Investigating Injury Tolerance and Mechanisms of Neonatal Brachial Plexus Palsy and Associated Injuries

新生儿臂丛神经麻痹（NBPP）是一种分娩并发症，可导致显著的长期 后遗症NBPP相关损伤通常包括脊髓损伤（SCI）的病例， 明白我们的长期研究目标是为NBPP制定预防和治疗策略。 因此，本研究的目的是使用我们的新型和独特的临床相关新生仔猪模型： a）通过以下方法确定导致形态和功能性SCI的臂丛神经（BP）张力和力： 研究BP拉伸对脊髓（SC）内急性病理学和功能的影响，B）为了 研究NBPP期间SCI早期诊断的临床相关全身生物标志物，以及c）开发 母亲骨盆和胎儿的计算模型，预测NBPP和相关SCI的风险， 复杂的NBPP交付场景。根据我们的初步工作，我们的中心假设是， 严重的BP拉伸会将力传递到SC，导致SC组织损伤，这也可以观察到， 血清和脑脊液中全身性损伤生物标志物的高表达， 运动神经元兴奋性我们的创新方法旨在开发急性NBPP损伤的新知识 机制，并报告BP应变和力的SCI耐受值。这些数据将使新的临床工具 用于诊断和预防，并为NBPP的早期临床干预提出目标。我们将测试 总体假设通过以下独立的具体目标：1）确定是否适度， 严重的BP拉伸将导致SCI，如急性SCI标记物原位所示，运动功能丧失， 神经元和全身性急性SCI生物标志物，以及2）识别分娩操作和NBPP风险 导致血压异常的因素，增加相关SCI的可能性。的 这项工作的预期成果是有史以来第一次的数据：1）形态和功能损伤的结果， 有助于确定BP拉伸期间BP应变和力的SCI耐受值，2）分子生物标记物， 可以实现SCI的早期诊断，以及3）开发用于NBPP预测的高度生物学计算模型 和产科培训。结果也将产生重要的积极影响，因为它们奠定了基础 开发一种新的有针对性的临床干预措施。

Neonatal Brachial Plexus Palsy (NBPP) is a complication of childbirth that can result in significant long-term sequelae. NBPP associated injuries often include cases of spinal cord injury (SCI) and are very poorly understood. Our long-term research goals are to develop both prevention and treatment strategies for NBPP. Consequently, objectives of this study are to use our novel and unique clinically-relevant neonatal piglet model: a) To identify brachial plexus (BP) strains and forces that lead to morphological and functional SCI by investigating the effects of BP stretch on acute pathology and functionality within the spinal cord (SC), b) To investigate clinically-relevant systemic biomarkers for early diagnosis of SCI during NBPP, and c) To develop computational models of maternal pelvis and fetus that predict risk of NBPP and associated SCI during complicated NBPP delivery scenarios. Based on our preliminary work, our central hypothesis is that moderate to severe BP stretches will transmit forces to SC resulting in SC tissue damage, which are also observable as high expression of systemic injury biomarkers in the serum and cerebrospinal fluid, and suppression or loss of motor neuron excitability. Our innovative approach is aimed at developing new knowledge of acute NBPP injury mechanisms and report SCI tolerance values of BP strains and forces. These data will enable novel clinical tools for diagnosis and prevention, as well as suggest targets for early clinical interventions for NBPP. We will test the overall hypothesis through the following independent specific aims: 1) To determine whether moderate to severe BP stretches will lead to SCI as evident by acute SCI markers in situ, functional loss in motor neurons and systemic acute SCI biomarkers, and 2) To identify delivery maneuvers and NBPP risk factors that lead to abnormal BP strains and forces, increasing the likelihood of associated SCI. The expected outcomes of this work are the first ever data on: 1) morphological and functional injury outcomes that help determine SCI tolerance values of BP strains and forces during BP stretch, 2) molecular biomarkers that can enable early diagnosis of SCI, and 3) developing highly biofidelic computational models for NBPP prediction and obstetric training. The results will also have an important positive impact, because, they lay the groundwork to develop a new class of targeted clinical interventions.