Axonal regeneration after cold preservation of nerve allografts and immunosuppression with tacrolimus in mice

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Abstract
Object. The purpose of this study was to combine the immunosuppressive and neuroregenerative effects of tacrolimus (FK506) with cold preservation of peripheral nerve allografts to maximize axonal regeneration across short peripheral nerve gaps. Methods. Ninety-six male C3H mice were randomized to six groups, which were composed of animals with isografts (Group 1, positive control), allografts (Group 2, negative control), allografts treated with subtherapeutic doses of FK506 without and with cold preservation (Groups 3 and 4), and allografts treated with therapeutic doses of FK506 without and with cold preservation (Groups 5 and 6). Results were determined using walking-track data and histomorphometric measurements. Three weeks postoperatively, animals treated with therapeutic doses of FK506 after receiving cold-preserved allografts demonstrated accelerated functional recovery relative to all other groups. In addition, histomorphometric parameters in these animals (1257 ± 847 total axons, 6.7 ± 3.3% nerve tissue, 11.8 ± 6.5% neural debris, 8844 ± 4325 fibers/mm2 nerve density, and 2.53 ± 0.25 µm fiber width) were the same as or better than in all other groups. The parameters of percent nerve tissue (p < 0.016), nerve density (p < 0.038), and percent neural debris (p < 0.01) were statistically significantly better than those in all other groups, including Group 1 (isograft, positive control). Conclusions. The combination of FK506 treatment with cold preservation of nerve allografts resulted in functional and histomorphometric recovery superior to that with either modality alone.