Stimulation of nerve regeneration by macrophages in granulation tissue

The effects of granulation tissue exposure on regeneration of sensory axons after a test crush lesion in rat sciatic nerves were studied. Chromic catgut threads were applied subcutaneously in the back of rats. Three weeks later the surrounding granulation tissue was isolated and transposed to the sciatic or tibial nerve in the same rat. Immunocytochemical, light and electron microscopic evaluation of the isolated granulation tissue revealed numerous EDI and ED2 positive macrophages. After an additional three weeks the sciatic nerves were crushed and the axonal outgrowth lengths were measured by the pinch reflex test and by neurofilament staining 3 or 6 days later. The regeneration distances in the sciatic nerve exposed to granulation tissue were significantly longer compared with that of nerves to which only subcutaneous tissue was transposed. Thus, the nerve had become conditioned by the transposure of macrophage rich tissue. After the transposure macrophages were present close to the nerve at the time point of the test crush lesion, but no signs of degeneration or inflammation in the endoneurial space were observed. It was also found that the outgrowth lengths in the tibial nerve branch were consistently longer than in the peroneal branch of the sciatic nerve. It is concluded that granulation tissue, containing macrophages, can induce a conditioning effect in the sciatic nerve. We suggest that this effect is related to factors emanating from macrophages in the transposed tissue.