Creatine promotes the repair of peripheral nerve injury by affecting macrophage polarization

The present study aimed to explore whether creatine promotes the repair of peripheral nerve injury and its possible mechanism. In vitro: RAW264.7 cells were used to investigate the role of proteins related to the JAK2/STAT1 pathway in the polarization of macrophages treated with creatine. In vivo: A sciatic nerve crush model was used. After the injury, IL-4 or creatine was injected. The recovery of motor function was assessed by the rotarod test and sciatic function index at 2, 6, 10, and 16 days after injury. At 16 days after injury, the ultrastructure of the nerve tissue was observed under a transmission electron microscope. Immunostaining were performed at 4 and 16 days to investigate the expression levels of macrophage-related markers as well as the distribution of macrophages after injury. Compared with the IFN-γ group, the group pretreated with creatine showed a significant decrease in p-JAK2 and p-STAT1 in vitro. The motor function of mice in the creatine group (CR₁) and creatine 4 days group (CR₂) was significantly improved compared to the control group (CON). The improvement in the CR₂ group was more significant. Immunostaining showed that infiltrating macrophages mainly comprised M1 macrophages in the CON group and M2 macrophages in the CR group. Our study shows that creatine promotes the repair of peripheral nerve injury by affecting macrophage polarization, possibly through decreasing M1 polarization by inhibiting the JAK2/STAT1 pathway.