Abstract
Background
Nerve injuries of the upper extremity seldom regain full preinjury function. Delay in nerve repair, nerve gap and ischemic local conditions are some of the factors attributed as the cause. The proximal axonal segment regenerates in the presence of neuronotrophic factors present in nerve tissue. FK 506 and its nonimmunosuppressive analogues have been shown to influence the growth of axons experimentally. Parallel studies of animals and human beings have demonstrated strong, toxic effects of these agents.
Purpose
To review systematically data on the role of FK 506 and its analogues in peripheral nerve regeneration of randomized, controlled trials in rats. Reports dealing with the toxic effects of these agents all were reviewed as well.
Methods
Articles and reviews were identified through a computerized search of MEDLINE from January 1966 to September 1999 by using the terms “FK 506”, “FKBP-12 ligands”, “peripheral nerve regeneration” and “nephrotoxicity, cardiotoxicity and neurotoxicity in FK 506”. Two reviewers assessed the trials independently.
Results
FK 506 caused dose-related enhancement of axonal growth in all animals that were tested and for all routes of drug administration. Effects of FK 506 when used locally and of its analogues occurred in the same order as those of the parent drug.
Conclusions
FK 506 and its analogues have been experimentally proven to be potent nerve stimulators. Further studies are warranted in view of the pathological and clinical potential for nephrotoxicity and cardiotoxicity of these agents. The authors proposed an experimental model incorporating a nerve conduit filled with slow release FK 506 at the site of nerve gap or crush, thus decreasing its systemic effects.
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