Comparative dose-dependence study of FK506 on transected mouse sciatic nerve repaired by allograft or xenograft.
We evaluated the effects of FK506, at doses of 0.2, 2, and 5 mg/kg/day, on the response to nerve grafts implanted in outbred mice. A 6 mm long segment of the sciatic nerve was transected and repaired by autograft (the same segment resected), allograft (from another mouse), or xenograft (from a rat nerve). The regenerating nerves were harvested after 3 weeks and studied under light and electron microscope. Allografts of animals treated with the 5 mg/kg/day dose of FK506 appeared similar to those from autografts, demonstrating an equivalent number of myelinated fibers. In mice treated with the 2 mg/kg/day dose, regeneration was slightly hindered, as indicated by the reduced number of myelinated fibers. In contrast, in mice given a 0.2 mg/kg/day dose of FK506, allografts were not different from untreated allografts; both groups showed a marked rejection response with only few unmyelinated axons and no myelinated fibers. Xenografts showed a more severe rejection than allografts, with a marked inflammatory cell reaction throughout the graft. In contrast, in mice treated with the 5 mg/kg/day dose, xenografts exhibited a mild cell reaction and a greater number of regenerated myelinated fibers. In conclusion, effective axonal regeneration is achieved with FK506 administration at doses of 5 mg/kg/day through allografts and, partially, through xenografts.
Udina
Esther
E
Group of Neuroplasticity and Regeneration, Institute of Neurosciences and Department of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Voda
Jan
J
Gold
Bruce G
BG
Navarro
Xavier
X
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron / Q000295:instrumentation / Q000379:methods; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000637:transplantation / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D012584:Sciatic Nerve / Q000187:drug effects* / Q000293:injuries / Q000637:transplantation; D016559:Tacrolimus / Q000008:administration & dosage*; D014182:Transplantation, Autologous; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016559:Tacrolimus