Spinal cord injury (SCI) is a severe traumatic disease which causes high disability and mortality rates. The molecular pathological features after spinal cord injury mainly involve the inflammatory response, microglial and neuronal apoptosis, abnormal proliferation of astrocytes, and the formation of glial scars. However, the microenvironmental changes after spinal cord injury are complex, and the interactions between glial cells and nerve cells remain unclear. Small extracellular vesicles (sEVs) may play a key role in cell communication by transporting RNA, proteins, and bioactive lipids between cells. Few studies have examined the intercellular communication of astrocytes through sEVs after SCI. The inflammatory signal released from astrocytes is known to initiate microglial activation, but its effects on neurons after SCI remain to be further clarified. Electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were applied to characterize sEVs. We examined microglial activation and neuronal apoptosis mediated by astrocyte activation in an experimental model of acute spinal cord injury and in cell culture in vitro. Our results indicated that astrocytes activated after spinal cord injury release CCL2, act on microglia and neuronal cells through the sEV pathway, and promote neuronal apoptosis and microglial activation after binding the CCR2. Subsequently, the activated microglia release IL-1β, which acts on neuronal cells, thereby further aggravating their apoptosis. This study elucidates that astrocytes interact with microglia and neurons through the sEV pathway after SCI, enriching the mechanism of CCL2 in neuroinflammation and spinal neurodegeneration, and providing a new theoretical basis of CCL2 as a therapeutic target for SCI.

中文翻译：

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从活化的星形胶质细胞包裹 CCL2 的小细胞外囊泡在创伤性脊髓损伤后诱导小胶质细胞活化和神经元凋亡

脊髓损伤 (SCI) 是一种严重的创伤性疾病，可导致高致残率和死亡率。脊髓损伤后的分子病理特征主要涉及炎症反应、小胶质细胞和神经元凋亡、星形胶质细胞异常增殖、胶质瘢痕形成等。然而，脊髓损伤后的微环境变化复杂，神经胶质细胞与神经细胞之间的相互作用尚不清楚。小细胞外囊泡 (sEV) 可能通过在细胞之间运输 RNA、蛋白质和生物活性脂质在细胞通讯中发挥关键作用。很少有研究检查 SCI 后星形胶质细胞通过 sEV 进行的细胞间通讯。已知从星形胶质细胞释放的炎症信号会启动小胶质细胞激活，但其对 SCI 后神经元的影响仍有待进一步阐明。应用电子显微镜 (TEM)、纳米粒子跟踪分析 (NTA) 和蛋白质印迹来表征 sEV。我们在急性脊髓损伤的实验模型和体外细胞培养中检查了由星形胶质细胞激活介导的小胶质细胞激活和神经元凋亡。我们的研究结果表明，脊髓损伤后激活的星形胶质细胞释放 CCL2，通过 sEV 通路作用于小胶质细胞和神经元细胞，结合 CCR2 后促进神经元凋亡和小胶质细胞活化。随后，活化的小胶质细胞释放IL-1β，作用于神经元细胞，从而进一步加剧其凋亡。本研究阐明了 SCI 后星形胶质细胞通过 sEV 通路与小胶质细胞和神经元相互作用，