Department of Neurosurgery, The General Hospital of Western Theater Command, Chengdu, China.
Department of Neurosurgery, Xijing Hospital, Air Force Medical University (Fourth Military Medical University), Xi'an, China.
Neuroimmunomodulation. 2023;30(1):55-68. doi: 10.1159/000528502. Epub 2023 Mar 1.
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.
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.
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.
This study demonstrated that upregulation of miR-124 promoted the M2 polarization of microglia and reduced neuroinflammation after TBI by inhibiting TRAF6.
神经炎症参与创伤性脑损伤（TBI）后的继发性损伤，主要由小胶质细胞介导。miR-124 被报道通过靶向 TLR4 信号通路在小胶质细胞极化中发挥重要作用。然而，miR-124 在 TBI 后小胶质细胞介导的神经炎症中的作用和机制尚不清楚。为了阐明这一点，我们进行了这项研究。
首先通过 RT-PCR 测量 TBI 后 1/3/7 天损伤大脑中 miR-124 的表达。然后，在 TBI 后 24 小时用 miR-124 模拟物或抑制剂处理以干扰 miR-124 的表达。随后，通过 RT-PCR 检测小胶质细胞极化标志物，通过 ELISA 检测炎症细胞因子的表达，通过 WB 测量 TLR4/MyD88/IRAK1/TRAF6/NF-κB 的表达，并通过 NSS 和 MWM 测试评估神经功能缺损。最后，进行体外实验以探索 miR-124 在 TLR4 信号通路的确切靶分子。
动物研究表明，TBI 后 miR-124 的表达下调。miR-124 的上调促进了小胶质细胞的 M2 极化，并抑制了 TLR4 通路的活性，从而减轻了 TBI 后的神经炎症和神经功能缺损。体外实验表明，miR-124 通过抑制 TRAF6 促进小胶质细胞的 M2 极化并减轻神经炎症。
这项研究表明，上调 miR-124 通过抑制 TRAF6 促进 TBI 后小胶质细胞的 M2 极化并减轻神经炎症。
