Histopathological and immunohistochemical evaluation of the effect of tacrolimus on nerve regeneration following crushed sciatic nerve in mice

Studies have been conducted to find effective agents for nerve regeneration. The present study was conducted on sixteen adult male Syrian mice with the aim of assessment of the effects of tacrolimus on crushed sciatic nerve injury and its comparison with spontaneous repair. After exposure of the left sciatic nerve, crushing was performed using a 2 mm wide mosquito hemostatic forceps tip for 10 seconds. Animals were randomized into two groups of treatment group (Group I), and the control (Group II) with eight mice each. The treatment group received tacrolimus (5 mg/kg, q24h, SC) until the end of the study, and the control group received no therapeutic agents. Histopathological and immunohistochemical assessment was performed on second and fourth post-operative weeks, and suggested that perineurium formation did not show a significant difference between the study groups (p>0.05). At the end of the second week in the treatment group, the reduction of axon inflammation and swelling, and the increase in axonal count showed a significant difference with the control group (p<0.05).  At the end of the fourth week, the difference in inflammation severity between the groups was not significant (p>0.05) but the decrease in axonal swelling and increase in axonal count in the treatment group showed a significant difference with the control group (p<0.05).  Increase of glial fibrillary acidic protein (GFAP) expression showed significant difference between the treatment group and the control group at the end of the study (p<0.05). Based on the present results, the use of tacrolimus was responsible for reduction of inflammation in a two week period, and at the end of the fourth week, increase of axonal count and edema suppression caused regeneration of injured nerve.