Cerebral ischemia induces the expression of several
growth factors and
cytokines, which protect neurons against ischemic insults. Recent studies showed that
granulocyte colony-stimulating factor (
G-CSF) has a
neuroprotective effect through the signaling pathway for the antiapoptotic cascade. The current study was designed to assess the neuroprotective mechanisms of
G-CSF in
ischemia/reperfusion injury using bone marrow chimera mice known to express
enhanced green fluorescent protein (EGFP). Mice were subjected to
ischemia/reperfusion and divided into two groups: those treated with
G-CSF (
G-CSF group) and vehicle (control group) (n = 35 in each group). Immunohistochemistry and immunoblotting for antiapoptotic
protein,
nitrotyrosine, and inducible
nitrate oxide synthase (iNOS) were performed.
G-CSF significantly reduced stroke volume (34%, P < 0.006).
G-CSF upregulated Stat3, pStat3, and Bcl-2 (P < 0.05), and suppressed iNOS and
nitrotyrosine expression. In EGFP chimera mice,
G-CSF decreased the migration of Iba-1/EGFP-positive bone marrow-derived monocytes/macrophages and increased intrinsic microglia/macrophages at ischemic penumbra (P < 0.05), suggesting that bone marrow-derived monocytes/macrophages are not involved in
G-CSF-induced reduction of ischemic injury size. Our study indicated that
G-CSF exerts a
neuroprotective effect through the direct activation of antiapoptotic pathway, and suggested that
G-CSF is important for expansion of the therapeutic time window in patients with
cerebral ischemia.