Long-term effects of muscle-derived protein with molecular mass of 77 kDa (MDP77) on nerve regeneration.

The long-term effects of the 77-kDa muscle-derived protein (MDP77) on motor and sensory nerve regeneration were examined in vivo. Fourteen-millimeter bridge grafts of the right sciatic nerve of SD rats were carried out with silicone tubes containing a solution of type I collagen together with 0, 5, 10, or 20 microg/ml recombinant human MDP77 (N = 10 in each group). Recovery of motor and sensory function was evaluated monthly by the maximal toe-spread index (TSI) and hot-plate test, respectively, for 6 months after the operation. Electrophysiology (nerve conduction velocity), histology (diameter and total number of the regenerated myelinated axons in the tube), and immunohistochemistry (total number of Schwann cells in the tube), as well as measurement of soleus muscle weight, were also performed at this time. Motor, but not sensory, function recovered rapidly in the MDP77-treated groups in a dose-dependent manner. Electrophysiological measurements and the ratio of soleus muscle weight corroborated the positive effects of MDP77 on motor nerve regeneration, but no facilitation of sensory nerve recovery was observed. Furthermore, histological and immunohistochemical evaluations suggested that MDP77 treatment accelerates Schwann cell migration, followed by enhanced maturation of regenerating axons, resulting in functional recovery of both the nerves and the atrophied, denervated muscle.