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。

基本信息

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
项目类别：
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

项目摘要

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).

能力协调呼吸，哺乳和吞咽是出生时生存所必需的。婴儿产前接触阿片类药物的吞咽效率和吞咽呼吸协调，感觉 - 运动对咽刺激和食管运动反射的反应，这通常会导致持续进食困难。燕子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颖的方法这允许沿着中间区域的中间区域可视化和记录大量神经元内侧网状形成和歧义核（NA），同时保留巨核solitarius核。我们通过同时对神经元的光学记录，证明了可靠的中央刺激 Na的半合理和紧凑区域以及神经根记录。 Na神经元的激活燕子期间受到产前阿片类药物的影响。我们的方法还允许叠加光学记录在随后的免疫组织化学图像上，以鉴定区域细胞表型和至确认录制位置。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协作工作中演变的研究人员，将中央神经回路，光学/组织学技术和燕子的调节。拟议的研究旨在描述主动神经元的位置和类型在吞咽过程中，在整个呼吸周期刺激燕子的变化以及新生儿的影响阿片类药物戒断综合征。结合的最新技术将提供急需的机械深入了解吞咽和临床观察新生儿阿片类药物戒断综合征（现在）。