Dexmedetomidine-mediated neuroprotection against sevoflurane-induced brain development abnormality in fetal mice brain.

Abstract

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.