High-dosage granulocyte colony stimulating factor treatment alters monocyte trafficking to the brain after experimental stroke

摘要: Abstract Ischemic stroke elicits a prompt inflammatory response that is characterized by well-timed recruitment of peripheral immune cells to the brain. Among these, monocytes play particularly important, but multifaceted role and have been increasingly recognized affect outcome. Granulocyte colony stimulating factor (GCSF) known for its immunosuppressive actions on mononuclear cells, previous studies in field were mainly confined neuroprotective actions. Herein, we investigated whether GCSF affects post-stroke inflammation mouse model focal brain ischemia modulating monocyte responses. Treatment with was controlled vehicle injection, sham surgery naive animals. Despite significant monocytosis, high-dosage reduced number brain-infiltrating monocytes/macrophages four days after stroke. Lower numbers phagocytes associated smaller cerebral edema improved motor outcome treatment over 72 h, not 24 h diminished integrin expression circulating Ly6C+ monocytes. In vitro experiments further revealed strongly promotes interleukin (IL)-10 secretion activated cells. Blockade IL-10 receptor partly reversed GCSF-induced downregulation surface expression. Overall, our results suggest mitigates infiltration stroke, likely attenuating integrin-mediated adhesion endothelium an IL-10-dependent manner. amounts translate less severe functional impairment thus support harmful acute stage