gms | German Medical Science

Objectives/Interrogation: Cryopreservation and controlled freezing of the allograft nerve can decrease the immune response and graft rejection. Nerve allografts following discontinuous immunosuppression with FK506 also induced successful neuroregeneration with motor recovery following slight rejection and functional loss.

The purpose of this study was to evaluate efficacy of discontinuous FK506 administration on the axonal regeneration in a rat model after sciatic nerve reconstruction with allograft nerve pretreated with a cryopreservation.

Methods: Forty-eight Sprague-Dawledy rats were randomized into four groups (twelve rats per each group). In each group, had a unilateral 10-mm sciatic nerve gap repaired with an ipsilateral autologous graft (group I) and a cryo-preserved nerve allograft from 18 Lewis rat in the other three groups followed with low dose (0.1mg/kg) FK506 administration for 4 weeks (group II), 8 weeks (group III), and until sacrifice (group IV). At 12 weeks, motor nerve regeneration was evaluated on the basis of the ankle contracture, compound muscle action potential (CMAP), maximal isometric tetanic force (MITF), wet muscle weight of the tibialis anterior (TA) as well as histomorphometry and immunohistochemistry of the allograft nerve.

Results and Conclusions: MITF showed significantly lower functional recovery in Groups II and III treated with discontinuous FK506 administration after cryo-preserved nerve allograft compared Group I: 52.3 ± 10.3% for Group I, 31.7 ± 9.6% for Group II, 35.6 ± 8.6% forGroup III, and 41.7 ± 6.7% for Group IV compared to the contralateral side. Groups II and III were inferior to Group I regarding CMAP and the TA muscle weight (p < 0.05). There was no significant difference between the Group I and IV in terms of MITF and TA weight (p > 0.05). Histomorphometric analysis revealed that Groups II and III were inferior to Group I regarding Axon area, axon number, nerve fiber density (p < 0.05) and to Group IV regarding axon number (p = 0.001) (Table 2). Immunohistochemistry demonstrated that the morphology and distribution patterns of the axons in Group II and III showed less densely packed and little disorganized than Group I and IV.

In conclusion, withdrawal of immunosuppression resulted in graft rejection, a marked deterioration in function, and loss of regenerating fibers. A using cryo-preserved allograft nerves from cadaveric donors requires permanent immunomodulation for a valid surgical strategy to restore motor function of the damaged peripheral nerve.