Exogenous NT-3 Promotes Phenotype Switch of Resident Macrophages and Improves Sciatic Nerve Injury through AMPK/NF-κB Signaling Pathway

Abstract

Neurotrophin-3 (NT-3) is an important family of neurotrophic factors with extensive neurotrophic activity, which can maintain the survival and regeneration of nerve cells. However, the mechanism of NT-3 on macrophage phenotype transformation after sciatic nerve injury is not clear. In this study, we constructed a scientific nerve compression injury animal model and administered different doses of NT-3 treatment through osmotic minipump. 7 days after surgery, we collected sciatic nerve tissue and observed the distribution of macrophage phenotype through iNOS and CD206 immunofluorescence. During the experiment, regular postoperative observations were conducted on rats. After the experiment, sciatic nerve tissue was collected for HE staining, myelin staining, immunofluorescence staining, and Western blot analysis. To verify the role of the AMPK/NF-κB pathway, we applied the AMPK inhibitor Compound C and the NF-κB inhibitor BAY11-7082 to repeat the above experiment. Our experimental results reveal that NT-3 promotes sciatic nerve injury repair and polarization of M2 macrophage phenotype, promotes AMPK activation, and inhibits NF-κB activation. The repair effect of high concentration NT-3 on sciatic nerve injury is significantly enhanced compared to low concentration. Compound C administration can weaken the effect of NT-3, while BAY 11-7082 can enhance the effect of NT-3. In short, NT-3 significantly improves sciatic nerve injury in rats, promotes sciatic nerve function repair, accelerates M2 macrophage phenotype polarization, and improves neuroinflammatory response. The protective effects of NT-3 mentioned above are partially related to the AMPK/NF-κB signal axis.