Olfactory Mucosa Mesenchymal Stem Cells ( <scp>OM</scp> ‐ <scp>MSCs</scp> )‐Derived Exosomes Mitigate Neuroinflammation and Nerve Injury After Intracranial Hemorrhage ( <scp>ICH</scp> ) Through <scp>miR</scp> ‐30‐5p and Its Associated Mechanisms

Exosomes derived from olfactory mucosa mesenchymal stem cells (OM-MSCs-EXOs) offer a novel therapeutic strategy for various diseases due to their role in regulating intercellular signaling. However, the potential of OM-MSCs-EXOs to improve intracranial hemorrhage (ICH) and its underlying mechanisms is unclear. In this study, we found that OM-MSCs-EXOs can perfect neurofunctional recovery after ICH. The level of miR-30b-5p declined in thrombin-triggered OM-MSCs. Suppression of miR-30b-5p in OM-MSCs-EXOs inhibited mitophagy and promoted reactive oxygen species (ROS) and inflammasome-related protein levels. Moreover, downregulation of miR-30b-5p in OM-MSCs-EXOs inhibited HT22 cell viability and promoted apoptosis and inflammation. Mechanistically, miR-30b-5p targeted SENP5 and decreased the level of SENP5. SENP5 silencing upregulated SUMO2/3-conjugated METTL3 and downregulated METTL3 levels. METTL3 silencing inhibited LPA1 levels by inhibiting m6A modifications. Further, SUMOylated METTL3 was decreased and the m6A level of LPA1 was enhanced in thrombin-triggered BV2 cells, which was abolished by OM-MSCs-EXOs, and this phenomenon was reversed by miR-30b-5p silenced-OM-MSCs-EXOs. This work confirmed the potential of OM-MSCs-EXOs mediated delivery of miR-30b-5p in relieving ICH via the SENP5/METTL3/LPA1 axis.