DIFFERENTIAL MACROPHAGE RESPONSES IN THE PERIPHERAL AND CENTRAL-NERVOUS-SYSTEM DURING WALLERIAN DEGENERATION OF AXONS

We characterized quantitatively the macrophage response following axon al injury in both the peripheral (PNS) and central nervous system (CNS ) of adult mammals. A monoclonal antibody (ED-I) which stains monocyte s, macrophages, and activated microglia was employed. In one model, Wa llerian degeneration of-the sciatic nerve was studied. An increase in the number of macrophages was seen as early as 1 day following nerve t ransection. Macrophage number increased synchronously along the length of degenerating nerve over a 21-day period. In a second model, transe ction of a spinal dorsal sensory root allowed us to compare and contra st the macrophage response along the PNS and CNS portions of a single axonal pathway. An increased number of macrophages restricted to the P NS portion of this pathway was seen by 3 days and continued to increas e over a 14-day period. Myelin breakdown occurred in association with an increase in the number of macrophages by 3 days in the PNS but not the CNS portion of the degenerating dorsal root axon pathway. Low-affi nity nerve growth factor receptor immunohistochemical staining increas ed by Day 1 in the PNS but not the CNS portion of this pathway, occurr ing prior to the invasion of macrophages. In both models, the morpholo gy of infiltrating macrophages changed over time from small slender ra mified cells to large elongated multivacuolated cells. In conclusion, our results demonstrate that the macrophage response during Wallerian degeneration of axons in adult mammals is much more rapid and robust i n the PNS, where axonal regeneration occurs, than in the CNS, where ax onal regeneration is far more limited. (C) 1995 Academic Press, Inc.