Axotomy or compression is required for axonal sprouting following end-to-side neurorrhaphy.
End-to-side (ETS) nerve repair remains an area of intense scrutiny for peripheral nerve surgeon-scientists. In this technique, the transected end of an injured nerve, representing the "recipient" is sutured to the side of an uninjured "donor" nerve. Some works suggest that the recipient limb is repopulated with regenerating collateral axonal sprouts from the donor nerve that go on to form functional synapses. Significant, unresolved questions include whether the donor nerve needs to be injured to facilitate regeneration, and whether a single donor neuron is capable of projecting additional axons capable of differentially innervating disparate targets. We serially imaged living transgenic mice (n=66) expressing spectral variants of GFP in various neuronal subsets after undergoing previously described atraumatic, compressive, or epineurotomy forms of ETS repair (n=22 per group). To evaluate the source, and target innervation of these regenerating axons, nerve morphometry and retrograde labeling were further supplemented by confocal microscopy as well as Western blot analysis. Either compression or epineurotomy with inevitable axotomy were required to facilitate axonal regeneration into the recipient limb. Progressively more injurious models were associated with improved recipient nerve reinnervation (epineurotomy: 184+/-57.6 myelinated axons; compression: 78.9+/-13.8; atraumatic: 0), increased Schwann cell proliferation (epineurotomy: 72.2% increase; compression: 39% increase) and cAMP response-element binding protein expression at the expense of a net deficit in donor axon counts distal to the repair. These differences were manifest by 150 days, at which point quantitative evidence for pruning was obtained. We conclude that ETS repair relies upon injury to the donor nerve.
Hayashi
Ayato
A
Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, Campus Box 8238, 660 South Euclid Ave., St. Louis, MO 63110, USA.
Pannucci
Christopher
C
Moradzadeh
Arash
A
Kawamura
David
D
Magill
Christina
C
Hunter
Daniel A
DA
Tong
Alice Y
AY
Parsadanian
Alexander
A
Mackinnon
Susan E
SE
Myckatyn
Terence M
TM
D000818:Animals; D001369:Axons / Q000502:physiology*; D019771:Axotomy / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008866:Microsurgery / Q000379:methods; D009409:Nerve Crush / Q000379:methods*; D009416:Nerve Regeneration / Q000502:physiology*; D019635:Neurosurgical Procedures / Q000379:methods*; D016378:Tissue Transplantation / Q000379:methods