OBJECTIVES Cortical neuron-released exosomes have been demonstrated to block inflammasome activation in the central nervous system. This study aimed to investigate whether cortical neuron-released exosomal microRNA-181c-3p (miR-181c-3p) affected ischemic brain injury (IBI). METHODS An IBI rat model was established by middle cerebral artery occlusion (MCAO). Astrocytes collected from rats were exposed to exosomes derived from cortical neurons to investigate the effect of exosomes on chemokine (C-X-C motif) ligand 1 (CXCL1) expression and inflammatory response. Then, ectopic expression was induced in astrocytes treated with oxygen and glucose deprivation (OGD). RESULTS CXCL1 was identified to be an upregulated gene in IBI by microarray-based gene expression profiling. Additionally, upregulation of CXCL1 and promoted inflammatory response was also found in MCAO rats. miR-181c-3p was downregulated in OGD-treated cortical neurons and exosomes derived from OGD-treated cortical neurons. Exosomes derived from OGD-treated cortical neurons decreased the expression of CXCL1 and inflammatory factors in astrocytes, and exosomes delivered miR-181c-3p to decrease CXCL1 expression in astrocytes. CXCL1 was a target gene of miR-181c-3p. Delivery with miR-181c-3p mimic and siRNA against CXCL1 (si-CXCL1) was shown to inhibit inflammation in astrocytes by downregulating CXCL1. CONCLUSION Collectively, exosomal miR-181c-3p derived from cortical neurons exerts protective effects on neuroinflammation in astrocytes via downregulation of CXCL1 in an IBI rat model.

中文翻译：

---

皮质神经元衍生的外泌体 MicroRNA-181c-3p 通过下调缺血性脑损伤大鼠模型星形胶质细胞中的 CXCL1 来抑制神经炎症。


目的 皮质神经元释放的外泌体已被证明可以阻断中枢神经系统中炎症小体的激活。本研究旨在探讨皮质神经元释放的外泌体 microRNA-181c-3p (miR-181c-3p) 是否影响缺血性脑损伤 (IBI)。方法采用大脑中动脉闭塞(MCAO)法建立IBI大鼠模型。将收集自大鼠的星形胶质细胞暴露于源自皮质神经元的外泌体，以研究外泌体对趋化因子（CXC基序）配体1（CXCL1）表达和炎症反应的影响。然后，在氧糖剥夺（OGD）处理的星形胶质细胞中诱导异位表达。结果 通过基于微阵列的基因表达谱分析，CXCL1 被鉴定为 IBI 中上调的基因。此外，在 MCAO 大鼠中还发现 CXCL1 上调并促进炎症反应。 miR-181c-3p 在 OGD 处理的皮质神经元和源自 OGD 处理的皮质神经元的外泌体中下调。来自OGD处理的皮质神经元的外泌体降低了星形胶质细胞中CXCL1和炎症因子的表达，并且外泌体递送miR-181c-3p以降低星形胶质细胞中CXCL1的表达。 CXCL1是miR-181c-3p的靶基因。研究表明，使用 miR-181c-3p 模拟物和针对 CXCL1 (si-CXCL1) 的 siRNA 进行递送可通过下调 CXCL1 来抑制星形胶质细胞中的炎症。结论 总的来说，在 IBI 大鼠模型中，来自皮质神经元的外泌体 miR-181c-3p 通过下调 CXCL1 对星形胶质细胞的神经炎症发挥保护作用。