Dynamics of structural changes in sciatic nerve traction injury in rats: validation of a model for future preclinical studies on regenerative therapy

Traction injuries of peripheral nerves are morphologically similar to combat-related trauma, where the kinetic energy of a wounding projectile causes nerve stretching and irreversible microscopic and ultrastructural changes, while the anatomical integrity remains preserved. The study of such changes is of critical importance in the context of regenerative technologies, especially under wartime conditions. Aim. To assess morphological changes in the structure of peripheral nerves at different time points during recovery after experimental traction injury of the sciatic nerve in rats. Materials and methods. A traction injury model of the sciatic nerve was modeled in 26 white outbred rats using a modified device. Animals were divided into two experimental groups based on the observation period: 15 days and 30 days after injury, and a control group of sham-operated rats (30 days). Morphometric analysis was performed to evaluate the impact of traction on the morphofunctional state of nerve fibers in the proximal and distal segments of the injured sciatic nerve. The density of stromal and parenchymal cells in both nerve segments was assessed. Results. On day 15, the stroma/parenchyma ratio in the proximal segment of the sciatic nerve was 0.17 (0.155; 0.188), showing a statistically significant two-fold increase compared to the control group. In the distal segment, the ratio was 0.229 (0.206; 0.257), also representing a two-fold increase. No statistically significant difference was observed between the distal and proximal segments at this time point. By day 30, the stroma/parenchyma ratio in the proximal segment was 0.124 (0.096; 0.148), with no statistically significant difference compared to the control group or the 15-day proximal group. In contrast, the distal segment showed a ratio of 0.228 (0.215; 0.261), which was 2.7 times higher than in the control group and 1.8 times higher than in the proximal segment at the same time point. On day 15, endoneural accumulation of myelin breakdown products was observed, indicating active degenerative changes in nerve fibers. By day 30, a reduction in the number and size of myelin droplets in the distal segment, along with restored waviness and increased compactness of endoneural fibers, indicated stabilization of tissue architecture. However, persistent edema remained in the proximal segment, though signs of perineurial activation and a glio-mesodermal response suggested adaptive processes and the beginning of nerve trunk remodeling. Сonclusion. Morphological analysis revealed distinct stages of change in the peripheral nerve following traction injury. On day 15, signs of Wallerian degeneration, edema, inflammatory responses, and activation of stromal cells and fibroblasts were evident. By day 30, inflammation had decreased and partial restoration of nerve fiber structure was observed, although degenerative changes and the risk of fibrosis persisted. Understanding the morphogenesis of these structural changes may help justify the optimal timing and extent of surgical intervention, including the use of regenerative therapies.