title: Side-to-side nerve grafts sustain chronically denervated peripheral nerve pathways during axon regeneration and result in improved functional reinnervation.
abstract: BACKGROUND
  Progressive atrophy of Schwann cells in denervated nerve stumps is a major reason for progressive failure of functional recovery after peripheral nerve injury and surgical repair.
  
  
  OBJECTIVE
  To examine whether side-to-side nerve bridges between an intact donor nerve and a recipient denervated distal nerve stump promote nerve growth and in turn, protect distal nerve stumps to improve axon regeneration after delayed surgical repair.
  
  
  METHODS
  In Sprague-Dawley rats, 1 or 3 side-to-side common peroneal (CP) nerve bridges were used to bridge between the donor intact tibial (TIB) nerve and a recipient denervated CP distal nerve stump in the contralateral hind limb. No bridges were placed in control animals. After 4 months, either a fluorescent retrograde dye was applied to back-label TIB motoneurons with axons that had grown into the CP nerve stump or the proximal and distal CP nerve stumps were resutured in experimental and control animals to encourage CP nerve regeneration for 5 months. Retrograde dyes were again applied to count CP motoneurons that regenerated their axons through protected and unprotected nerve stumps.
  
  
  RESULTS
  Significantly more donor TIB motoneurons regenerated axons into the recipient denervated CP nerve stump through 3 side-to-side CP nerve bridges compared with 1 bridge. This TIB nerve protection significantly increased the number of CP motoneurons regenerating axons through the denervated CP nerve stumps, the number of regenerated axons, and the weight of the reinnervated muscles.
  
  
  CONCLUSIONS
  Multiple side-to-side nerve bridges protect chronically denervated nerve stumps to improve axon regeneration and target reinnervation after delayed nerve repair.
authors.affiliation: Division of Plastic Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Adil
authors.initials: A
authors.lastname: Ladak
authors.forename: Paul
authors.initials: P
authors.lastname: Schembri
authors.forename: Jaret
authors.initials: J
authors.lastname: Olson
authors.forename: Esther
authors.initials: E
authors.lastname: Udina
authors.forename: Neil
authors.initials: N
authors.lastname: Tyreman
authors.forename: Tessa
authors.initials: T
authors.lastname: Gordon
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D005260:Female; D006614:Hindlimb / Q000294:innervation / Q000601:surgery; D009416:Nerve Regeneration / Q000502:physiology*; D016067:Nerve Transfer / Q000379:methods*; D010543:Peroneal Nerve / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013979:Tibial Nerve / Q000293:injuries / Q000601:surgery