Effect of FK506 on subperineurial dejeneration after stripping of the Vasa nervorum; an ultrastructural and fuctional analysis

Several kinds of injury models, such as crush, transection, and graft repair have been well studied in terms of neuroprotective effect of FK506. However, definitive experimental studies are lacking on focal degeneration or ischemia. In the present study, our goal was to investigate the effect of FK506 on recovery of the sciatic nerve after focal ischemia produced by stripping of the epineurial vessels. A total number of 48 Wistar rats were used for this purpose and divided into four groups (control, sham-operated, FK506-treated, Vehicle-treated). Sciatic nerves were approached by femoral and gluteal muscle splitting. Then, epineural vessels around the sciatic nerve were stripped in the FK506-treated and Vehicle-treated groups. After operation, FK506 administration was performed from the first to the end of the forth postoperative week. Sciatic nerve regeneration was tested by walking track analysis, pinch test, light and electron microscopy. In the preoperative day, SFI values of the experimental group showed no significant difference (p>0.05) compared with the control group. However there was no statistical significance between FK506-treated and control group (p<0.05) in the 3rd and 4th postoperative week. In control and sham-operated groups, withdrawal responses to pinch were full (Grade 3). The onset day of full response (Grade 3) of withdrawal to pinch stimulation was in the 3rd postoperative week in six animals of the FK506-treated group. However, in the same postoperative week, six animals of the vehicle-treated group exhibited Grade 1, and four animals exhibited Grade 2 withdrawal response. So onset day of the withdrawal response in the vehicle-treated group was in the 4th postoperative week. Morphometric analysis revealed that there was no statistically difference between FK506 (+) and vehicle-treated groups by comparing the ratio of the degeneration area/total nerve area. It has been generally accepted that FK506 promotes nerve regeneration and enhances neurite outgrowth. However beneficial effect of the FK506 is generally based on the results on traumatic (crush, cut), and ischemic brain damages. In the present study we found that FK506 had a beneficial effect on focal degeneration produced by stripping of the epineurial vessels.Key words: sciatic nerve, vascular stripping, regeneration, FK506