创伤性脊髓损伤(TSCI)是一种毁灭性的中枢神经系统创伤性疾病,导致运动和感觉功能的难治性丧失。到目前为止,TSCI没有有效的治疗方法。最近,然而,来自各种脊髓细胞的纳米外泌体在治疗各种疾病方面显示出巨大的前景,包括TSCI。小胶质细胞是脊髓微环境的组成部分之一。抗炎小胶质细胞(M2)已被证明可以抑制炎症并促进TSCI后脊髓的功能恢复。然而,M2小胶质细胞外泌体中microRNAs(miRNAs)在TSCI治疗中的作用尚不清楚.在这项研究中,我们研究了M2小胶质细胞外泌体(M2-Exos)是否比M0小胶质细胞外泌体(Exos)更好地促进TSCI小鼠的功能行为恢复。与Exos相比,发现M2-Exos在促进功能行为恢复方面具有更好的效果,促进轴突再生,降低TSCI后脊髓神经元的焦突水平。通过一系列的实验,我们还证实miR-672-5p是与M2-Exos相关的最关键的miRNA,它的靶向基因是AIM2。富含miR-672-5p的M2-Exos可以通过抑制AIM2活性来抑制AIM2/ASC/caspase-1信号通路,从而抑制TSCI小鼠神经元的焦亡,最终促进其功能行为的恢复。总之,我们的研究表明,M2-Exos的应用可能是一种有前景的TSCI治疗策略.
Traumatic spinal cord injury (TSCI) is a devastating traumatic disease of the central nervous system, which leads to refractory loss of motor and sensory function. So far, there is no effective treatment for TSCI. Recently, however, nano-sized exosomes from various spinal cord cells have shown great prospects in the treatment of various diseases, including TSCI. Microglia are one of the components of the spinal cord microenvironment. Anti-inflammatory microglia (M2) have been shown to inhibit inflammation and promote the functional recovery of spinal cord after TSCI. However, the role micro RNAs (miRNAs) in exosomes derived from M2 microglia in the treatment of TSCI is unclear. In this study, we investigated whether M2 microglial exosomes (M2-Exos) could better promote the functional behavior recovery of mice with TSCI than M0 microglial exosomes (Exos). Compared with Exos, M2-Exos were found to have a better effect in promoting the recovery of functional behavior, promoting axon regeneration and reducing the level of pyroptosis of spinal cord neurons after TSCI. Through a series of experiments, we also confirmed that miR-672-5p is the most critical miRNA associated with M2-Exos, and that its targeting gene is AIM2. M2-Exos rich in miR-672-5p could inhibit the AIM2/ASC/caspase-1 signaling pathway by inhibiting AIM2 activity, so as to inhibit neuronal pyroptosis and finally promote the recovery of functional behavior in mice with TSCI. In conclusion, our study suggests that the application of M2-Exos may be a promising treatment strategy for TSCI.