Ten Minutes of Electrical Stimulation Promotes Nerve Regeneration and Functional Recovery Following Nerve Transection and Repair in a Mouse Model
Junichi Sayanagi, MD1, Jesús A Acevedo-Cintron, BS1, Deng Pan, BS2, Lauren Schellhardt, BA1, Daniel A Hunter, RA3, Alison K Snyder-Warwick, MD4, Susan E Mackinnon, MD3 and Matthew D. Wood, PhD2, (1)Washington University School of Medicine, St. Louis, MO, (2)Washington University School of Medicine, St Louis, MO, (3)Department of Surgery, Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, Saint Louis, MO, (4)Washington University School of Medicine, Saint Louis, MO
Introduction: Despite expert surgical repair of severe nerve injuries, functional outcomes are often inadequate. Thus, strategies for improving treatments are being developed. Therapeutic electrical stimulation (ES) protocols using 60 minutes are one such promising technique reported to improve nerve regeneration and recovery after nerve repair. However, applying a 60 minute stimulation period during surgery increases operative time, cost, and potential complications. For clinical applications, it would be beneficial if shorter ES protocols were also effective as therapy. The purpose of this study was to examine if a 10-minute ES protocol improved nerve regeneration in a mouse sciatic nerve transection and repair model.
Materials & Methods: Male C57BL/6J mice were randomized to the following groups: 1) no ES, 2) 10 min ES and 3) 60 min ES. For all groups, the right sciatic nerve was transected 2mm proximal to the sciatic trifurcation and repaired immediately. In ES groups, a wire electrode was hooked around the sciatic nerve 2 mm proximal to the repair site, and ES (16 Hz, 0.5 mA, the minimum pulse width evoking a foot twitch) applied immediately following nerve repair. Following repair, the number of motoneurons regenerating axons was determined through retrograde tracking studies 1 week postoperatively. Histomorphological findings of repaired sciatic nerves were analyzed 2 weeks postoperatively. Motor and sensory function was evaluated by behavioral analysis using a grid walking test, von Frey filament test, and indirectly through muscle wet weight by 8 weeks postoperatively.
Results: Compared to the no ES group, 10 and 60 min ES groups showed significant increases in the number of motoneurons regenerating axons, myelinated axon counts, and combined weight of gastrocnemius and tibialis anterior muscles. Both ES groups also showed significant improvements in paw-withdrawal threshold and proportion of foot faults as measured in behavioral assays. There was no significant difference between 10 and 60 min ES groups in any measured outcomes.
Conclusions: A brief 10-minute ES protocol promoted nerve regeneration and functional recovery no different than a 60-minute ES protocol. This outcome provides potential to accelerate and expand clinical translation of ES to improve functional recovery for patients with peripheral nerve injury.
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