The interaction between astrocytes and microglia plays a vital role in the damage and repair of brain lesions due to traumatic brain injury (TBI). Recent studies have shown that exosomes act as potent mediators involved in intercellular communication. In the current study, the expression of inflammatory factors and miR-873a-5p in the lesion area and oedema area was evaluated in 15 patients with traumatic brain injury. Exosomes secreted by astrocytes were detected by immunofluorescence, Western blot and electron microscopy. A mouse model of TBI and an in vitro model of LPS-induced primary microglia were established to study the protective mechanism of exosomes from miR-873a-5p overexpressing in TBI-induced nerve injury. We discovered that exosomes derived from activated astrocytes promote microglial M2 phenotype transformation following TBI. More than 100 miRNAs were detected in these astrocyte-derived exosomes. miR-873a-5p is a major component that was highly expressed in human traumatic brain tissue. Moreover, miR-873a-5p significantly inhibited LPS-induced microglial M1 phenotype transformation and the subsequent inflammation through decreased phosphorylation of ERK and NF-κB p65. This effect also greatly improved the modified neurological severity score (mNSS) and attenuated brain injury in a strictly controlled cortical impact mouse model. Taken together, our research indicates that miRNAs in the exosomes derived from activated astrocytes play a key role in the astrocyte-microglia interaction. miR-873a-5p, as one of the main components of these astrocyte-derived exosomes, attenuated microglia-mediated neuroinflammation and improved neurological deficits following TBI by inhibiting the NF-κB signalling pathway. These findings suggest a potential role for miR-873a-5p in treating traumatic brain injury.

中文翻译：

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富含miR-873a-5p的星形胶质细胞外泌体通过颅脑外伤后的小胶质细胞表型调节来抑制神经炎症

星形胶质细胞与小胶质细胞之间的相互作用在创伤性脑损伤（TBI）引起的脑部损伤的修复中起着至关重要的作用。最近的研究表明，外泌体是参与细胞间通讯的有效介体。在本研究中，评估了15例脑外伤患者炎性因子和miR-873a-5p在病变区域和水肿区域的表达。通过免疫荧光，蛋白质印迹和电子显微镜检测星形胶质细胞分泌的外泌体。建立了TBI小鼠模型和LPS诱导的原发性小胶质细胞体外模型，以研究miR-873a-5p过表达的外泌体在TBI诱导的神经损伤中的保护机制。我们发现，来自活化星形胶质细胞的外泌体在TBI后促进小胶质细胞M2表型转化。在这些星形胶质细胞来源的外泌体中检测到100多个miRNA。miR-873a-5p是在人类创伤性脑组织中高度表达的主要成分。此外，miR-873a-5p通过减少ERK和NF-κBp65的磷酸化，显着抑制LPS诱导的小胶质M1表型转化和随后的炎症。在严格控制的皮质撞击小鼠模型中，该作用还大大改善了改良的神经系统严重程度评分（mNSS）并减轻了脑损伤。两者合计，我们的研究表明，来自活化星形胶质细胞的外泌体中的miRNA在星形胶质细胞-小胶质细胞相互作用中起关键作用。miR-873a-5p作为这些星形胶质细胞来源外泌体的主要成分之一，通过抑制NF-κB信号通路，减轻了TBI后小胶质细胞介导的神经炎症，改善了神经功能缺损。这些发现表明，miR-873a-5p在治疗颅脑损伤中具有潜在作用。