Ectomesenchymal Stem Cell Transplantation Induces Microglial Polarization and Anti-inflammatory IL-10 Secretion via NF-κB and MAPK Pathways to Mitigate Brain Injury Post-cerebral Hemorrhage.

Intracerebral hemorrhage (ICH) has poor clinical outcomes, with microglia-induced neuroinflammation being a key pathological process. This study investigated the therapeutic potential of ectomesenchymal stem cells (EMSCs) from the nasal mucosa in ICH. Using a mouse ICH model, we transplanted EMSCs intracranially. We assessed neurological function, neuronal survival, microglial polarization, and inflammatory responses. In vitro, we co-cultured EMSCs with hemin-stimulated microglia and performed transcriptomic analysis. Key proteins in the NF-κB and MAPK pathways were evaluated in vivo based on in vitro findings. EMSC transplantation significantly improved neurological deficits and reduced neuronal injury. It promoted microglial polarization towards the anti-inflammatory M2 phenotype and increased levels of the anti-inflammatory cytokine IL-10. Mechanistically, EMSCs suppressed the activation of the NF-κB and MAPK signaling pathways in microglia. Our findings demonstrate that EMSCs alleviate neuroinflammation and neural injury after ICH by modulating microglial polarization, potentially via inhibiting the NF-κB and MAPK pathways. This suggests EMSCs as a promising novel therapy for hemorrhagic stroke.