Therapeutic and Mechanistic Effects of Granulocyte Colony Stimulating Factor and Neurotrophin Receptor on Cerebral Ischemia-Reperfusion Injury: An Experimental Pilot Study.

Objective: To study the therapeutic effect and protective mechanism of granulocyte colony stimulating factor (G-CSF) and neurotrophin receptor (NTR) on cerebral ischemia-reperfusion injury.

Methods: Rat models of permanent focal middle cerebral artery occlusion (MCAO) were constructed by using a modified suture method, and the rats were assigned into three groups such as treatment group (the rats were injected with mixed G-CSF and NTR once), sham operation group and PBS control group. The volume of the cerebral infarction was detected using Triphenyltetrazolium Chloride (TTC) staining method; the motor function in rats was evaluated; and qRT-PCR detection, double immunofluorescence histochemistry and immunohistochemistry were performed to observe various effects.

Results: After G-CSF and NTR treatment, the infarct volume induced by MCAO in the treatment group was significantly lower than that in the PBS control group (P<0.05). The motor function in the treatment group was significantly improved on day 7 and day 14 compared to the PBS control group (P<0.05). The levels of MCP-1, TNF-α, TGF-β and IL-10 mRNA in the treatment group decreased by 22% compared with PBS control group, and the difference was statistically significant (P<0.05). The Bcl-2 protein level in the treatment group was greater than that in the PBS control group, while the Bax level in the treatment group was lower than in the control group; and both the differences were statistically significant (P<0.05). The number of BrdU + cells in the treatment group was significantly greater than that in the PBS control group (P<0.05).

Conclusion: G-CSF can promote the regeneration of neurons, promote the formation of new blood vessels, promote the reconstruction of neural network in rat MCAO models through anti apoptosis, anti-inflammation and mobilization of bone marrow hematopoietic cells to exert its powerful protective effect on neurons, and contribute to the repair of neural function and improvement of prognosis.