Allografting combined with systemic FK506 produces greater functional recovery than conduit implantation in a rat model of sciatic nerve injury

Abstract

Implantation of allografts or nerve conduits has been used to promote regeneration following peripheral nerve injuries involving substantial axon loss. Both methods provide promising alternatives to autologous grafting and avoid donor site morbidity. We compared the relative efficacies of allografting versus conduit implantation in a rat model of sciatic nerve regeneration. Two rat strains (Lewis and Dark Agouti; n = 30) were employed. Unoperated animals served as controls (group I). Animals in groups II and III underwent left sciatic nerve resection over a distance of 15 mm; group II animals received implants of collagen type I conduits; and group III animals received allografts from the other rat strain and systemic low-dose (0.1 mg/kg/d) administration of FK506. Walking tracks were recorded after 4, 8, 12, and 16 weeks; nerve sections were stained for myelin basic protein after 16 weeks. Functional tests revealed significantly better recovery in group III animals compared with group II even though there was no significant difference in the extent of remyelination. Neither group achieved the functional or histomorphometric values of control animals. Improved functional recovery following allografting plus systemic FK506, in comparison with conduit implantation, underlines the importance of systemic administration of neurotrophic molecules for nerve regeneration.