Abstract:

Objective   To explore the alteration of microglial protection/injury function caused by granulocyte-colony stimulating factor (G-CSF) in the acute spinal cord injury mice model. Methods   Hemi-section injuries were produced by cutting one-half of the right lateral portion of the spinal cord. After surgery the mice were given an intraperitoneal injection of rhG-CSF, which continued 3 days. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to analyze behavior and then the spinal cord was taken out for histological analysis by immunofluorescence to observe the accumulation of microglia in vivo. Microglial cell line BV-2 cells were pretreated with normal and injury spinal cord supernatant for 24h, followed by a 12h administration of G-CSF(100ng/mL), then harvested the cells. RT-PCR and Western blot were employed to evaluate the changes of microglial cytokines and pathways in vitro. Results   In the G-CSF treatment group, improvement in hind-limb motor function and accumulation of microglial cell were significantly greater than in the sham-treatment (vehicle) group. As the results in vitro showed, in the G-CSF treatment group, the activity of NF-κB p65 was inhibited and the secretion of microglial cytokines was changed. In addition, expression of pro-inflammation cytokine IL-1β decreased and anti-inflammation cytokine TGFβ increased. Conclusions   In this study, the administration of G-CSF in acute spinal cord injury not only improved motor function, but also regulated the distribution and function of microglia as well as to induce the microglia altering to neural protection.

Key words: pinal cord injuries; Granulocyte colony-stimulating factor; Microglia; Neuroprotective agents