Modulation of the macrophage/microglial response during axonal degeneration in the mammalian PNS and CNS

Following axonal injury, macrophages are intensely recruited and activated in the mammalian peripheral (PNS) but not central (CNS) nervous system. This differential response is clearly demonstrated by degenerating dorsal roots where a robust macrophage response is seen in the PNS but not the CNS portion of the injured nerves. Regenerating dorsal root axons follow a similar pattern, growing through the PNS but not the CNS portion of this pathway. The aim of this study was to enhance the macrophage/microglial response within the CNS following dorsal root injury. Uninjured Lewis rats (Group I: n=6) received 4 daily intraperitoneal (IP) injections of I mg lipopolysaccharide (LPS), a bacterial endotoxin that activates macrophages. Additional rats underwent transection of lumbar dorsal roots followed by 4 daily IP injections of either saline (Group II: n=6) or LPS (Group III: n=6). Seven days after surgery, the animals were sacrificed and their lumbar spinal cords with attached dorsal roots were removed and stained. ED-1, a marker for rat monocytes, macrophages, and activated microglia was employed. Group I rats demonstrated increased ED-1 staining of microglia throughout the spinal cord. Group II rats demonstrated markedly increased ED-1 staining confined to the PNS portion of degenerating dorsal roots. Group III rats demonstrated increased ED-1 staining of macrophage/microglia along both PNS and CNS portions of degenerating dorsal roots. In all groups, myelin breakdown within the PNS and CNS occurred only where activated ED-1 staining macrophage/microglia were present. In summary, LPS induces a macrophage/microglia response in the CNS similar to that seen in the PNS following dorsal root trauma. Experiments to determine if enhancement of the CNS macrophage/microglia response allows the regeneration of dorsal root axons into the spinal cord are in progress.