Delayed nerve repair is associated with diminished neuroenhancement by FK506.
OBJECTIVE
The immunosuppressive agent FK506 has been shown in many studies to enhance nerve regeneration and to accelerate functional recovery after immediate nerve repair. However, in clinical practice the diagnosis and treatment of patients with peripheral nerve injuries is often delayed. The study investigated whether FK506 would retain its neuroregenerative properties when nerve repair and initiation of FK506 therapy were delayed for 7 days.


METHODS
In vivo laboratory study.


METHODS
Thirty-two Lewis rats underwent tibial nerve transection and were randomly assigned to four experimental groups: immediate repair with FK506 treatment, immediate repair without FK506 treatment, 7-day delayed repair with FK506 treatment, and 7-day delayed repair without FK506 treatment. Treated animals received daily subcutaneous injections of 2 mg/kg FK506. Serial walking track measurements were performed at 14, 16, and 18 days after nerve repair. On day 18 after repair, peripheral nerves were injected with a fluorescent tracer for retrograde labeling. On day 21, peripheral nerves and spinal cords were harvested for histomorphometric analysis and motor neuron cell body counts, respectively.


RESULTS
Animals that underwent immediate repair with FK506 had significantly higher fiber counts and percentages of nerve than the other three groups (P <.05) but did not show statistically significant earlier functional recovery. The remaining three groups had intermediate levels of nerve regeneration that were not significantly different. Retrograde abled motor neurons counts were decreased in animals with delayed nerve repair that received no FK506 (P <.05).


CONCLUSIONS
In a rat tibial nerve transection model, the neuroregenerative effects of FK506 diminished markedly when repair and initiation of FK506 therapy were delayed by 7 days.
Brenner
Michael J
MJ
Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St Louis, Missouri, USA.
Fox
Ida K
IK
Kawamura
David H
DH
Yu
Vivian M
VM
Lowe
James B
JB
Hunter
Daniel A
DA
Mackinnon
Susan E
SE
D000704:Analysis of Variance; D000818:Animals; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D009416:Nerve Regeneration / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function; D016559:Tacrolimus / Q000494:pharmacology*; D013979:Tibial Nerve
D007166:Immunosuppressive Agents; D016559:Tacrolimus