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

研究新生儿臂丛神经麻痹及相关损伤的损伤耐受性和机制

• 批准号: 10366901
• 负责人: Sriram Balasubramanian
• 金额: $ 48.64万
• 依托单位: WIDENER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10366901
• 关键词: 3-Dimensional; Accounting; Acute; Animals; Area; Biochemical; Biological Assay; Biological Markers; Biomechanics; Brachial plexus structure; Cadaver; Cerebrospinal Fluid; Childbirth; Clinical; Complex; Complication; Computer Models; Data; Development; Devices; Diagnosis; Diagnostic; Discipline of obstetrics; Early Diagnosis; Early Intervention; Early treatment; Electrophysiology (science); Elements; Event; Failure; Fetus; Functional disorder; Gamma Motor Neurons; Goals; Head and neck structure; Hemorrhage; Histologic; Human; In Situ; Inflammatory Response; Injury; Intervention; Knowledge; Lateral; Lead; Maps; Modeling; Molecular; Morphology; Motor Neurons; Neonatal; Neurons; Outcome; Paralysed; Pathologic; Pathology; Pelvis; Prevention; Prevention strategy; Property; Proteomics; Publishing; Reporting; Research; Research Priority; Risk; Risk Factors; Science; Serum; Spinal; Spinal Cord; Spinal cord injury; Stretching; Testing; Therapeutic; Tissues; Training; United States National Institutes of Health; Visualization software; Work; avulsion injury; base; biochemical model; clinical development; clinical diagnostics; clinically relevant; combinatorial; diagnostic tool; disability; early detection biomarkers; fetal; force sensor; functional loss; functional status; in silico; in vivo; injury prevention; innovation; insight; long-term sequelae; molecular marker; motor neuron degeneration; neonatal care; neuroinflammation; next generation; novel; porcine model; predictive modeling; predictive tools; pressure; prevent; primipara; response; severe injury; simulation; tool; treatment strategy

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.

新生儿臂丛神经麻痹（NBPP）是分娩的并发症，可能会导致长期显着 后遗症。 NBPP相关的损伤通常包括脊髓损伤病例（SCI），并且非常差 理解。我们的长期研究目标是为NBPP制定预防和治疗策略。 因此，这项研究的目标是使用我们新颖且独特的临床新生小猪模型： a）鉴定臂丛神经（BP）菌株和力，从而导致形态学和功能性SCI 研究BP拉伸对脊髓内急性病理和功能的影响（SC），b） 调查与临床上相关的系统生物标志物，用于NBPP期间SCI的早期诊断，c）发展 预测NBPP和相关SCI风险的母体骨盆和胎儿的计算模型 复杂的NBPP交付方案。基于我们的初步工作，我们的中心假设是 到严重的bp伸展将传递力向SC传播，从而导致SC组织损伤，这也可以观察到 血清和脑脊液中系统性损伤生物标志物的高表达，抑制或丧失 运动神经元兴奋性。我们的创新方法旨在发展急性NBPP伤害的新知识 机理和报告BP菌株和力的SCI公差值。这些数据将实现新颖的临床工具 用于诊断和预防，并建议对NBPP早期临床干预的靶标。我们将测试 通过以下独立特定目的的总体假设：1）确定是否适度 严重的bp伸展将导致SCI被急性SCI标记，现场，电机功能损失 神经元和系统性急性科学生物标志物，以及2）确定递送操作和NBPP风险 导致BP菌株和力异常的因素，增加了相关SCI的可能性。这 这项工作的预期结果是有史以来的第一个数据：1）形态和功能损伤结果， 帮助确定BP拉伸期间BP菌株和力的SCI公差值，2）分子生物标志物 可以实现SCI的早期诊断，3）为NBPP预测开发高度生物质量计算模型 和产科培训。结果也将产生重要的积极影响，因为它们为基础奠定了基础 开发一类新的有针对性临床干预措施。