Traumatic brain injury (TBI) can lead to different neurological and psychiatric disorders. Circular RNAs (circRNAs) are highly expressed in the nervous system and enriched in synapses; yet, the underlying role and mechanisms of circRNAs in neurological impairment and dysfunction are still not fully understood. In this study, we investigated the expression of circRNAs and their relation with neurological dysfunction after TBI. RNA-Seq was used to detect differentially expressed circRNAs in injured brain tissue, revealing that circIgfbp2 was significantly increased. Up-regulated hsa_circ_0058195, which was highly homologous to circIgfbp2, was further confirmed in the cerebral cortex specimens and serum samples of patients after TBI. Moreover, correlation analysis showed a positive correlation between hsa_circ_0058195 levels and the Self-Rating Anxiety Scale scores in these subjects. Furthermore, knockdown of circIgfbp2 in mice relieved anxiety-like behaviors and sleep disturbances induced by TBI. Knockdown of circIgfbp2 in H₂O₂ treated HT22 cells alleviated mitochondrial dysfunction, while its overexpression reversed the process. Mechanistically, we discovered that circIgfbp2 targets miR-370-3p to regulate BACH1, and down-regulating BACH1 alleviated mitochondrial dysfunction and oxidative stress-induced synapse dysfunction. In conclusion, inhibition of circIgfbp2 alleviated mitochondrial dysfunction and oxidative stress-induced synapse dysfunction after TBI through the miR-370-3p/BACH1/HO-1 axis. Thus, circIgfbp2 might be a novel therapeutic target for anxiety and sleep disorders after TBI.

创伤性脑损伤 (TBI) 可导致不同的神经和精神疾病。环状 RNA (circRNA) 在神经系统中高表达，并在突触中富集；然而，circRNA 在神经损伤和功能障碍中的潜在作用和机制仍未完全了解。在这项研究中，我们研究了 circRNA 的表达及其与 TBI 后神经功能障碍的关系。RNA-Seq 用于检测损伤脑组织中差异表达的 circRNA，揭示 circIgfbp2 显着增加。在TBI后患者的大脑皮层标本和血清样本中进一步证实了与circIgfbp2高度同源的hsa_circ_0058195上调。而且，相关分析显示，这些受试者的 hsa_circ_0058195 水平与焦虑自评量表得分呈正相关。此外，在小鼠中敲低 circIgfbp2 可缓解 TBI 引起的焦虑样行为和睡眠障碍。H 中 circIgfbp2 的敲除₂ O ₂处理的HT22细胞减轻了线粒体功能障碍，而其过表达则逆转了这一过程。从机制上讲，我们发现 circIgfbp2 靶向 miR-370-3p 来调节 BACH1，下调 BACH1 可减轻线粒体功能障碍和氧化应激诱导的突触功能障碍。总之，抑制 circIgfbp2 通过 miR-370-3p/BACH1/HO-1 轴减轻 TBI 后线粒体功能障碍和氧化应激诱导的突触功能障碍。因此，circIgfbp2 可能是 TBI 后焦虑和睡眠障碍的新治疗靶点。