the SYMP premotor region of the rostral ventrolateral medulla. The effects of prolonged hypercapnia on SYMP outflow from at least two different segmental levels will be recorded, simultaneously with phrenic (PHR) activity. lEG expression will be quantitated with respect to age and brain stem sites. Age-related alterations in physiologic and neqronal responses to hypercapnia will be assessed following blockade of central alpha-2 receptors. Peripheral denervation will determine the importance of peripheral afferent inputs versus central effects ofhypercapnia at different ages. The correlation between lEG expression and SYMP-PHR outflows should reveal whether age-related changes in CV-RESP brain circuits (suggesting periods of vulnerability), are also observed in SYMP-PHR outflows; thus explaining the absence of a linear pattern of maturation of CV responses with stress. These studies should identify apparent dissociation between level of lEG expression (neuronal activation), SYMP coherence (regulatory outflow) and CV-RESP responses to stress (critical developmental period). The results should help in our understanding of the most vulnerable period in the life of the child and the pathogenesis ('window of opportunity') of SIDS.

描述（来自申请的逐字）：本提案的总体目标 是提供神经内成熟的生理和解剖学指标， 参与心肺调节的网络（CV-RESP）。我们要聚焦 介导CV-RESP对高碳酸血症反应的脑干回路神经元 压力，因为：（a）这个电路在维持 血液/气体稳态和（B）证据表明， 高碳酸血症刺激可能参与了猝死的发病机制 死亡综合征（SIDS）。将使用早期发育的猪模型来测试 假设CV-RESP对长期高碳酸血症的反应是：（a） 年龄相关，（B）由外周传入输入调节，和（c）由 中枢α 2肾上腺素受体。我们还假设，网络对 高碳酸血症涉及最后区，孤束核，以及它们的 交感神经（SYMP）控制区内的突触靶点 髓质网状结构。我们将检验我们的假设， 先前显示的仔猪髓质的儿茶酚胺能细胞区域 由（a）CO2和（B）低血压激活，在协调的 反应具有特殊意义的是肾上腺素能神经元的一个子集 位于延髓头端腹外侧区的SYMP运动前区。的 长期高碳酸血症对至少两种不同的SYMP流出的影响 将记录节段水平，同时记录膈神经（PHR）活动。 将根据年龄和脑干部位对IEG表达进行定量。 高碳酸血症引起的生理和呼吸反应的变化 将在阻断中枢α-2受体后进行评估。外围 去神经支配将决定外周传入输入与 不同年龄高碳酸血症的中枢效应。IEG之间的关系 表达和SYMP-PHR流出应揭示是否与年龄相关的变化， 还观察到CV-RESP脑回路（提示脆弱期） 在SYMP-PHR流出;从而解释了没有线性模式， CV反应与应激的成熟。这些研究应确定明显的 IEG表达水平（神经元活化）之间的分离，SYMP 一致性（调节流出）和CV-RESP对压力的反应（关键 发展时期）。这些结果应该有助于我们理解 儿童生命中的脆弱期和发病机制（“窗口期”） 机会”）。