Development and Persistence of Tissue-Level Musculoskeletal Deformity Following Brachial Plexus Birth Injury

臂丛神经出生损伤后组织水平肌肉骨骼畸形的发展和持续

• 批准号: 10838188
• 负责人: Jacqueline H Cole
• 金额: $ 7.99万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10838188
• 关键词: Affect; Animals; Articular Range of Motion; Biological; Birth trauma; Bone Density; Bone Injury; Brachial plexus structure; Characteristics; Clinical Treatment; Computer Models; Computer Simulation; Contracture; Data; Deformity; Development; Elements; Environment; Gait; Growth; Image; Impairment; Injury; Intervention; Joint structure of shoulder region; Limb Development; Limb structure; Location; Mechanics; Methods; Modeling; Morphology; Motion; Muscle; Musculoskeletal; Paralysed; Parents; Pattern; Property; Rattus; Research; Running; Structure; Surgical Disarticulation; Time; Tissues; Upper Extremity; Walking; Work; arm; bone; experience; humerus; insight; microCT; neuromuscular; parent grant; placebo group; postnatal period; response; scapula; spatiotemporal; timeline; tissue stress

Project Summary Brachial Plexus Birth Injury (BPBI) is a neuromuscular injury that causes lifelong arm impairments and deformities in the glenohumeral joint which restricts mobility of the upper limb. Little is known about the progression of bone and muscle growth in the postnatal period following BPBI. The parent grant explores key drivers of deformity progression including the timeline of development and resultant functional effects through a rat model consisting of different injury locations and unloading (preganglionic and postganglionic neurectomy, disarticulation, and sham groups). The primary hypothesis is that the key driver in BPBI bone deformity is the mechanical environment due to impaired longitudinal growth of paralyzed muscle and altered active functional loading beginning shortly after injury. The proposed work will further the parent research by investigating active loading of the glenohumeral joint during functional gait in a rat model. Bone readily adapts to its mechanical environment, so analysis of its organized microstructures would also provide insight to key mechanical drivers of microstructural deficits. Supplement Aim 1. Determine how limb loading is altered during functional gait following BPBI. Rationale: Spatiotemporal characteristics of gait are substantially and differentially altered during walking in rats following pre- and postganglionic neurectomy. However, the forces experienced on each limb at the ground and on the developing glenohumeral joint are unknown and are likely important drivers of glenohumeral development. Supplement Aim 2. Determine how active limb loading during functional gait drives morphological and microstructural changes in the glenoid. Rationale: Our unique co-simulation computational model of glenohumeral growth and function has been used to directly relate specific deformity and contracture features to isolated changes in passive muscle force, active range of motion, and biological growth rate; however, actual limb usage and its mechanical relationship to bone material properties and trabecular organization has not yet been explored. Altered gait and limb loading during walking and running after neurectomy will be evaluated to explore how limb usage and loading is affected by BPBI. Spatiotemporal motion data and ground contact forces will be recorded for each animal and compared among groups. Resultant gait data will be integrated into the computational simulation of glenohumeral loading and adaptation during active limb function following BPBI. Tissue properties will be validated using micro-computed tomography (micro-CT) images of the internal bone density and microstructure of the scapula and humerus collected under the R01 project and used to identify the portion of bone response due to active loading. A micro-CT-based micro-scale finite element model will provide tissue stress and yielding patterns to elucidate loading-driven adaptations in trabecular organization. The proposed supplement work will advance the originally planned modeling approach by including dynamic limb loads and new methods to actively predict bone material property changes and trabecular organization adaptations over the time of limb development.

项目概要 臂丛神经出生损伤 (BPBI) 是一种神经肌肉损伤，会导致终身手臂损伤和 盂肱关节畸形，限制上肢活动。人们对此知之甚少 BPBI 后产后骨骼和肌肉生长的进展。家长补助金探索关键 畸形进展的驱动因素，包括发育时间线和由此产生的功能影响 由不同损伤部位和卸载组成的大鼠模型（节前和节后神经切除术， 离断组和假组）。主要假设是 BPBI 骨畸形的关键驱动因素是 由于瘫痪肌肉的纵向生长受损和主动功能改变而导致的机械环境 受伤后不久就开始负重。拟议的工作将通过调查积极的研究来进一步推进家长研究 大鼠模型功能性步态期间盂肱关节的负荷。骨骼很容易适应其力学 环境，因此对其有组织的微观结构的分析也将提供对关键机械驱动因素的洞察 微观结构缺陷。补充目标 1. 确定功能步态期间肢体负荷如何变化 遵循 BPBI。理由：步态的时空特征发生了显着且差异性的改变 节前和节后神经切除术后大鼠行走期间。然而，每个人所经历的力量 地面上的肢体和发育中的盂肱关节是未知的，并且可能是重要的驱动因素 盂肱发育。补充目标 2. 确定功能性步态期间的主动肢体负荷 驱动关节盂的形态和微观结构变化。理由：我们独特的联合仿真 盂肱生长和功能的计算模型已用于直接关联特定的畸形 和挛缩特征到被动肌力、主动运动范围和生物的孤立变化 增长率;然而，实际肢体的使用及其与骨材料特性的机械关系和 小梁组织尚未被探索。步行和跑步期间的步态和肢体负荷改变 将评估神经切除术，以探讨 BPBI 对肢体使用和负荷的影响。时空运动 将记录每只动物的数据和地面接触力并在各组之间进行比较。结果步态 数据将被整合到活动期间盂肱负荷和适应的计算模拟中 BPBI 后的肢体功能。将使用微型计算机断层扫描 (micro-CT) 验证组织特性 R01下采集的肩胛骨和肱骨的内部骨密度和显微结构图像 项目并用于识别由于主动负载而引起的骨骼响应部分。基于显微CT的微型尺度 有限元模型将提供组织应力和屈服模式，以阐明负载驱动的适应 小梁组织。拟议的补充工作将推进原计划的建模方法 通过包括动态肢体负载和新方法来主动预测骨材料特性的变化和 随着肢体发育时间的推移，小梁组织发生适应性变化。