| Abstract: | The central nervous systems of mammals and fish differ significantly in their ability to regenerate. Central nervous system axons in the fish readily regenerate after injury, while in mammals they begin to elongate but their growth is aborted a the site of injury, an area previously shown to contain no glial cells. In the present study we compared the ability of glial cells to migrate and thus to repopulate the injured area in fish and rats, and used light and electron microscopy in an attempt to correlate such migration with the ability of axons to traverse this area. One week after the optic nerve was crushed, both axonal and glial responses to injury were similar in fish and rat. In both species glial cells were absent in the injured area (indicated by the disappearance of glial fibrillary acidic protein and vimentin immunoreactive cells from the site of injury in rat and fish, respectively), while at the same time axonal growth, indicated by expression of the growth-associated protein GAP-43, was restricted to the proximal part of the nerve. In fish, 2 weeks after the crush, GAP-43 staining (i.e., growing axons) was seen at the site of injury, in association with migrating vimentin-positive glial cells. One week later the site of injury in the fish optic nerve was repopulated by vimentin-positive glial cells, and GAP-43-positive axons had already traversed the site of injury and reached the distal part of the nerve. In contrast, the site of injury in the rat remained devoid of glial fibrillary acidic protein immunoreactive cells, and the expression of GAP-43 by growing axons was still restricted to the proximal part of the nerve. Double-labeling experiments and transmission electron microscopy performed 2 weeks after crush injury of the fish optic nerve revealed that the frontier of axonal growth (i.e., the leading growth cones) appeared to be 200–300 μm ahead of the nearest vimentin-positive glial cells. The leading growth cones were associated with other cells, presumably glial precursors, that seemed to have a high migratory potential. We suggest that the ability of fish glial precursor cells to migrate into the injured area may contribute to the potential of growing axons to traverse this area. The failure of glia and glial precursor cells to migrate into the injured area in the rat may partially account for the failure of rat axons to enter and traverse the injured area. |
