Article

The slow rate of nerve regeneration following injury can cause
extended muscle denervation, leading to irreversible muscle atrophy, fibrosis,
and destruction of motor endplates. The immunosuppressant FK506 (tacrolimus) has
been shown to accelerate the rate of nerve regeneration and functional recovery.
However, the toxic and immunosuppressive properties of FK506 make it undesirable
for long-term use. OBJECTIVE: To take advantage of the regeneration-enhancing
effects of FK506 but avoid the potential adverse effects of long-term
administration, the current study evaluates and quantifies the efficacy of
short-term FK506 treatment in rat models. METHODS: Clinically relevant
transection and graft models were evaluated, and walking track analysis (WTA) was
used to evaluate functional recovery. FK506 was administered for 5 and 10 days
post transection injury and 10 and 20 days post graft injury. Both groups
involving a short course were compared with the continuous administration group.
RESULTS: In the transection model, FK506 was administered for 5 and 10 days
postoperatively. WTA demonstrated that 10 days of FK506 administration was
sufficient to reduce functional recovery time by 29% compared with negative
controls. In the graft model, FK506 was administered for 10 and 20 days
postoperatively. Short treatment courses of 10 and 20 days reduced recovery time
by 15% and 21%, respectively, compared with negative controls. Analysis of
blood-nerve barrier (BNB) integrity demonstrated that FK506 facilitated early
reconstitution of the BNB. CONCLUSIONS: The results of this study indicate that
short-term FK506 delivery following nerve injury imparts a significant
therapeutic effect.

Langue : ANGLAIS