Effects of Fkbp-12 Ligands Following Tibial Nerve Injury in Rats

The neuroregenerative properties of FK506, an FKBP-12 ligand that inhibits calcineurin, and V-10,367, an FKBP-12 ligand that does not inhibit calcineurin, were evaluated in crush and transection models. Rats were randomly assigned to one of seven groups, including untreated controls and FK506- or V-10,367-treated experimental groups. Following crush or transection nerve injury, animals were assessed with walking tracks, and histomorphometry. FK506-treated animals demonstrated significant functional recovery 11 days following crush and 18 days following transection injury. In untreated and V-10,367 treated animals, nerves recovered 13 days following crush injury, but did not improve significantly prior to sacrifice at 28 days in animals sustaining a transection injury. No statistically significant differences in histomorphometric parameters were identified between any of the groups. The study confirms that FK506 accelerates recovery from tibial nerve injury.