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

职业：新生儿臂丛神经麻痹损伤机制及预防策略研究

• 批准号: 2335643
• 负责人: Anita Singh
• 金额: $ 54.92万
• 依托单位: Temple University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2335643&HistoricalAwards=false
• 关键词: CAREER; Investigating; Injury; Mechanism; Prevention

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.

臂丛神经是从颈部的脊髓到手臂的一组神经。在分娩期间，这组神经可能会受到机械力，例如拉伸和拉动。臂丛神经的这种拉伸损伤称为新生儿臂丛神经麻痹，可能导致瘫痪程度不同。尽管新生儿臂丛神经麻痹可能对迁移率有害，但很少有数据描述了伸展的新生儿组织如何促进损伤或如何预防损伤，尤其是在与氧气饥饿的情况下与困难分娩有关的情况下。这项研究将定义损伤阈值，即，使用动物模型通过拉伸而无法延伸组织结构的点。组织特性数据将用于开发能够预测人类损伤阈值的计算模型，该模型可用于通过培训和教育来推动产科护理科学。该研究将检验与解剖位置，结构组成和组织上施加的力的大小有关的假设，以与组织失败和恢复速率的影响。研究和教育是通过基于本科和研究生实验室的研究整合的，开发了有关生物医学工程与临床需求相结合的新研究生课程，并在费城地区提供的动手活动中促进了服务不足的学校的生物医学工程。辛格博士的长期职业目标是通过提供对伤害机制的详细理解，并根据基本知识制定预防和治疗策略，从而最大程度地减少新生儿臂丛神经麻痹的发生。为了实现这一目标，辛格博士的研究目标是：（1）对新生儿小猪中正常和缺氧的新生儿臂神经丛的生物力学，生理和组织学特性提供了详细的理解； （2）利用动物模型数据训练计算模型来研究出生过程对臂丛神经的影响。将要测试的特定假设包括：（1）新生儿臂丛神经组织将在根/躯干段失败； （2）组织应变率对应于损伤恢复率； （3）拉伸的程度直接影响组织学结果。体内生物力学测试将使用大动物替代物进行。实验将使用高速相机，神经生理记录和组织学评估来评估拉伸和应变的影响。从现有框架开始的计算模型开发将集中于合并新生儿臂神经丛机械性能的参数。从这些研究中获得的见解将弥合当前的知识差距，将新生儿臂神经丛的功能响应与损伤阈值连接起来，以实现永久损害。这项研究将以有希望的临床翻译工具为最终，旨在降低出生时人类伤害的患病率。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子和更广泛影响的评估评估来支持的。