Brief Electrical Stimulation of the Distal and Proximal Sciatic Nerve During Transection and Repair in a Mouse Model

Introduction/Aims: Therapeutic electrical stimulation (ES) of repaired nerves has been demonstrated to improve muscle function. Previous studies applied ES to the proximal transected nerve end (P-ES) with benefits to the neuronal cell body. We investigated whether a single ES dose applied to the distal end (D-ES) or distal and proximal ends (DP-ES) prior to nerve repair provides benefits to neuromuscular junction (NMJ) and muscle recovery. Methods: S100-GFP mice were randomized to control (No ES), D-ES, P-ES, and DP-ES groups. After sciatic nerve transection, the ES groups received 10 min of ES prior to repair. The non-stimulated nerve end was insulated with a rubberized wrap. At 3 and 4 weeks post-repair, analyses using tetanic muscle force, grid walking, and NMJ immunohistochemistry were performed. Results: Muscle force demonstrated D-ES, P-ES, and DP-ES significantly improved muscle function at 4 weeks compared to No ES. Grid-walking tests showed significantly fewer foot faults in D-ES and DP-ES mice. Mice treated with ES showed higher NMJ innervation compared to No ES. In addition, the number of terminal Schwann cells (tSCs) and the percentage of NMJs with tSC sprouting beyond the NMJ area were significantly higher in ES groups, indicating improved innervation. Endplate morphology was similar among ES groups. Discussion: In addition to known benefits of P-ES, D-ES and P-ES demonstrated beneficial effects for reinnervation and muscle function post-nerve injury. While the mechanism is not fully characterized, ES applied to both D-ES and P-ES aspects of a transected nerve may act synergistically to improve muscle healing.