The protective effects of nesfatin‐1 in neurological dysfunction after spinal cord injury by inhibiting neuroinflammation

AIMS: Spinal cord injury (SCI) is one of the most severe neurological diseases. However, there is still no effective treatment for it. Nesfatin, a precursor neuropeptide derived from nucleobindin 2 (NUCB2), has displayed a wide range of protective effects in different types of cells and tissue. However, the effects of nesfatin‐1 in SCI have not been reported before. MATERIALS AND METHODS: A SCI model was established. The behavior of mice was assessed using the Basso, Beattie, and Bresnahan (BBB) assessment. RESULTS: Here, we report that the administration of nesfatin‐1 improved neurological recovery in SCI mice by increasing BBB scores, reducing lesion area volume and spinal cord water content. Also, nesfatin‐1 ameliorated oxidative stress by reducing reactive oxygen species (ROS) levels and increasing superoxide dismutase (SOD) activity. We also found that nesfatin‐1 prevented neuronal apoptosis in SCI mice by reducing caspase 3 activity and the expression of Bax, as well as increasing B‐cell lymphoma‐2 (Bcl‐2). Additionally, nesfatin‐1 reduced the levels of interleukin 6 (IL‐6), interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α). Nesfatin‐1 also promoted microglia towards M2 polarization by increasing the marker CD206 but reducing CD16. Importantly, nesfatin‐1 enhanced the phosphorylation of signal transducer and activator of transcription 1 (STAT1) but reduced the expression levels of toll‐like receptor 4 (TLR4) and phosphorylated nuclear factor kappa‐B p65 (p‐NF‐κB p65). CONCLUSION: Our findings imply that nesfatin‐1 exerts neuroprotective actions in SCI by promoting the activation of M2 microglia, and its underlying mechanisms might be related to the activation of STAT1 and inhibition of the TLR4/NF‐κB signaling pathway.