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.

臂丛神经是一组从颈部脊髓到手臂的神经。在分娩过程中，这组神经可能会受到机械力的损伤，如拉伸和拉扯。这种臂丛神经的牵张性损伤称为新生儿臂丛神经麻痹，可导致不同程度的瘫痪。虽然新生儿臂丛神经麻痹可能对活动性非常有害，但很少有数据描述拉伸新生儿组织如何导致损伤或如何预防损伤，特别是在与困难分娩相关的缺氧条件下。本研究将定义损伤阈值，即，使用动物模型，组织结构因拉伸而不可挽回地改变的点。组织特性数据将用于开发能够预测类似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进产科护理科学。本研究将检验与解剖位置、结构组成和施加在组织上的力的大小对组织失效和恢复率的影响相关的假设。研究和教育是通过本科生和研究生实验室为基础的研究，开发一个新的研究生水平的生物医学工程与临床需要的整合课程，并促进生物医学工程在费城地区的服务不足的学校与实践活动相结合。Singh博士的长期职业目标是通过提供对损伤机制的详细了解来尽量减少新生儿臂丛神经麻痹的发生，并根据基本知识制定预防和治疗策略。为了实现这一目标，辛格博士的研究目标是：（1）提供对新生仔猪正常和缺氧新生臂丛神经的生物力学，生理学和组织学特性的详细了解;（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神经的影响。将检验的具体假设包括：（1）新生儿臂丛神经组织将在根/干段失效;（2）组织应变率对应于损伤恢复率;（3）拉伸程度直接影响组织学结局。将使用大型动物替代品进行体内生物力学试验。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应变的影响。计算模型的开发，从现有的框架，将集中在纳入新生儿臂丛神经的机械性能的参数。从这些研究中获得的见解将弥合当前的知识差距，将新生儿臂丛神经的功能反应与永久性损伤的损伤阈值联系起来。该研究将以一个有前途的临床转化工具达到高潮，该工具旨在减少人类出生时受伤的发生率。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。