Delineating impacts of gestational opioid exposure on central swallow networks.

描述妊娠期阿片类药物暴露对中枢吞咽网络的影响。

• 批准号: 10573422
• 负责人: NICHOLAS M MELLEN
• 金额: $ 23.48万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10573422
• 关键词: Acute; Affect; Algorithms; Anatomy; Animals; Area; Birth; Brain Stem; Breathing; Breeding; Calcium; Cell Nucleus; Cells; Cervical; Child; Classification; Clinical; Color; Confocal Microscopy; Core Facility; Data; Data Collection; Deglutition; Deglutition Disorders; Development; Diagnosis; Dissection; Dorsal; Eating; Ensure; Esophagus motility; Exposure to; Female; Goals; Histologic; Histological Techniques; Human Milk; Hypoglossal nerve structure; Image; Immunohistochemistry; Infant; Injections; Label; Laboratories; Length of Stay; Location; Maps; Medial; Mediating; Methadone; Methods; Modeling; Motor; Motor Neurons; Motor output; Mus; Neonatal Abstinence Syndrome; Nerve; Neuromodulator; Neurons; Nucleus solitarius; Opioid; Optics; Patient Care; Pattern; Pharyngeal structure; Phenotype; Population; Preparation; Process; Reflex action; Regulation; Research Personnel; Reticular Formation; Rodent; Saline; Sensory; Somatostatin; Stimulus; Structure of phrenic nerve; Techniques; Technology; Testing; Tissues; Translations; Ventral Roots; Visualization; Withdrawal; Work; brain pathway; central pattern generator; cohort; design; experience; experimental study; feeding; fetal opioid exposure; hindbrain; histological image; indexing; insight; interest; machine vision; mouse model; neonate; neural circuit; neural patterning; new therapeutic target; novel; novel therapeutics; nucleus ambiguus; opioid exposure; opioid use in pregnancy; opioid withdrawal; postnatal period; prenatal exposure; preservation; public health relevance; pup; respiratory; response; screening; subcutaneous; suckling; tissue fixing

The ability coordinate breathing, suckling, and swallow is required for survival at birth. Infants with prenatal exposure to opioids can have abnormalities in swallow efficiency and swallow-breathing coordination, sensory- motor responses to pharyngeal stimulus, and esophageal motility reflexes, which often results in persistent feeding difficulties. The swallow pattern generator is located within the brainstem, but it has been difficult to study due to its location and widely dispersed neural circuits. Our preliminary studies describe a novel method that allows for the visualization and recording of a vast number of neurons along the intermediate zone of the medial reticular formation and Nucleus Ambiguus (NA), while preserving the Nucleus Tractus Solitarius. We demonstrate reliable central stimulation of swallow with simultaneous optical recording of neurons in the semicompact and compact regions of the NA, along with nerve root recordings. Activation of NA neurons during swallow is affected by prenatal opioid exposure. Our methods also allow superimposition of optical recordings onto subsequent immunohistochemical images to identify regional cellular phenotypes and to confirm recording locations. Our working hypothesis is that the brainstem swallow network spans the medulla and is vulnerable to opioids. The current application has evolved from collaborative work from two established investigators, bringing together expertise in central neural circuitry, optical/ histological techniques, and regulation of swallow. The proposed studies are designed to describe location and type of neurons active during swallow, alterations when swallow is stimulated across the respiratory cycle, and the impact of neonatal opioid withdrawal syndrome. The combined state-of-the-art techniques will provide much-needed mechanistic insight into swallow and clinical observation of infants with neonatal opioid withdrawal syndrome (NOWS).

协调呼吸、吮吸和吞咽的能力是出生时生存所必需的。产前有 暴露于阿片类药物可能会导致吞咽效率和吞咽呼吸协调，感觉， 对咽部刺激的运动反应和食管运动反射，这通常会导致持续的 进食困难。吞咽模式发生器位于脑干内，但很难 研究由于其位置和广泛分散的神经回路。我们的初步研究描述了一种新的方法 它允许沿着中间区沿着的大量神经元的可视化和记录。 内侧网状结构和疑核（NA），同时保留孤束核。我们 证明可靠的中枢刺激吞咽与同时光学记录的神经元在 NA的半致密和致密区域，沿着神经根记录。NA神经元的激活 在吞咽时受到产前阿片类药物暴露的影响。我们的方法还允许叠加光学 记录到随后的免疫组织化学图像上，以鉴定区域细胞表型， 确认录音地点我们的工作假设是脑干吞咽网络跨越延髓 容易受到阿片类药物的影响当前的应用程序是从两个已建立的应用程序的协作工作发展而来的 研究人员，汇集了中枢神经回路，光学/组织学技术， 调节吞咽。这些研究旨在描述活跃神经元的位置和类型 在吞咽过程中，当吞咽在呼吸周期中受到刺激时， 阿片类药物戒断综合征结合最先进的技术将提供急需的机械 新生儿阿片类戒断综合征（NOWS）患儿吞咽功能观察