End-to-side neurorrhaphy: evaluation of axonal response and upregulation of IGF-I and IGF-II in a non-injury model.
This research group has introduced a model of end-to-side neurorrhaphy, in which reinnervation occurs without frank damage to donor axons. The current study used in situ hybridization to test the hypothesis that insulin-like growth factor (IGF-I and IGF-II) mRNA levels increase at the coaptation site and grafted nerve following end-to-side repair, and that this increase is associated with axonal sprouting and growth. One week after end-to-side coaptation, IGF-I mRNA was localized predominantly on the epineurial side of the graft perineurium, while IGF-II was seen mainly on the endoneurial side. IGF-I hybridization was greatest at this time and declined by 2 weeks post-procedure. No changes in IGF mRNA levels occurred in the distal donor nerve. The increase in IGF-I mRNA at 1 week preceded the appearance of myelinated axons. The presence of myelinated axons within the graft 2 weeks after end-to-side coaptation was associated with a decline in IGF-I mRNA. These data are the first to demonstrate increased IGF mRNA levels associated with axonal sprouting and growth following end-to-side neurorrhaphy. Moreover, the findings support those of earlier studies by others implicating IGFs in axonal regeneration. The increase in IGF mRNA during sprouting and axonal growth into an end-to-side coaptation indicates that the local therapeutic augmentation of endogenous IGF levels at the coaptation site may enhance axonal sprouting from a minimally injured donor nerve, and thereby increase the number of axons that reinnervate the graft.
Fortes
W M
WM
Microsurgical Research Center, International Institute of Reconstructive Microsurgery, Department of Surgery, Eastern Virginia Medical School, Norfolk 23507, USA.
Noah
E M
EM
Liuzzi
F J
FJ
Terzis
J K
JK
D000714:Anastomosis, Surgical; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D004195:Disease Models, Animal; D005260:Female; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D019635:Neurosurgical Procedures / Q000379:methods*; D010784:Photomicrography; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012584:Sciatic Nerve / Q000473:pathology / Q000601:surgery*; D016378:Tissue Transplantation / Q000379:methods; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II