MiR-124 Reduced Neuroinflammation after Traumatic Brain Injury by Inhibiting TRAF6

• Published in: Neuroimmunomodulation 2023-01, Vol.30 (1), p.55-68
• Main Authors: Yang, Yongxiang, Ye, Yuqin, Fan, Kexia, Luo, Jianing, Yang, Yongjian, Ma, Yuan
• Format: Article
• Language: English
• Subjects: Animals; Brain Injuries, Traumatic - complications; Brain Injuries, Traumatic - metabolism; Microglia - metabolism; MicroRNAs - metabolism; Neuroinflammatory Diseases; NF-kappa B - metabolism; Research Article; TNF Receptor-Associated Factor 6 - metabolism; Toll-Like Receptor 4
• ISSN: 1021-7401; 1423-0216; 1423-0216
• DOI: 10.1159/000528502

Introduction: Neuroinflammation contributes to secondary injury after traumatic brain injury (TBI), which has been mainly mediated by the microglia. MiR-124 was reported to play an important role in the polarization of microglia by targeting TLR4 signaling pathway. However, the role and mechanism of miR-124 in neuroinflammation mediated by microglia after TBI is unclear. To clarify this, we performed this research. Methods: The expression of miR-124 was first measured by RT-PCR in the injured brain at 1/3/7 days post-TBI. Then, miR-124 mimics or inhibitors administration was used to interfere the expression of miR-124 at 24 h post-TBI. Subsequently, the microglia polarization markers were detected by RT-PCR, the expression of inflammatory cytokines was detected by ELISA, the expression of TLR4/MyD88/IRAK1/TRAF6/NF-κB was measured by WB, and the neurological deficit was evaluated by NSS and MWM test. At last, in vitro experiments were performed to explore the exact target molecule of miR-124 on TLR4 signaling pathway. Results: Animal research indicated that the expression of miR-124 was downregulated after TBI. Upregulation of miR-124 promoted the M2 polarization of microglia and inhibited the activity of TLR4 pathway, as well as reduced neuroinflammation and neurological deficit after TBI. In vitro experiments indicated that miR-124 promoted the M2 polarization of microglia and reduced neuroinflammation by inhibiting TRAF6. Conclusion: This study demonstrated that upregulation of miR-124 promoted the M2 polarization of microglia and reduced neuroinflammation after TBI by inhibiting TRAF6.