Inhibition of HMGB1 mediates neuroprotection of traumatic brain injury by modulating the microglia/macrophage polarization

Highlights: • Treatment with GL could improve the neurological function recovery and reduce the lesion volume after TBI. • Administration of GL could inhibit the release and expression of HMGB1. • Treatment with GL could inhibit M1 phenotype while promoted M2 phenotype activation of microglia/macrophages after TBI. Microglia/Macrophages have a double-edged role in secondary brain damage after traumatic brain injury (TBI) depending on polarization toward proinflammatory M1 or anti-inflammatory M2 phenotypes. Recently, high-mobility group box 1 (HMGB1) was found to influence the polarization of macrophages. In this study, glycyrrhizin (GL), an inhibitor of HMGB1, was used to investigate whether the inhibition of HMGB1 could modulate microglia/macrophage polarization after TBI. The results showed that treatment with GL improved the neurological function recovery, reduced the lesion volume, and inhibited the release and expression of HMGB1 after TBI. In addition, the administration of GL suppressed M1 phenotype activation and promoted M2 phenotype activation of microglia/macrophages. In conclusion, the results suggested that GL attenuated TBI by inhibiting M1 phenotype while inducing M2 phenotype activation of microglia/macrophages, at least partly through inhibiting HMGB1. Also, targeting HMGB1 to modulate the microglia/macrophage polarization should be one potential therapeutic approach for TBI.