Department of Neurosurgery, General Hospital, Tianjin Neurological Institute, Tianjin Medical University, No. 154, Anshan Road, Heping District, Tianjin, 300052, P.R. China.
Department of Pharmacy, Tianjin Medical University General Hospital Airport Hospital, No. 85, East Sixth Road, Airport Economic Zone, Tianjin, 300308, P.R. China.
Exp Anim. 2022 Aug 5;71(3):329-337. doi: 10.1538/expanim.21-0148. Epub 2022 Mar 7.
Traumatic brain injury (TBI) is one of the leading causes of mortality and morbidity worldwide. Tools available for diagnosis and therapy are limited. Small extracellular vesicle (sEV) microRNAs (miRNAs) play an important role in TBI disease progression. This study aimed to investigate the alterations in sEV miRNAs expression in the mouse brain extracellular space after TBI. Twenty-four C57BL/6J mice were randomly divided into two groups (12/group). The TBI group was subjected to all surgical procedures and fluid percussion injury (FPI). The sham group only underwent surgery. Brain specimens were collected 3 h after TBI/sham. The brain sEV were isolated. Differentially expressed miRNAs were identified. A total of 50 miRNAs were observed to be differentially expressed (fold change ≥1.5 and P<0.05) after TBI, including 5 upregulated and 45 downregulated. The major enriched Gene Ontology terms were metabolic processes, cell, intracellular, organelle, cytoplasm, axon, binding, protein kinase activity, protein binding, and protein dimerization activity. The KEGG pathway analysis predicted that the pathways affected by the variation of miRNAs in sEVs after TBI included the Wnt signaling pathway and NF-κB signaling pathway. The changes in five miRNAs were confirmed by qRT-PCR. In conclusion, this study demonstrated the differential expression of a series of miRNAs in brain sEV after TBI, which might be correlated with post-TBI physiological and pathological processes. The findings might also provide novel targets for further investigating the molecular mechanisms underlying TBI and potential therapeutic interventions.
创伤性脑损伤（TBI）是全球范围内导致死亡率和发病率的主要原因之一。现有的诊断和治疗工具有限。细胞外小泡（sEV）微小 RNA（miRNA）在 TBI 疾病进展中起着重要作用。本研究旨在探讨 TBI 后小鼠脑细胞外空间中 sEV miRNA 表达的变化。24 只 C57BL/6J 小鼠被随机分为两组（每组 12 只）。TBI 组接受所有手术程序和液压冲击伤（FPI）。假手术组仅接受手术。TBI/假手术 3 小时后收集脑标本。分离脑 sEV。鉴定差异表达的 miRNA。TBI 后观察到 50 个 miRNA 表达差异（倍数变化≥1.5 和 P<0.05），包括 5 个上调和 45 个下调。主要富集的 GO 术语为代谢过程、细胞、细胞内、细胞器、细胞质、轴突、结合、蛋白激酶活性、蛋白结合和蛋白二聚化活性。KEGG 途径分析预测，TBI 后 sEV 中 miRNA 变化影响的途径包括 Wnt 信号通路和 NF-κB 信号通路。qRT-PCR 验证了五个 miRNA 的变化。总之，本研究表明 TBI 后脑 sEV 中一系列 miRNA 的差异表达可能与 TBI 后的生理和病理过程有关。这些发现也可能为进一步研究 TBI 的分子机制和潜在的治疗干预提供新的靶点。
