Effects and mechanisms of action of hUMSCs-Exos on sevoflurane-induced postoperative cognitive dysfunction and synaptic plasticity impairment in aged mice

OBJECTIVE: To investigate the effects and mechanisms of action of human umbilical cord mesenchymal stem cell (hUMSCs) exosomes (Exos) on sevoflurane-induced postoperative cognitive dysfunction and synaptic plasticity impairment in aged mice. METHODS: Aged C57BL/6 mice were randomly divided into control, sevoflurane, hUMSCs-Exos, antagomiR-NC, and antagomiR-146a-5p groups, with 10 mice in each group. A model of postoperative cognitive dysfunction in aged mice was established by continuous inhalation of 3% sevoflurane for 3 h, followed by injection of hUMSCs-Exos into the lateral ventricle. The Morris water maze was used to assess cognitive function in mice; hematoxylin-eosin (HE) staining and Nissl staining were used to detect hippocampal pathological injury in mice; Golgi staining was used to detect dendritic spine density in mice; Western blotting was used to detect the protein expression levels of methyl-CpG-binding protein (MeCP)2, postsynaptic density protein (PSD)-95, growth-associated protein (GAP)-43, synaptophysin (Syn), Toll-like receptor (TLR)4, myeloid differentiation factor (MyD)88, and nuclear factor (NF)-κB in mouse hippocampal tissue; reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect miR-146a-5p expression in hUMSCs-Exos transfected with antagomiR-NC and antagomiR-146a-5p. RESULTS: Administration of hUMSCs-Exos significantly ameliorated sevoflurane-induced cognitive dysfunction, hippocampal neuronal injury, and hippocampal synaptic plasticity impairment in aged mice and inhibited activation of the TLR4/MyD88/NF-κB signaling pathway in mouse hippocampal tissue (P<0.05). Administration of hUMSCs-Exos with miR-146a-5p inhibited significantly reversed the ameliorative effects of hUMSCs-Exos on sevoflurane-induced cognitive dysfunction, hippocampal injury, and synaptic plasticity impairment in aged mice (P<0.05). CONCLUSIONS: hUM-SCs-Exos may inhibit activation of the TLR4/MyD88/NF-κB signaling pathway by delivering miR-146a-5p, thereby ameliorating sevoflurane-induced cognitive dysfunction, hippocampal injury, and synaptic plasticity impairment in aged mice.