Efficacy of delayed or discontinuous FK506 administrations on nerve regeneration in the rat sciatic nerve crush model: lack of evidence for a conditioning lesion-like effect.

We examined whether the nerve regenerative property of FK506 exhibits a 'window-of-opportunity' corresponding to the time of injury for maximal efficacy in the sciatic nerve crush model. FK506 (5 mg/kg, s.c.) was administered over the 18-day period of study according to three dosage regiments: delayed (days 9-17), discontinuous (days 0-8) and continuous (days 0-17) administrations. Quantitation of axonal calibers and the extend of myelination in the soleus nerve at 18 days demonstrated that both delayed and discontinuous administrations were equally effective, arguing against a 'window-of-opportunity' for FK506 nerve regenerative effect. However, both protocols were less effective than continuous administration indicating that the compound needs to be given during the entire regenerative period to elicit maximal efficacy.