| Abstract: | AIM To investigate the effect of dexmedetomidine (DEX) on perioperative neurocognitive disorders (PND) in aged mice and its mechanism. METHODS The PND animal model was established by hepatic left lateral lobectomy in C57BL/6J aged mice, and the effects of intraoperative DEX intervention on postoperative cognitive behavior in aged mice were evaluated by Morris water maze and Y maze experiments. The effects of intraoperative DEX intervention on the changes of neurons in hippocampal CA1 region of aged mice were observed by Nissl staining and TUNEL staining. The effect of intraoperative DEX intervention on long-term potentiation in hippocampal CA1 region was recorded by patch-clamp technique. The effects of intraoperative DEX intervention on hippocampal astrocyte activation in aged mice were detected by immunofluorescence and immunohistochemistry. The effects of intraoperative DEX intervention on the protein levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and cleaved caspase-3 in hippocampal CA1 region of aged mice were determined by Western blot. RESULTS Intraoperative DEX intervention attenuated postoperative cognitive dysfunction in aged mice (P<0.01). Intraoperative DEX intervention significantly inhibited surgery-induced hippocampal neuron loss (P<0.01), reversed surgery-induced decrease in field excitatory postsynaptic potential amplitude, and reduced surgery-induced increases in the protein levels of TNF-α, IL-6 and cleaved caspase-3 in hippocampal CA1 region of aged mice (P<0.01). CONCLUSION Dexmedetomidine protects hippocampal neurons and improves postoperative cognitive function in aged mice by inhibiting hippocampal astrocyte activation and reducing neuronal inflammation and neuronal apoptosis. |
