Exosome-shuttled miR-672-5p from anti-inflammatory microglia repair traumatic spinal cord injury by inhibiting AIM2/ASC/Caspase-1 signaling pathway mediated neuronal pyroptosis

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.