NEURAL MECHANISMS OF APNEA

新生儿的正常呼吸控制，就像成年人一样，取决于 组成脑干的神经元网络之间的相互作用 呼吸中心。然而，新生儿特别容易患上 不稳定的呼吸模式，表明这些 在出生后时期的相互作用。这样做的长期目标是 实验室将表征兴奋性和抑制性中枢神经元 控制自主神经功能的机制，包括 呼吸驱动，在新生儿期。该计划的主要目标是 目前的研究是表征神经细胞的发育。 负责整合外周化学感觉输入的通路。我们 将确定神经递质基因表达的调控机制 以及这些神经元在发育过程中的电生理反应。 此外，这些研究将确定这一系统的发展情况 受出生前和出生后低氧血症影响。正则递进通过 明确的发育阶段对儿童的正常发育至关重要 呼吸控制系统。正常发育受阻 围产期因异常情况(如缺氧)而形成的模式 经期可导致系统功能障碍，可能导致生命 包括早产儿、婴儿呼吸暂停在内的威胁病理 呼吸暂停常见于大龄婴儿，以及婴儿猝死综合症。 免疫组织化学和原位杂交的初步研究 实验利用Fos蛋白表达作为第二和第二和 组成中枢性化学反射通路的高级神经元。FOS 蛋白质的表达是对传入突触传递的反应 从外周化学感觉结构发出的信号。此前， 我们使用这种方法来识别包括 成年大鼠中枢神经化学反射通路。目前的研究是 将在发育中的大鼠身上执行，包括：1)识别 构成化学反射通路的脑干神经元群 在出生后的发育过程中，2)确定前和后的影响 出生后低氧血症对这一途径发展的影响，以及3)确定 围产期低氧血症对神经递质相关基因表达的影响 在整个出生后早期发育过程中。 第二个系列的实验是为了确定 大鼠脑内缺氧敏感神经元的电生理特性 脑干区域被确定为包含化学反射途径。在……里面 后一种实验采用膜片钳记录体外培养的神经细胞 脑干切片制备将用于确定细胞机制 与产前和产后反应性降低相关 低氧血症。

Normal respiratory control in newborns, as in adults, is dependent on interactions among networks of neurons comprising the brain stem respiratory centers. However, newborns are particularly prone to develop unstable respiratory patterns, suggesting important differences in these interactions during the postnatal period. The long-range goals of this laboratory is to characterize excitatory and inhibitory central neuronal mechanisms which control autonomic nervous function, including respiratory drive, during the newborn period. The major objective of the present study is characterize the cellular development of the neural pathway responsible for integrating peripheral chemosensory input. We will identify mechanisms regulating expression of neurotransmitter genes and electrophysiologic responses of these neurons during development. Further, these studies will determine how development of this system is affected by pre- and postnatal hypoxemia. Regular progression through defined developmental stages is crucial for normal development of the respiratory control system. Disruption of the normal developmental pattern due to an abnormal condition (eg hypoxia) during the perinatal period can lead to system dysfunction possibly resulting in life threatening pathologies including apnea in premature infants, infantile apnea common in older infants, and Sudden Infant Death Syndrome. The initial series of immunohistochemical and in situ hybridization experiments utilize Fos protein expression as a marker for second and higher order neurons comprising the central chemoreflex pathway. Fos protein is expressed in response to afferent synaptically transmitted signals arising from the peripheral chemosensory structures. Previously, we used this approach to identify higher order neurons comprising the central neural chemoreflex pathway in adult rat. The present studies are to be performed in developing rats and include: 1) Identifying the brainstem neuronal populations that comprise the chemoreflex pathway during postnatal development, 2) Determine the effect of pre- and postnatal hypoxemia on development of this pathway, and 3) identify the effect of perinatal hypoxemia on neurotransmitter-related gene expression throughout early postnatal development. A second series of experiments is designed to determine the electrophysiologic properties of hypoxia sensitive neurons in the brainstem regions identified as containing the chemoreflex pathway. In this latter experiments patch-clamp recording of neurons in an ex vivo brainstem slice preparation will be used to determine cellular mechanisms associated with decreased responsiveness following pre- and post natal hypoxemia.