PERIPHERAL NERVE-STIMULATED MACROPHAGES SIMULATE A PERIPHERAL NERVE-LIKE REGENERATIVE RESPONSE IN RAT TRANSECTED OPTIC-NERVE

We have previously demonstrated that the failure of the mammalian cent ral nervous system (CNS) to regenerate following axonal injury is rela ted to its immunosuppressive nature, which restricts the ability of bo th recruited blood-borne monocytes and CNS-resident microglia to suppo rt a process of repair. In this study we show that transected optic ne rve transplanted with macrophages stimulated by spontaneously regenera ting nerve tissue, e.g., segments of peripheral nerve (sciatic nerve), exhibit axonal regrowth at least as far as the optic chiasma. Axonal regrowth was confirmed by double retrograde labeling of the injured op tic axons, visualized in their cell bodies. Transplanted macrophages e xposed to segments of CNS (optic) nerve were significantly less effect ive in inducing regrowth. Immunocytochemical analysis showed that the induced regrowth was correlated with a wide distribution of macrophage s within the transplanted-transected nerves. It was also correlated wi th an enhanced clearance of myelin, known to be inhibitory for regrowt h and poorly eliminated after injury in the CNS. These results suggest that healing of the injured mammalian CNS, like healing of any other injured tissue, requires the partnership of the immune system, which i s normally restricted, but that the restriction can be circumvented by transplantation of peripheral nerve-stimulated macrophages. (C) 1998 Wiley-Liss, Inc.