Bimodal Activity of FK 506 (Tacrolimus): Low Dose FK 506-Application (0,1 mg/KG) with High Neurotrophic Effectiveness on Allogenous Nerve Transplants in Rats

Aim/Background: The development of nerve reconstruction procedures as an alternative to the present standard procedure of an autologous nerve transplantation is nowadays the focus of interest in clinical research of nerval regeneration. Despite of the neuro-regenerative effect of the immunosuppressive drug FK 506, the high doses used successfully up to now cannot justify the clinical application for nerval regeneration with regard to the side effects. Hence, the aim of this animal experimental study was to compare the neurotrophic effectiveness of a low dose FK 506 treatment on allogenous nerve transplants (allograft) with outcomes of autologous nerve transplants (isograft) to be able to estimate the valency concerning nerval regeneration. Material/Methods: The left sciatic nerve of rats of two strains (LEW and DA) was harvested at a distance of 1,5 cm. Nerve reconstruction consisted of nerve transplants between rats of the same strain (Isograft n=8) and between both strains (Allograft n=8) with FK 506- application (0,1 mg/KG). 8 rats underwent no operation and were served as an untreated control group. For the appraisal of a functional nerval regeneration analyses, the Sciatic Functional Index (SFI) and the Ankle Stance Angle (ASA) were carried out after 4, 8, 12 and 16 weeks post operationem. The histomorphometric evaluation consisted of the density of Myeln Basic Proteine (MBP) in immunohistochemically stained transversal semi- thin sections of the nerves of the experimental sides and of the non-operated sides after 16 weeks. Data of untreated animals served as references. Results: In all experimental groups nerval regeneration occurred. Superior histomorphometric and functional outcomes were seen in the group Allograft plus FK 506 (0.1 mg / kg). In this group the histomorphometric parameter and both functional parameters showed a significantly better nerve regeneration than in the Isograft group. Only in the group Allograft plus FK 506 (0.1 mg / kg) no significant differences to untreated animals were found histomorphometrically. Conclusion: With low dose of FK 506 a clear neuro-regenerative effect on Allograft nerve grafts appeared. Thereby it it possible to keep the side effects low with a high effectiveness of nerval regeneration with regard to a clinical application.