Miconazole alleviates peripheral nerve crush injury by mediating a macrophage phenotype change through the NF‐κB pathway

Background Peripheral nerve injury (PNI) causes motor and sensory defects, has strong impact on life quality and still has no effective therapy. Miconazole is one of the most widely used antifungal drugs; the aims of the study were to investigate the effects of miconazole during sciatic nerve regeneration in a mouse model of sciatic nerve crush injury. Methods We established peripheral nerve crush model and investigated the effects of miconazole by multiple aspects. We further studied the potential mechanism of action of miconazole by Western blotting, fluorescence immunohistochemistry, and PCR analysis. Results Miconazole improves the symptoms of crushed nerve by improving inflammatory cell infiltration and demyelinating myelin of sciatic nerve. Affected by miconazole, the proportion of inflammatory M1 macrophages in the distal part of the sciatic nerve was reduced, and the proportion of anti‐inflammatory M2 macrophages was increased. Finally, the neuroprotective properties of miconazole may be regulated by the nuclear factor (NF)‐κB pathway. Conclusions Our data suggest that miconazole can effectively alleviate PNI, and the mechanism involves mediating a phenotype change of M1/ M2 macrophages. Thus, miconazole may represent a potential therapeutic intervention for nerve crush injury. Miconazole protects against sciatic nerve crush injury. Miconazole promotes M2 macrophage polarization in vivo and in vitro. Miconazole‐related protection is mediated by the NF‐κB pathway.