Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Eur Rev Med Pharmacol Sci. 2023 Apr;27(7):2776-2785. doi: 10.26355/eurrev_202304_31908.
Brain development is susceptible to external influences during the gestation period so the neurotoxicity of anesthetics has gained a lot of attention. We aimed to investigate the neurotoxicity of sevoflurane to fetal mice brain as well as the neuroprotective effects of dexmedetomidine.
Pregnant mice were treated with 2.5% sevoflurane for 6 hours. The changes in fetal brain development were assayed with immunofluorescence and western blot. The pregnant mice were intraperitoneally injected with dexmedetomidine or vehicle from gestation day (G) 12.5 to G15.5.
Our results showed maternal sevoflurane exposure could not only inhibit neurogenesis but also lead to precocious generation of astrocytes in fetal mice brains. The fetal mice brain of sevoflurane group exhibited a significant inhibition in the activity of Wnt signaling and the expression of CyclinD1, Ngn2. Chronic dexmedetomidine administration could minimize the negative effects caused by sevoflurane by activating the Wnt signaling pathway.
This study has uncovered a Wnt signaling-related mechanism of the neurotoxicity of sevoflurane and confirmed the neuroprotective effect of dexmedetomidine, which could provide pre-clinical evidence for clinical decision-making.
脑发育在妊娠期易受外界影响，因此麻醉药的神经毒性受到了广泛关注。本研究旨在探讨七氟醚对胎鼠脑的神经毒性作用以及右美托咪定的神经保护作用。
将妊娠小鼠用 2.5%七氟醚处理 6 小时。用免疫荧光和 Western blot 检测胎鼠脑发育变化。从妊娠第 12.5 天至第 15.5 天，给妊娠小鼠腹腔内注射右美托咪定或载体。
本研究结果表明，母体七氟醚暴露不仅能抑制神经发生，还能导致胎鼠脑内星形胶质细胞早熟。七氟醚组胎鼠脑内 Wnt 信号活性显著抑制，CyclinD1、Ngn2 表达减少。慢性右美托咪定给药可通过激活 Wnt 信号通路，减轻七氟醚引起的负性影响。
本研究揭示了七氟醚神经毒性的 Wnt 信号相关机制，并证实了右美托咪定的神经保护作用，为临床决策提供了临床前证据。
