Neurotrophins and their receptors in early axonal regeneration along muscle-vein-combined grafts

Experimental and clinical studies have shown that a vein segment filled with skeletal muscle used to bridge a peripheral nerve defect (muscle-vein-combined graft) leads to good nerve repair. However, the molecular basis of the nerve fiber regeneration process along this type of graft still remains to be elucidated. The aim of this study was to verify the expression of two neurotrophins, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), as well as their receptors, trkA and p75, in an early stage of axonal regeneration in muscle-vein-combined grafts. Severed rat sciatic nerves were repaired by means of 1-cm-long muscle-vein-combined grafts and withdrawn immediately after surgery (control grafts) and 5 days after surgery. Longitudinal sections of grafts were immunostained by means of the following antibodies: anti-NGF, anti-BDNF, anti-trkA, and anti-p75. An anti-glial fibrillar acid protein (anti-GFAP) antibody was used to recognize Schwann cells. Results showed the presence of a number of GFAP-positive Schwann cells inside the muscle-vein grafts. Many of these cells reacted for NGF, BDNF, and p75, but not trkA. In control grafts, i.e., immediately after surgery, no immunostaining was detected for any of the antibodies used in this study. These observations suggest that, very early after surgery, the muscle-vein-combined graft offers to growing axons an environment particularly favorable for regeneration, providing us with a possible explanation for the efficacy of this grafting technique for peripheral nerve repair.