Traumatic brain injury (TBI) is a common neurosurgical emergency. As a macrophage in brain, microglia involves in secondary TBI injury. UCF-101, an Omi/HtrA2 inhibitor, protects against neurological disorders. This study aims to investigate the effects of UCF-101 in TBI and its mechanism. Mouse microglia cell BV2 cells were exposed to 1 µg/mL LPS to construct TBI in vitro models. Following CCK8 assay, cells were treated with LPS + UCF-101 (2, 5, 10 µM), LPS + Compound C (AMPK inhibitor, 20 µM), and LPS + UCF-101 + Compound C groups. With lactate dehydrogenase (LDH) content detection, ELISA and qRT-PCR assays were used to measure proinflammatory factors. Biomarkers of M1 (CD16/32 and iNOS) and M2 phenotypes (CD206), as well as AMPK/NF-κB pathway-related protein expression were assessed by flow cytometry, immunofluorescence, and Western blot methods. There was a decrease in M1 phenotype biomarkers and an increase in M2 phenotype biomarkers after UCF-101 treatment. UCF-101 exposure reduced TNF-α, LDH, IL-1β, IL-6, IL-8, p-NF-κB p65/NF-κB p65, and activated p-AMPK α (T172)/AMPK α (T172) expression. Importantly, further Compound C treatment counteracted these effects of UCF-101. In conclusion, UCF-101 ameliorates TBI by promoting microglia M2 polarization via AMPK/NF-κB pathways in LPS-induced BV2 cells, providing solid scientific foundation for clinical application of UCF-101 in TBI treatment.
Keywords: AMPK/NF-κB; M2 polarization; Microglia; Neuroinflammation; Traumatic brain injury; UCF-101.
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.