Macrophage colony-stimulating factor is expressed in neuron and microglia after focal brain injury

In a previous study, we have demonstrated that damaged neurons within a bou ndary area around necrosis fall into delayed neuronal death owing to the cy totoxic effect of microglial nitric oxide (NO), and these neurons are final ly eliminated by activated microglia. In this process, microglia are activa ted to release NO, increase in number, and accumulate toward the damaged ar ea. In this study, we investigated the expression of macrophage colony-stim ulating factor (M-CSF, also called colony stimulating factor-1; CSF-1) and other cytokines, which are reported to relate to activation, proliferation, or migration of microglia. The mRNA of M-CSF arose biphasically from 30 mi n to 1 hr and from 6 to 72 hr after the injury, as demonstrated by semiquan titative RT-PCR. However, another cytokine of granulocyte-macrophage CSF (G M-CSF) or interleukin-3 (IL-3), which causes proliferation of microglia in vitro, was nor detected. From immunohistochemical studies, positive stainin g of M-CSF was observed mainly in neuron-specific enolase (NSE)-positive ce lls from 1 to 12 hr after the injury, and after that M-CSF became positive in Griffonia simplicifolia isolectin-B4 (GSA-I-B4)-positive cells from 24 t o 72 hr in the boundary area around necrosis. These results suggest that ne urons around the damaged area express M-CSF in the early phase after injury , which may initially activate microglia, and these activated microglia als o express M-CSF later, causing further proliferation or migration of microg lia themselves to eliminate damaged neurons or necrotic brain tissue. J. Ne urosci. Res. 65:38-44, 2001. (C) 2001 Wiley-Liss, Inc.