The source of reactive cells during central Wallerian degeneration in the goldfish: a differential irradiation protocol.

We have used a partial irradiation paradigm to examine the provenance of cells that participate in Wallerian cellular responses in the goldfish visual system. Animals which received 50 Gy whole-body gamma-irradiation showed virtually complete inhibition of the proliferative burst usually seen after optic nerve section. These animals did, however, show a robust hyperplastic response in the optic tract that we believe represents the migration of nearby microglial cells into the affected tract. When only the postcephalic body was irradiated, proliferating cells in the major hematopoietic organs of the fish, the kidney and pronephros, were substantially inhibited. Despite this, the Wallerian cellular response in the visual paths was essentially normal. Thus, there is no obligate requirement for peripheral proliferative cells to participate in central Wallerian degeneration in the fish. However, when only the head was irradiated, and the hematopoietic organs were spared, there was a proliferative response in the visual system. We believe this represents the invasion of the visual pathways by peripheral blood cells through the optic nerve lesion and blood vessels in the nerve itself. This invasion, however, is not sufficient to generate substantial hyperplasia. In summary, although we find evidence for a small contribution by exogenous cells, the major source of reactive cells during central Wallerian degeneration in the fish is the endogenous microglia. Our data underscore the importance of elucidating the mechanisms by which microglial cells are activated and the role that they play in regeneration.