http://nnr.sagepub.com/content/26/6/570.abstract?etoc
Abstract
Background. 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.
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