Neuroregenerative effects of preinjury FK-506 administration.
BACKGROUND
FK-506 is used in organ transplantation because it promotes neurite outgrowth in vitro and enhances neuroregeneration in peripheral nerve injury transection models. Immunosuppressive mechanisms of FK-506 are well defined, with demonstration of decreased neuroregenerative effects with delayed administration. The purpose of this study was to describe the effects of preinjury administration of FK-506 in rats with tibial nerve transection injury.


METHODS
Eight inbred male Lewis rats per group in three separate groups underwent tibial nerve transection with primary repair. Group I received placebo, group II received FK-506 treatment at 1 day before surgery, and group III received FK-506 preloading 3 days before surgery.


RESULTS
Histologic and histomorphometric results demonstrated the preload FK-506 group had superior results compared with the immediate FK-506 group. Both FK-506 groups were superior to the placebo group. The preload FK-506 demonstrated superior regeneration in mean total nerve fiber counts (p < 0.05), greater percentage neural tissue (p < 0.05), greater mean nerve fiber density (p < 0.05), and lower percentage of debris (p > 0.05). Mean nerve fiber widths were similar in the preload and immediate FK-506 groups but superior to the placebo group.


CONCLUSIONS
These data suggest that enhancement of FK-506's neuroregenerative effect is enhanced when administered before nerve injury such as when performing elective surgery.
Snyder
Alison K
AK
Division of Plastic and Reconstructive Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Mo. 63110, USA.
Fox
Ida K
IK
Nichols
Chris M
CM
Rickman
Susan R
SR
Hunter
Daniel A
DA
Tung
Thomas H H
TH
Mackinnon
Susan E
SE
D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects*; D019635:Neurosurgical Procedures; D018373:Peripheral Nervous System Agents / Q000494:pharmacology*; D011300:Preoperative Care; D051381:Rats; D011917:Rats, Inbred Lew; D016559:Tacrolimus / Q000494:pharmacology*; D013979:Tibial Nerve / Q000187:drug effects* / Q000293:injuries / Q000473:pathology / Q000601:surgery; D020196:Trauma, Nervous System / Q000188:drug therapy* / Q000628:therapy
D018373:Peripheral Nervous System Agents; D016559:Tacrolimus