Small extracellular vesicles encapsulating CCL2 from activated astrocytes induce microglial activation and neuronal apoptosis after traumatic spinal cord injury

Journal of Neuroinflammation

Dongdong Jiang¹  Chengyue Ji¹  Zhuanghui Wang¹  Guoyong Yin¹  Jin Fan¹  Wei Liu¹  Weihua Cai¹  Xuhui Ge¹  Pengyu Tang¹  Wu Ye¹  Jiaxing Wang¹  Yuluo Rong¹ 

[1] Department of Orthopaedics, First Affiliated Hospital of Nanjing Medical University, 210029, Nanjing, Jiangsu, China;

关键词: Spinal cord injury;    Astrocyte;    Small extracellular vesicles;    CCL2;    Microglia;    Neuron;   

DOI  :  10.1186/s12974-021-02268-y

来源: Springer

【 摘 要 】

BackgroundSpinal 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.MethodsElectron 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.ResultsOur 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.ConclusionThis 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.

【 授权许可】

CC BY