LONG-DISTANCE AXONAL REGENERATION IN THE TRANSECTED ADULT-RAT SPINAL-CORD IS PROMOTED BY OLFACTORY ENSHEATHING GLIA TRANSPLANTS

The lack of axonal regeneration in the injured adult mammalian spinal cord leads to permanent functional impairment. To induce axonal regene ration in the transected adult rat spinal cord, we have used the axona l growth-promoting properties of adult olfactory bulb ensheathing glia (EG). Schwann cell (SC) filled guidance channels were grafted to brid ge both cord stumps, and suspensions of pure (98%) Hoechst-labeled EG were stereotaxically injected into the midline of both stumps, 1 mm fr om the edges of the channel. In EG-transplanted animals, numerous neur ofilament-, GAP-43-, anti-calcitonin gene-related peptide (CGRP)-, and serotonin-immunoreactive fibers traversed the glial scars formed at b oth cord-graft interfaces. Supraspinal serotonergic axons crossed the transection gap through connective tissue bridges formed on the exteri or of the channels, avoiding the channel interior. Strikingly, after c rossing the distal glial scar, these fibers elongated in white and per iaqueductal gray matter, reaching the farthest distance analyzed (1.5 cm). Tracer-labeled axons present in SC grafts were found to extend ac ross the distal interface and up to 800 mu m beyond in the distal cord . Long-distance regeneration (at least 2.5 cm) of injured ascending pr opriospinal axons was observed in the rostral spinal cord. Transplante d EG migrated longitudinally and laterally from the injection sites, r eaching the farthest distance analyzed (1.5 cm). They moved through wh ite matter tracts, gray matter, and glial scars, overcoming the inhibi tory nature of the CNS environment, and invaded SC and connective tiss ue bridges and the dorsal and ventral roots adjacent to the transectio n site. Transplanted EG and regenerating axons were found in the same locations. Because EG seem to provide injured spinal axons with approp riate factors for long-distance elongation, these cells offer new poss ibilities for treatment of CNS conditions that require axonal regenera tion.