Brachial plexus birth injury (BPBI) is one of the most common pediatric nerve injuries, occurring about 1 in every 1,000 births. Injury occurs due to excessive stretching to the head and neck during childbirth, causing damage to the brachial plexus nerve bundle, and frequently results in lifelong arm impairment. Disruptions to typical shoulder development have been reported, but when these disruptions occur or how they progress throughout development are less understood. Due to the rapid growth period when this injury occurs, the resulting nerve damage can substantially alter typical musculoskeletal development and function.

Injury location relative to the dorsal root ganglion also contributes to the differing sequelae and severity of limb deficits following BPBI. Nerve rupture occurring distal to the dorsal root ganglion (postganglionic) is associated with joint contracture, bone deformity, restricted longitudinal muscle growth, muscle spindle degeneration, and limb disuse. Nerve avulsion occurring proximal to the dorsal root ganglion (preganglionic) has some afferent sensory innervation preserved and is associated with less joint contracture and bony deformity, shorter and more atrophic muscles, and limb disuse. While these injury locations disrupt the brachial plexus in differing ways, their initial presentation is similar, which makes distinguishing them difficult and results in similar treatment plans.

Previous studies at 8-weeks after injury revealed bone alterations including worsened joint-level deformity following postganglionic injury, and worsened trabecular architecture in the scapula and humerus following preganglionic injury, and decreases in muscle mass following both injuries, and presence of fibrosis following both injuries in the biceps brachii and subscapularis muscles. Examining the effects of injury across a wider developmental timeline will provide a better understanding of when detriments develop and how they progress throughout skeletal development and maturation following BPBI.

Our overall aims were 1) to determine how passive muscle loading, active functional loading, and nerve injury following BPBI contribute to progressive alterations in glenohumeral microstructure and metabolism, and 2) to determine how three potential deformity drivers following BPBI affect underlying muscle structure and expression of myokines related to muscle growth and stimulation of bone metabolism. We utilized three surgical rodent models at a developmental stage similar to a human newborn that represent combinations of deformity drivers:​ postganglionic neurectomy results in denervation, muscle contracture, and limb disuse;​ preganglionic neurectomy results in denervation and limb disuse;​ and forelimb amputation represents limb disuse without BPBI. The objectives of this dissertation were to characterize changes to functional limb usage following BPBI, establish a timeline for development of microstructural bone deficits following BPBI and how these detriments progress through skeletal maturity, and understand cellular changes in both bone and muscle that occur following BPBI.

We observed that functional deficits in grip strength, gait, and paw preference were present by 6 weeks after injury and worsened over time for both post- and preganglionic injuries. Deficits in trabecular bone microstructure were present in the humerus by 2 weeks and in the scapula by 4 weeks after preganglionic injury. Trabecular deficits in the postganglionic humerus and scapula gradually worsened which accompanies gradual loss of function observed by 16- weeks. Muscle fibrosis was observed in the supraspinatus muscle in both postganglionic and preganglionic injuries and a timeline of how fibrosis presents and progresses in the biceps brachii, subscapularis, and supraspinatus muscles was established . This work provides valuable insight into how limb use is altered, how typical bone formation is disrupted, and how these disruptions progress with continued skeletal development following postganglionic and preganglionic BPBI Our findings provide critical information about how BPBI affects postnatal musculoskeletal development that may inform the type and timing of clinical treatments and rehabilitative therapies for future BPBI-related studies.