CAREER: Investigating Injury Mechanism and Prevention Strategies of Neonatal Brachial Plexus Palsy

臂丛是一组从颈部的脊髓向下延伸到手臂的神经。在分娩过程中，这组神经可能会被机械力损伤，比如拉伸和拉扯。这种臂丛牵拉损伤称为新生儿臂丛麻痹，可导致不同程度的瘫痪。尽管新生儿臂丛麻痹可能会对活动能力造成相当不利的影响，但几乎没有数据描述拉伸的新生儿组织如何导致损伤或如何预防损伤，特别是在与难产相关的缺氧条件下。这项研究将使用动物模型来定义损伤阈值，即组织结构通过拉伸而不可修复地改变的点。组织特性数据将用于开发能够预测类似人类的损伤阈值的计算模型，该模型可用于通过培训和教育促进产科护理的科学。这项研究将测试与解剖位置、结构组成和施加在组织上的力的大小对组织衰竭和恢复率的影响有关的假说。通过本科生和研究生实验室研究，开发生物医学工程与临床需求相结合的新研究生水平课程，以及通过动手活动在费城地区服务不足的学校促进生物医学工程，将研究和教育结合在一起。辛格博士的长期职业目标是通过提供对损伤机制的详细了解，最大限度地减少新生儿臂丛麻痹的发生，并基于基础知识制定预防和治疗策略。为了实现这一目标，Singh博士的研究目标是：(1)详细了解新生仔猪正常和缺氧新生儿臂丛的生物力学、生理学和组织学特性；(2)利用动物模型数据训练计算模型，以研究分娩过程对臂丛的影响。将被测试的具体假设包括：(1)新生儿臂丛组织将在根部/躯干节段失效；(2)组织应变率与损伤恢复率相对应；(3)拉伸程度直接影响组织学结果。体内生物力学测试将使用大型动物代用品进行。实验将使用高速摄像机、神经生理学记录和组织学评估来评估拉伸和拉伸的影响。计算模型的开发，从现有的框架开始，将重点放在纳入新生儿臂丛机械特性的参数上。从这些研究中获得的见解将弥合目前的知识鸿沟，将新生儿臂丛的功能反应与永久性损伤的损伤阈值联系起来。这项研究最终将推出一种有前景的临床翻译工具，旨在减少出生时人类伤害的发生率。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The brachial plexus is a group of nerves traveling from the spinal cord in the neck down to the arm. During childbirth, this group of nerves can be injured by mechanical forces, like stretching and pulling. Such a stretch injury to the brachial plexus is called neonatal brachial plexus palsy and can result in varying degrees of paralysis. Though neonatal brachial plexus palsy can be quite detrimental to mobility, there is little data describing how stretching neonatal tissue contributes to injury or how to prevent it, particularly while under the oxygen-starved conditions associated with difficult births. This study will define injury thresholds, i.e., the point at which the tissue structure is irreparably changed by stretching, using animal models. The tissue property data will be used to develop a computational model capable of predicting human-like injury thresholds, which can be used to advance the science of obstetrical care through training and education. The study will test hypotheses relating anatomical location, structural composition, and magnitude of forces exerted on the tissue to the effects on tissue failure and rate of recovery. Research and education are integrated through undergraduate and graduate laboratory-based research, development of a new graduate-level course on integration of biomedical engineering with clinical need, and promoting biomedical engineering in underserved schools of the Philadelphia region with hands-on activities. Dr. Singh's long-term career goal is to minimize the occurrence of neonatal brachial plexus palsy by providing a detailed understanding of the injury mechanism and to develop prevention and treatment strategies based on fundamental knowledge. Toward this goal, Dr. Singh's research objectives are to: (1) provide a detailed understanding of the biomechanical, physiological, and histological properties of both the normal and hypoxic neonatal brachial plexus in neonatal piglets; and (2) utilize the animal model data to train a computational model to investigate the effects of the birth process on the brachial plexus. Specific hypotheses that will be tested include: (1) neonatal brachial plexus tissue will fail at the root/trunk segment; (2) tissue strain rate corresponds to rate of injury recovery; and (3) the extent of stretch directly affects histological outcome. In vivo biomechanical testing will be conducted using large animal surrogates. Experiments will evaluate the effects of stretch and strain using high-speed cameras, neurophysiological recordings, and histological assessments. The computational model development, starting from an existing framework, will focus on incorporating the parameters for neonatal brachial plexus mechanical properties. The insights gained from these studies will bridge a current knowledge gap, connecting the functional response of the neonatal brachial plexus with injury threshold for permanent damage. The research will culminate with a promising clinical translational tool aimed at reducing the prevalence of human injury at birth.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.