Olfactory Mucosa MSCs-Derived Exosomal RPL6 Attenuates Seizure-Induced Neuronal Damage via FGF2-Mediated Oxidative Stress and Mitophagy

Evidence suggests that olfactory mucosa-derived mesenchymal stem cells (OM-MSCs) can benefit epilepsy treatment in both clinical patients and mouse models, although their precise mechanism remains unclear. Given the advantages of exosomes in precise cellular regulation, ease of storage, and long-term stability, this study investigated the role of OM-MSCs-derived exosomes (OM-MSCs-exos) in status epilepticus (SE) models. Here, SE mouse models were induced by intraperitoneal injection of pilocarpine. OM-MSCs, differentially treated OM-MSCs-exos, and recombinant FGF2 protein were injected into SE model mice to investigate the effects of OM-MSCs-exos on SE models and their potential mechanisms. Functionally, treatment with OM-MSCs and OM-MSCs-exos significantly improved cognitive function, as evidenced by increased target quadrant duration, decreased escape latency, increased average speed, and more platform crossings in behavioral tests. Furthermore, this treatment further alleviated hippocampal tissue damage by reversing pilocarpine-induced oxidative damage, neuronal injury, and excessive mitophagy. Consistent outcomes were confirmed in vitro. Mechanistically, RPL6 was screened and confirmed as a key protein in OM-MSCs-exos, which interacts with FGF2 to promote FGF2 expression, thereby alleviating oxidative stress and mitochondrial dysfunction induced by H₂O₂. In conclusion, the RPL6 protein derived from OM-MSCs-exos improves neuronal damage post-SE by activating FGF2 to suppress oxidative stress and mitophagy, laying a theoretical foundation for the development of exosome-related drugs for treating epilepsy clinically.