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 hea d of the fibula. At various intervals from 1 day to 2, 3, 5, 15, and 25 day s, a test lesion was made by axotomy 15 mm proximal to the conditioning les ion 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 vis ualized on the him with silver nitrate impregnation. Schwann cells were vis ualized 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 cont ralateral limb and 2 days later the film was harvested for histological exa mination. Conditioned by a prior axotomy more than 3 days earlier, regenera ting axons sprouted within less than 1 h after the test lesion was establis hed and grew naked at five times higher rate: The growth rate was similar t o that observed during regeneration in the presence of migratory Schwann ce lls (ordinary type). After a short interval, the axons, which had been ensh eathed by migratory Schwann cells (reactive type), continued growing at a s ignificantly (P < 0.01) higher rate. The reactive type of cells had fewer n umbers of branches and higher activity in promoting axonal outgrowth than t he ordinary type. Thus, both ordinary and reactive types of cells played ke y roles in initiating and maintaining a conditioning effect, respectively. (C) 1999 Academic Press.