American Society for Peripheral Nerve

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Brief Electrical Stimulation (ES) increases Axon Regeneration and Target Reinnervation after Delayed Peripheral Nerve Repair in a Sprague Dawley Rat Model
Kate Elzinga, MD1, Adil Ladak, MD, MSc2, Brandon Ball, MD3, Bohdan Savaryn1, Neil Tyreman1, Jaret Olson1 and Tessa Gordon1
1Department of Plastic Surgery, University of Alberta, Edmonton, Canada, 2Division of Plastic Surgery, University of Alberta, Edmonton, AB, Canada, 3Plastic and Reconstructive Surgery, University of Alberta, Edmonton, Canada

Introduction: Our findings of loss of regenerative capacity and Schwann cell (SC) support in rat models of delayed nerve repair account for clinical findings of poor functional recovery after nerve injuries. Brief 1h 20Hz electrical stimulation (ES) accelerates axon outgrowth after immediate nerve surgery in rats and, in patients after carpal tunnel release surgery, accelerates reinnervation of target muscles. The release surgery was conducted after delayed nerve damage, raising the possibility that ES can promote accelerate axon regeneration after delayed nerve repair. Objective: In this study we asked whether brief ES can promote axon regeneration after delayed nerve repair in a rat model as it does after immediate nerve repair. Methods: Under surgical anesthesia and aseptic conditions, the common peroneal (CP) or the tibial (TIB) nerve was transected and the two nerve stumps ligated and sutured to innervated muscle to prevent regeneration for 3m. Thereby injured CP neurons were prevented from reinnervating targets (chronic axotomy) or SCs were chronically denervated in the distal TIB nerve stumps. Following cross-anastomosis, the proximal CP nerve was subjected to 1h 20Hz ES or sham ES. Two and 4w later, retrograde fluororuby dye was applied to regenerating CP nerves within the distal TIB nerve 10mm from the suture site for enumeration of motor and sensory CP neurons that regenerated axons. In another group of rats 5m after cross-anastomosis of freshly cut CP to chronically denervated TIB nerve stump, numbers of motoneurons that reinnervated gastrocnemius muscle were estimated by the ratio of maximal and mean motor unit isometric twitch forces. Results: Significantly more 3m chronically axotomized CP motor and sensory neurons regenerated their axons 10mm into freshly denervated TIB nerve stumps 2 and 4w after cross-anastomosis and immediate 1h 20Hz ES than after sham ES treatment. There were also significantly more freshly axotomized CP neurons that regenerated axons 10mm into 3m chronically denervated TIB nerve stumps when these neurons were subjected to 1h 20Hz ES immediately after cross-anastomosis than when they were not. In a second group of rats significantly more motoneurons reinnervated gastrocnemius muscle 5m after cross-anastomosis and immediate ES than after the cross-anastomosis and sham ES. Discussion: Brief low frequency ES is effective in promoting axon regeneration and muscle reinnervation after delayed nerve repair. In light of evidence of ES induced neurotrophic factor expression, these data indicate that this expression may allow for axon regeneration to proceed more rigorously than without this re-expression.


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