Fawcett Emily B, Potts Jennifer R, Dixit Nikhil N, Saul Katherine R, Cole Jacqueline H
Lampe Joint Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, and North Carolina State University, Raleigh, NC, USA.
Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC, USA.
bioRxiv. 2025 May 27:2025.05.22.655603. doi: 10.1101/2025.05.22.655603.
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.
臂丛神经产伤（BPBI）是分娩困难时常见的神经损伤，此时臂丛神经束被过度拉伸，导致30%-40%的受影响者出现手臂功能障碍。损伤可出现在两个不同部位，在大鼠模型中分别模拟为节后和节前神经切除术。两种损伤类型都会出现骨畸形。然而，这些畸形背后的潜在因素尚未完全明确。虽然过去的研究探讨了肌肉结构和改变的机械关节负荷等因素，但骨代谢、肌肉组成以及肌肉-骨相互作用尚未得到充分研究。利用节后和节前BPBI大鼠模型以及废用模型，对骨代谢、肌肉组成和肌肉-骨相互作用进行了研究。采用动态组织形态计量学和类似方法来表征肱骨生长和肱骨生长板活性以了解骨代谢，分析肌肉纤维化以评估肌肉组成，并进行FGF-2定量以评估肌肉-骨相互作用。节后损伤在肱骨干区域的变化比节前更多，并且在骨内膜表面显示骨代谢降低，而节前损伤在骨膜表面显示骨代谢降低。然而，只有节前损伤显示生长板活性显著降低。关于纤维化，两种损伤类型在肱二头肌中均显示纤维化，但只有节前损伤在肩胛下肌中显示纤维化。肢体废用模型未显示纤维化。此外，节前损伤中FGF-2信号的产生增加，在肩胛下肌中更为明显。总体而言，节后损伤导致的畸形可能源于骨形成和骨吸收，而节前损伤导致的畸形可能源于骨生长的总体减少，而不仅仅是肢体废用。所观察到的纤维化和FGF-2信号改变不太可能是骨畸形的直接原因，并且节后和节前损伤之间改变背后的驱动因素可能不同。
