Modulation of macrophage and microglial responses to axonal injury in the peripheral and central nervous systems

OBJECTIVE: After axonal injury, macrophages rapidly infiltrate and become a ctivated in the mammalian peripheral nervous system (PNS) but not the centr al nervous system (CNS). We used the dorsal root pathway to study factors t hat modulate the response of macrophages to degenerating axons in both the PNS and the CNS. METHODS: Lewis rats underwent transection of dorsal roots (Group I), stab w ithin the spinal cord (Group II), crush at the dorsal root entry zone (Crou p III), transection of dorsal roots combined with a CNS lesion (Group IV), or systemic administration of a known activator of macrophages, lipopolysac charide, alone (Group V) or combined with transection of dorsal roots (Grou p VI). ED-1 antibody stained for macrophages and activated microglia at 7, 14, and 42 days postinjury. RESULTS: At early time points, Group I demonstrated ED-1 cells in the PNS b ut not the CNS portion of the degenerating dorsal roots, Group II revealed ED-1 cells near the stab lesion. Group III demonstrated ED-1 cells adjacent to the dorsal root entry zone crush site. Group IV revealed ED-1 cells alo ng both the PNS and the CNS portions of the degenerating dorsal roots when the CNS lesion was placed near the transected roots. Group V demonstrated f ew ED-1 cells in the PNS and the CNS, whereas Group V1 revealed a marked ED -1 cellular response along both the PNS and the CNS portions of the transec ted dorsal roots. CONCLUSION: Local CNS trauma and systemic administration of lipopolysacchar ide can "prime" macrophages/microglia, resulting in an enhanced response to degenerating axons in the CNS. Such priming might prove useful in promotin g axonal regeneration.