Biology subjects

Saul, K. R.

Publications and source records attributed to Saul, K. R..

4 recordsLinked to original sources

bioRxiv2025

Brachial Plexus Birth Injury Causes Location-Dependent Detriments in Glenohumeral Trabecular Bone Microstructure

Brachial plexus birth injury (BPBI) is caused during a difficult childbirth when the head and neck are excessively stretched, and the brachial plexus nerve bundle is damaged. Injury causes lifelong arm impairment in 30-40% of those affected, but the extent to which bone microstructure is affected and how that relates to bone morphology alterations is unclear. Additionally, how injury location impacts trabecular bone, and the role limb disuse plays in these differential effects are unknown. Using two rat models of BPBI (postganglionic and preganglionic) and a disuse model (disarticulation), trabecular bone microstructure and glenohumeral morphology were characterized in the proximal humerus and distal scapula. For bone microstructure, the regions closest to the joint articulating surface incurred the greatest detriments with the least robust trabecular bone. These trabecular bone deficits in the humeral epiphysis and scapular neck were greater following preganglionic injury than postganglionic injury. The effects in the disarticulation group tended to align more with those in the postganglionic group, and greater detriments were observed in the scapula than in the humerus. Bone morphology metrics were explained mainly by quantity and architecture of trabecular bone but were not explained by the same metrics across all groups. Combining results with changes in bone morphology, data suggest differential effects with injury location and the effects of limb disuse to be most prominent in the postganglionic injury group and the distal scapula. In addition, the differences in results between postganglionic and preganglionic and macrostructural and microstructural deformity, suggest different drivers for postganglionic and preganglionic injuries and different factors causing macrostructural and microstructural alterations.

bioengineering↗

bioRxiv2025

Bone Mineralization and Metabolism are Altered in a Rat Model of Brachial Plexus Birth Injury

Brachial plexus birth injury (BPBI) is a common nerve injury incurred during a difficult childbirth when the brachial plexus nerve bundle is excessively stretched, resulting in functional arm impairment in 30-40% of those affected. Injury can present in two different locations, modeled in rats as postganglionic and preganglionic neurectomies. Osseous deformities are present following both injury types. However, the underlying factors behind these deformities are not fully understood. While past studies have explored muscle structure and altered mechanical joint loading as factors, bone metabolism, muscle composition, and muscle-bone crosstalk have not been fully explored. Using postganglionic and preganglionic BPBI rat models and a disuse model, bone metabolism, muscle composition, and muscle-bone crosstalk were explored. Dynamic histomorphometry and similar methods were used to characterize humeral growth and humeral growth plate activity to understand bone metabolism, muscle fibrosis was analyzed to assess muscle composition, and FGF-2 quantification was performed to assess muscle-bone crosstalk. Postganglionic injury portrayed more changes in the humeral diaphyseal region than preganglionic and displayed reduced bone metabolism on the endosteal surface while preganglionic displayed reduced bone metabolism on the periosteal surface. However, only preganglionic showed significantly lower growth plate activity. In regards to fibrosis, both injury types showed fibrosis in the biceps but only preganglionic showed fibrosis in the subscapularis. The limb disuse model did not show fibrosis. Additionally, preganglionic had an increased production of FGF-2 signaling more so in the subscapularis. Overall, deformities from postganglionic injury may be from bone formation and bone resorption while deformities from preganglionic injury are likely from an overall reduction in bone growth that is not solely from limb disuse. The fibrosis and FGF-2 signaling alterations seen are not likely to be the direct cause of osseous deformity and the drivers behind the alterations are likely different between postganglionic and preganglionic injuries.

bioengineering↗

bioRxiv2020

Characterizing Trabecular Bone Properties near the Glenohumeral Joint Following Brachial Plexus Birth Injury

Brachial plexus birth injury (BPBI) causes functional arm impairment in 30-40% of those affected due to altered loading on the glenohumeral joint. While gross morphological osseous deformities have been seen in the humerus and scapula, alterations in the underlying trabecular bone microstructure and mineralization are not clear. Using a murine model of BPBI, trabecular bone alterations were explored in the proximal humerus and distal scapula, which surround the articulating surface of the joint. Samples were scanned using micro-CT, reoriented, and analyzed for standard trabecular metrics. The regions of interest closest to the articulating surface showed the greatest detriments. In the scapula, the scapular neck region showed less robust trabecular bone in the neurectomy group with decreased BV/TV (p=0.001), BMD (p=0.001), Conn.D (p=0.006), Tb.N (p<0.0001), and DA (p=0.033), and increased Tb.Sp (p<0.0001) compared to sham. In the humerus, the epiphysis showed less robust trabecular bone in neurectomy group, but to a much lesser extent than the scapular neck. The neurectomy group showed reduced BMD (p=0.007) and Tb.N (p=0.029) compared to sham. Data suggest deformities are worse near the articulating surface, likely due to the greater amount of mechanical loading. The reduction in trabecular microstructure and mineralization may compromise bone strength of the affected limb following BPBI. Further investigation of the underlying trabecular bone deformities following injury are necessary to eventually inform better treatments to limit the development of deformities.

bioengineering↗

bioRxiv2020

Forelimb unloading impairs glenohumeral muscle development in growing rats

Proper joint loading is essential for healthy musculoskeletal development. Many pediatric neuromuscular disorders cause irreversible muscle impairments resulting from both physiological changes and mechanical unloading of the joint. While previous studies have examined the effects of hindlimb unloading on musculoskeletal development in the lower limb, none have examined solely forelimb unloading. Thus, a large deficit in knowledge of the effect of upper limb unloading exists and must be addressed in order to better understand how the glenohumeral joint adapts during development. Two forelimb unloading models were developed to study the effects of varying degrees of unloading on the glenohumeral joint in growing rats: forelimb suspension (n=6, intervention 21 days post-natal) with complete unloading of both limbs via a novel suspension system and forearm amputation (n=8, intervention 3-6 days post-natal) with decreased loading and limb use in one limb after below-elbow amputation. After 8 weeks of unloading, changes in muscle architecture and composition were examined in ten muscles surrounding the shoulder. Results were compared to control rats from a previous study (n=8). Both methods of altered loading significantly affected muscle mass, sarcomere length, and optimal muscle length compared to control rats, with the biceps long head and triceps long head observing the most marked differences. Forearm amputation also significantly affected muscle mass, sarcomere length, and optimal muscle length in the affected limb relative to the contralateral limb. Muscle composition, assessed by collagen content, remained unchanged in all groups. This study demonstrated that forearm amputation, which was administered closer to birth, had greater effects on muscle than forelimb suspension, which was administered a few weeks later than amputation.

bioengineering↗