REGENERATION OF CUT ADULT AXONS FAILS EVEN IN THE PRESENCE OF CONTINUOUS ALIGNED GLIAL PATHWAYS

The present study tests whether lesions small enough to allow the rapi d reestablishment of a normally aligned tract glial framework would pr ovide a permissive environment for the regeneration of cut adult CNS a xons. We made penetrating microlesions which cut a narrow beam of axon s in the adult rat cingulum, but caused minimal damage to the tract gl ial framework and no cavitation. The proximal tips of cut axons were i dentified by enhanced immunoreactivity for low affinity neurotrophin r eceptor, p75. From 1 day they be came expanded into large growth-cone- like structures. At later times some axons turned back and extended in the reverse direction. Up to 14 days (after which time p75 could no l onger be used as a marker), no axons advanced beyond the line of the l esion. From 1 to 2 days, OX42 immunostaining and electron microscopy s howed that the lesion site was densely infiltrated by macrophages, whi ch disappeared by 3 to 4 days. This was followed by a local hypertroph y of the OX42 immunoreactive resident tract microglial cells and an in crease in both GFAP and vimentin immunoreactivity of the tract astrocy tes. These responses were greatly reduced by 8 days, when the longitud inal alignment of glial processes across the lesion site was similar t o that of an undamaged tract. The large growth-cone-like structures fo rmed at the ends of the cut axons resemble those of developing axons e xposed to chemorepulsive factors. This suggests that cellular elements in adult tract lesions may also exert chemorepulsive influences block ing regeneration of axons even in an apparently ''open'' tract framewo rk. (C) 1996 Academic Press, Inc.