Abstract
Granulocyte colony-stimulating factor (G-CSF) and its related mechanisms were investigated to assess the potential for this factor to exert neuroprotective effects against spinal cord injury in mice. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) was injected into mice spinal cord hemisection models. Locomotor activity was assessed by using the Basso-Bettie-Bresnahan scale. Neurons isolated from spinal cords were cultured in vitro and used in a neuronal mechanical injury model. Three treatment groups were compared with this model, 1) G-CSF, 2) G-CSF + NSC348884 (a nucleophosmin 1-specific inhibitor), and 3) NSC348884. Immunofluorescence staining and Western blotting were performed to analyze the expression of G-CSF and nucleophosmin 1 (Npm1). TUNEL staining was performed to analyze apoptosis after G-CSF treatment. We found that the G-CSF receptor (G-CSFR) and Npm1 were expressed in neurons and that Npm1 expression was induced after G-CSF treatment. G-CSF inhibited neuronal apoptosis. NSC348884 induced p53-dependent cell apoptosis and partially blocked the neuroprotective activity of G-CSF on neurons in vitro. G-CSF promoted locomotor recovery and demonstrated neuroprotective effects in an acute spinal cord injury model. The mechanism of G-CSF's neuroprotection may be related in part to attenuating neuronal apoptosis by NPM1.