4-METHYLCATECHOL, AN INDUCER OF NERVE GROWTH-FACTOR SYNTHESIS, ENHANCES PERIPHERAL-NERVE REGENERATION ACROSS NERVE GAPS

The effect on peripheral nerve regeneration of 4-methylcatechol (MC), which is a potent inducer of nerve growth factor (NGF) synthesis in vi tro and in vivo, was examined in a sciatic nerve-lesioned animal model , The sciatic nerve of adult male Wistar rats was transected and both of the cut ends were then inserted into sterile silicone tubes that we re subsequently attached to an intervening silicone chamber. After sur gery, the rats were injected i.p. every day for 2 weeks with MC. Two w eeks after surgery, the density of nonmyelinated axons within the cham ber was significantly increased in the MC-treated group compared with that in the control group. Five weeks after surgery, both the number a nd the diameter of myelinated axons within the chamber of the MC-treat ed group were significantly larger than those of the control group. Wh en the chamber was filled with anti-NGF antibody solution, most of the MC effect was blocked. These results suggest that MC stimulates de no vo synthesis of NGF (and/or NGF-related molecules), which results in t he enhancement of sprouting and maturation of peripheral axons.