A role of migratory Schwann cells in a conditioning effect of peripheral nerve regeneration.

The common peroneal nerve in mice was conditioned by axotomy around the head of the fibula. At various intervals from 1 day to 2, 3, 5, 15, and 25 days, a test lesion was made by axotomy 15 mm proximal to the conditioning lesion site. The proximal stump of the transected nerve was sandwiched between two sheets of thin plastic film and remained in vivo for various intervals from 3 h to 6, 9, 12, 24, 48, 72 and 96 h. The regenerating axons were visualized on the film with silver nitrate impregnation. Schwann cells were visualized migrating onto the film using immunohistochemistry with anti-S-100. To determine the effects of migratory Schwann cells on axonal outgrowth, a film model was established on one limb. After the nerve stump was removed from the film, the treated film was transferred to a new lesion on the contralateral limb and 2 days later the film was harvested for histological examination. Conditioned by a prior axotomy more than 3 days earlier, regenerating axons sprouted within less than 1 h after the test lesion was established and grew naked at five times higher rate: The growth rate was similar to that observed during regeneration in the presence of migratory Schwann cells (ordinary type). After a short interval, the axons, which had been ensheathed by migratory Schwann cells (reactive type), continued growing at a significantly (P < 0.01) higher rate. The reactive type of cells had fewer numbers of branches and higher activity in promoting axonal outgrowth than the ordinary type. Thus, both ordinary and reactive types of cells played key roles in initiating and maintaining a conditioning effect, respectively.