Efectes de l’FK506 en la regeneració després de reseccions

We compared the effects of FK506 administration on regeneration and reinnervation after sciatic nerve resection and repair with an autologous graft or with a silicone tube leaving a 6-mm gap in the mouse. Functional reinnervation was assessed by noninvasive methods to determine recovery of motor, sensory, and sweating functions in the hindpaw over 4 months after operation. Morphometric analysis of the regenerated nerves was performed at the end of follow-up. The nerve graft allowed for faster and higher levels of reinnervation in the four functions tested than silicone tube repair. Treatment with FK506 (for the first 9 weeks only) resulted in a slight, although not significant, improvement of the onset of reinnervation and of the maximal degree of recovery achieved after autografting. The recovery of pain sensibility and of the compound nerve action potentials in the digital nerves, which directly depend on axonal regeneration, showed better progression with FK506 than reinnervation of muscles and sweat glands, which require reestablishment of synaptic contacts with target cells. The myelinated fibers in the regenerated nerve showed a more mature appearance in the FK506-treated rats. However, FK506 showed a marginal effect in situations in which regeneration was limited, as in a silicone tube bridging a 6-mm gap in the mouse sciatic nerve. In conclusion, treatment with FK506 improved the rate of functional recovery after nerve resection and autograft repair. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 905–915, 2001 EFFECTS OF FK506 ON NERVE REGENERATION AND REINNERVATION AFTER GRAFT OR TUBE REPAIR OF LONG NERVE GAPS XAVIER NAVARRO, MD, PhD, ESTHER UDINA, MD, DOLORES CEBALLOS, PhD, and BRUCE G. GOLD, PhD Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Spain Center for Research on Occupational & Environmental Toxicology and Department of Cell & Developmental Biology, Oregon Health Sciences University, Portland, Oregon, USA Accepted 26 January 2001 Following severe peripheral nerve injuries resulting in loss of continuity and an interstump gap, the preferred method of repair consists of autologous nerve grafting. The use of an autologous graft has some disadvantages, such as the need of a second surgical step, loss of donor nerve function, limited supply of donor nerves, and the mismatch between nerve and grafts. The use of nerve allografts has not been encouraging because regeneration is low or absent due to immunological rejection. Immunosuppressive therapy is needed to prevent graft rejection, but its secondary complications (e.g., nephrotoxicity) usually overcome the benefits, and rejection occurs after discontinuation of immunosuppression with deleterious effects on the regenerated axons and the functional recovery achieved. Tubulization (the implantation of a biocompatible nerve guide to bridge the gap) is an alternative to the repair of transected nerves. Tube repair provides physical guidance to the regenerating axons, prevents axonal escape into the surrounding tissues, and creates a local microenvironment whereby trophic factors from the injured nerve may become concentrated and facilitate axonal growth. However, the success of Abbreviations: AG, autologous graft; CMAP, compound muscle action potential; CNAP, compound nerve action potential; dpo, day postoperation; FK, FK506; FKBP, FK506 binding protein; FRI, functional recovery index; PP, pinprick test; SFI, sciatic functional index; SG, sweat gland; SIL, silicone tube