AIF-1 expression defines a proliferating and alert microglial/macrophage phenotype following spinal cord injury in rats

Microglial cells are among the first and dominant cell types to respond to CNS injury. Following calcium influx, microglial activation leads to a vari ety of cellular responses, such as proliferation and release of cytotoxic a nd neurotrophic mediators. Allograft inflammatory factor-1, AIF-1 is a high ly conserved EF-handed, putative calcium binding peptide, associated with m icro.-lia activation in the brain. Here, we have analyzed the expression of AIF-1 following spinal cord injury at the lesion site and at remote brain regions. Following spinal cord injury, AIF-1(+) cells accumulated in parenc hymal pan-necrotic areas and perivascular Virchow-Robin spaces. Subsequent to culmination at day 3-a situation characterized by infiltrating blood bor ne macrophages and microglia activation-AIF-1(+) cell numbers decreased unt il day 7. In remote areas of Wallerian degeneration and delayed neuronal de ath, a more discrete and delayed activation pattern of AIF-1(+) microglia/m acrophages reaching maximum levels at day 14 was observed. There was a cons iderable match between AIF-1(+) cells and PCNA (proliferating cell nuclear antigen) or Ki-67(+) labeled cells. AIF-1 expression preceded the expressio n of ED1, thus indicating a pre-phagocytic role. It appears that AIF-1(+) m icroglia/macrophages are among the earliest cells to respond to spinal cord injury. Our results suggest a role of AIF-1 in the initiation of the early microglial response leading to activation and proliferation essential for the acute response to CNS injury. AIF-1 might modulate microgliosis influen cing the efficacy of tissue debris removal, myelin degradation, recruitment of oligodendrocytes and re-organisation of the CNS architecture. (C) 2001 Elsevier Science BN. All rights reserved.