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: 10862979
• 负责人: Anita Singh
• 金额: $ 45.37万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 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 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10862979
• 关键词: 3-Dimensional; 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; Vertebral column; Visualization software; Work; avulsion injury; biochemical model; clinical development; clinical diagnostics; clinical training; clinically relevant; combinatorial; delivery complications; 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; neuronal excitability; next generation; novel; porcine model; predictive modeling; predictive tools; pressure; prevent; primipara; response; risk prediction; severe injury; simulation; tool; transmission process; 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）是分娩并发症，可导致显著的长期