American Society for Peripheral Nerve

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A Rat Study Of The Use Of End-To-Side Peripheral Nerve Repair In Rats As A ‘Baby-Sitting’ Technique To Reduce The Deleterious Effect Of Chronic Denervation
Tessa Gordon, PhD1; Olewale AR Sulaiman, MD, PhD, FRCS2
1The Hospital for Sick Children, Toronto, ON, Canada, 2 Ochsner Neuroscience Institute, Tulane University, New Orleans, LA

Introduction: Functional recovery is disappointing after surgical repair of nerves injured far from their target organs and/or after delayed repair. In the former case, a nerve transfer of a transected distal nerve fascicle to innervate denervated targets is one strategy to promote nerve regeneration and functional recovery. An alternate strategy tested here is to perform an end-to-side neurorrhaphy (end-to-sideN) to 'baby-sit' (protect) the denervated distal nerve stump at the time of nerve repair in order to reduce the deleterious effect of chronic denervation on nerve regeneration.

Materials & Methods: In Sprague-Dawley rat hindlimbs, the common peroneal (CP) nerve was transected unilaterally and the CP distal stump inserted through a perineurial window into the intact tibial (TIB) nerve-CP end-to-sideN. In experimental set #1, TIB motoneurons that regenerated and/or sprouted axons into the CP nerve within three months were stimulated to elicit contractions and thereafter backlabelled with retrograde dyes for counting. In experimental set #2, the intact TIB nerve was transected and cross-sutured to a three month chronically denervated CP distal nerve stump that had been either 'protected' by ingrown TIB nerves after the CP-TIB end-to-sideN or had remained chronically denervated. Thereafter numbers of retrogradely labelled TIB motoneurons that had regenerated their axons within three months were counted and reinnervated tibialis anterior (TA) muscles weighed.

Results: A mean (+ SE) of 231 + 83 TIB motoneurons grew into the end-to-side CP distal nerve stump with corresponding ankle flexion; 32% regenerated their axons and 24% sprouted axons from intact TIB nerve eliciting ankle flexor-extensor co-contraction. In the experimental set #2 after a three month period of TIB nerve regeneration, significantly more TIB motoneurons regenerated axons into 'protected' and 'unprotected' CP distal nerve stumps (cf. mean numbers of 332 + 43.6 and 235 + 39.3) with corresponding and significantly higher numbers of regenerated nerve fibers and in turn, significantly better recovery of reinnervated TA muscle weight.

Conclusions: Our experiments demonstrated that delayed nerve repair is more effective when the deleterious effects of chronic denervation of the distal nerve stump are reduced by protecting the stump with ingrowing nerve fibers across an end-to-side insertion of the distal nerve stump into a neighboring intact nerve. Such an end-to-sideN may be invaluable, reducing atrophy of distal nerve stumps and target organs after chronic denervation and in turn, allowing for effective reinnervation of the protected distal nerve stumps and target organs over distance and time.

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