The therapeutic potential of Neural stem cell-derived exosomes in
reducing cerebral ischemic injury: Insights into TLR4/NF-κB pathway
regulation.
Abstract
To explore the mechanism of TLR4/NF-κB regulation of microglia-mediated
inflammation after NSC-Exos transplantation. In this study, a right
middle cerebral artery occlusion model (MCAO) was constructed in SD
rats, NSC-Exos was injected into the lateral ventricle through brain
stereo localization. TAK-242 was given 1 day before MCAO in rats.
Histopathological changes, microglia-mediated inflammatory factor,
colocalized number of CD86/Iba1 and CD206/Iba1 cells, and TLR4/NF-κB
were detected in rats. After brain injury, the number of CD86/Iba1 cells
increased, and the expression of pro-inflammatory factors, TLR4 and
NF-κB were increased. When treatment with NSC-Exos, the number of
CD206/Iba1 cells were increased, and the expression of anti-inflammatory
factors, TLR4 and NF-κB were decreased, promoting anti-inflammatory
phenotype polarization. More importantly, TAK-242 reversed the effect of
NSC-Exos transplantation in animal model. These results suggest that
NSC-Exos can improve the microglia-mediated inflammatory response in
rats with ischemic brain injury, which may be related to the regulation
of TLR4/NF-κB pathway.