MiR-124 Reduced Neuroinflammation after Traumatic Brain Injury by Inhibiting TRAF6
- 1 Department of Neurosurgery, The General Hospital of Western Theater Command, Chengdu, China.
- 2 Department of Neurosurgery, Xijing Hospital, Air Force Medical University (Fourth Military Medical University), Xi’an, China.
- 3 Department of Neurosurgery, NO. 921 Hospital of PLA Joint Support Force (Second Affiliated Hospital of Hunan Normal University), Changsha, China.
- 4 Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, China.
- PMID: 36858024
- 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.
Keywords: MiR-124; Microglia; Neuroinflammation; TLR4; TRAF6; Traumatic brain injury.