Prevention of macrophage invasion impairs regeneration in nerve grafts

The importance of cell invasion for regeneration in nerve segments was investigated in rats. The regeneration distance of axons in predegenerated nerve segments was compared to the outgrowth in nerve segments where cell invasion had been prevented. A 10 mm long nerve segment, which was predegenerated (preserved or impaired blood circulation) or kept in a Millipore chamber (pore size 0.22 microns), was sutured as a nerve graft at the contralateral side three days or two weeks after the initial procedure. At two weeks immunocytochemical staining and routine histologic analysis revealed pronounced myelin breakdown and presence of ED1 and ED2 positive macrophages in the predegenerated nerve segment. Nerve segments, which were kept in the Millipore chamber, showed no invasion of macrophages and the myelin sheaths were preserved. The regeneration distances of axons in the nerve segments, evaluated with the pinch reflex test, were significantly longer in the predegenerated nerve segments compared to the nerve segments kept in Millipore chambers. Nerve grafts, which were taken from predegenerated nerves with intact blood circulation, showed the longest regeneration distances. It is suggested that the regeneration process can be impaired in nerve segments where cell and macrophage invasion as well as myelin breakdown are prevented and that preservation of the blood circulation during the degeneration process is important.