Peripheral-Nerve Allotransplantation in Rats Immunosuppressed with Transient or Long-Term FK-506

ABSTRACT

The purpose of this study was to assess regeneration across peripheral-nerve allografts by electro-physiologic methods, in rats receiving transient or long-term immunosuppression with FK-506. Lewis rats (LEW, RTl¹) were recipients of sciatic nerve isografts or allografts from donor LEW or ACI (RTl^a) rats, respectively. This latter donor-recipient inbred combination represents a major histoincompatible mismatch. The sciatic nerve was exposed through a gluteal muscle-splitting incision. A 2.0-cm segment of nerve was excised and a 2.5-cm graft sutured into the gap in epineural fashion. Seven groups (n = 8 each) included: Group 1-isograft control (LEW/LEW); Group 2-allograft control (LEW/ACI); Group 3-allografts receiving cyclo-sporin A (CsA) (10 mg/kg BW/day) subcutaneously for 2 weeks; Group 4-CsA for 2 weeks then biweekly subcutaneously; Group 5-FK-506 (10 mg/kg BW) intramuscularly by single injection; Group 6-FK-506 (1.0 mg/kg BW/day) for 2 weeks then biweekly intramuscularly; and Group 7-FK-506 for 2 weeks then biweekly intramuscularly. At 7 months, conduction velocities were determined and statistical analysis was performed. Excellent neural regeneration was observed in the isograft group (61.6 m/s), the allograft groups receiving long-term immunosuppression with either CsA (62.3 m/s) or FK-506 (61.7 m/s), and the transient FK-506 group (60.2 m/s). The transient CsA group (41.9 m/s), the allograft control group (53.4 m/s), and the single-dose FK-506 group (40.8 m/s) demonstrated significantly poorer results. Transient immunosuppression with FK-506 allowed for the restoration of anatomic and physiologic function of a peripheral-nerve allograft in inbred rats.