术后认知功能障碍
KEAP1型
海马体
莱菔硫烷
医学
伏隔核
异氟醚
前额叶皮质
发病机制
内科学
神经科学
麻醉
内分泌学
作者
Dongyu Hua,Ailin Luo,Zifeng Wu,Chaoli Huang,Shan Li,Xiaolin Xu,Jiali Xu,Chun Yang,Di Wang,Cunming Liu
标识
DOI:10.1016/j.brainresbull.2022.01.005
摘要
Anesthesia and surgery are likely causing cognitive dysfunction in patients, especially the elderly. However, the underlying pathogenic mechanisms largely remain unclear. Accumulating evidence suggest that signaling between Kelch-like erythroid cell-derived protein with CNC homology (ECH)-associated protein 1 (Keap1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) plays an important role in the pathogenesis and treatment of brain dysfunction, while sulforaphane (SFN), a natural compound acting as an Nrf2 agonist, can improve brain function. In the present study, we used 9-month-old mice to perform tibial fracture surgery under isoflurane general anesthesia. Hierarchical cluster analysis of Morris water maze test (MWMT) analysis was performed to classify mice into post-operative cognitive dysfunction (POCD) versus non-POCD phenotypes. Expression levels of Keap1 and Nrf2 were significantly decreased in the medial prefrontal cortex (mPFC), hippocampus and liver, but not in the nucleus accumbens, muscle and gut of POCD mice compared to control and non-POCD mice. Interestingly, both pretreatment and posttreatment with SFN significantly improved the abnormal behaviors of mice in the MWMT, in parallel with the up-regulated levels of Keap1-Nrf2 signaling in the mPFC, hippocampus and liver. In conclusion, these results suggest that decreased Keap1-Nrf2 signaling in the mPFC, hippocampus and liver may contribute to the onset of POCD, and that SFN exerts facilitating effects on POCD symptoms by increasing Keap1-Nrf2 signaling. • Keap1-Nrf2 decreases in mPFC, hippocampus of brain and liver in POCD model. • Sulforaphane improves abnormal behaviors of POCD. • Sulforaphane restores COPD cognition by increasing Keap1-Nrf2.
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