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、吸吮和吞咽的能力是出生时生存所必需的。产前婴儿 接触阿片类药物可能会导致吞咽效率、吞咽呼吸协调、感觉异常 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 喂养困难。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方法 允许观察和记录沿着大脑中间区域的大量神经元 内侧网状结构和模糊核 (NA)，同时保留孤束核。我们 通过同时光学记录吞咽神经元来证明可靠的中枢刺激 NA 的半致密和致密区域，以及神经根记录。 NA 神经元的激活 吞咽期间受到产前阿片类药物暴露的影响。我们的方法还允许光学叠加 记录到随后的免疫组织化学图像上，以识别区域细胞表型并 确认录音地点。我们的工作假设是脑干吞咽网络跨越髓质 并且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公司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/组织学技术和 吞咽的调节。拟议的研究旨在描述活跃神经元的位置和类型 吞咽过程中，整个呼吸周期中吞咽受到刺激时的变化，以及新生儿的影响 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 新生儿阿片戒断综合征（NOWS）婴儿的吞咽和临床观察的深入研究。