Neuroprotection of granulocyte colony-stimulating factor during the acute phase of transient forebrain ischemia in gerbils

Abstract

The present study investigates the potential protective effects of granulocyte colony-stimulating factor (G-CSF) and underlying mechanisms in a gerbil model of global cerebral ischemia. We examined neuronal death, inflammatory reaction and neurogenesis in hippocampus 72h after transient forebrain ischemia and investigated functional deficits. G-CSF was administered intraperitoneally 24h before ischemia and then daily. Treatment with G-CSF at 25–50μg/kg significantly reduced neuronal loss in the hippocampus CA1 area but not at 10ug/kg. G-CSF at 50μg/kg significantly decreased the level of TNF-α, the number of Iba1 (microglia marker) positive cells and reduced locomotor activity 72h after transient forebrain ischemia. Furthermore, the number of DCX-positive cells in the hippocampal dentate gyrus increased in with G-CSF treatment. Our findings indicate that G-CSF reduces hippocampal neuronal cell death dose-dependently and attenuates sensorimotor deficits after transient forebrain ischemia. These neuroprotective effects of G-CSF may be linked to inhibition of inflammation and possibly increased neurogenesis in the hippocampus.