Pregnant Mice Inhale Isoflurane Causes Neuroinflammation In Fetal Mice And Cognitive Dysfunction In Offspring Mice

Background and Purpose:Inhalation anesthetics induce neurotoxic effects, especially on the development of the brain, has become a hot issue of Anesthesiology community and the public. The Neuroinflammation induced by Inhalation anesthetics maybe cause neurotoxicity on developing brain through the apoptotic pathway. This study was to investigate the effects of neuroinflammation in fetal mice and learning and memory function in offspring mice caused by inhalation of isoflurane during pregnancy, the neuroprotection of propofol on isoflurane anesthesia.Material and methods:Three month-old C57BL/6 male and female mice mated in 2: 1 to get pregnant mice. At gestational day 15 (G15), using a random number table, the pregnant mice were randomly assigned into three groups:a. isoflurane group: inhalation of 1.4% isoflurane+100% O2 for 2 hours; b. propofol-pretreatment group: intraperitoneal injection of propofol 50mg/kg,30 minutes later, inhalation of 1.4% isoflurane+100% O2 for 2 hours; c. control group:inhalation of 100%O2 for 2 hours. Total brain tissue of G15 fetal mice was subject to assay interleukin-6 expression levels and fresh hippocampal tissue of postnatal day 31 (P31) offspring mice was subject to assay PSD-95 expression level using western blot analysis. Immunohistochemistry was used to assay the synaptophysin expression level in hippocampus of P31 offspring mice. In addition, we used Morris water maze to test the learning and memory function of P31 offspring mice produced by pregnant mice received the same experimental treatments at G15.Results:Isoflurane anesthesia at gestational day 15 increased interleukin-6 level (217.07%±50.68% vs 100.00%±5.32%, P<0.01) in fetal mice and reduced postsynaptic density-95 (31.62%±2.25% vs 100.00%±2.97%, P<0.001) and synaptophysin (73.04%±7.35% vs 100%±3.00%, P=0.002) in offspring mice at postnatal day 31. Propofol attenuated the isoflurane-induced increases in interleukin-6 (118.93%±3.94% vs 217.07%±50.68%, P=0.023) in fetal mice, reductions of postsynaptic density-95 (48.44%±3.76% vs 31.62%±2.25%, P=0.002) and synaptophysin (87.60%±3.10% vs 73.04%±7.35%, P=0.033) in offspring mice at postnatal day 31. Neurotoxicity caused by isoflurane anesthesia impaired performances at Morris water maze test in offspring mice at postnatal day 36:mean escape latency time increased (56.51s±27.13s vs 34.26s±18.33s, P<0.01), platform crossing times decreased [(median,1; interquartile range,1) vs (median,6; interquartile range,3), P<0.001]. P36 offspring mice in propofol-pretreatment group had better performances at Morris water maze test than those in isoflurane group:mean escape latency time (31.29s±23.94s vs 56.51s±27.13s, P=0.01), platform crossing times [(median,3; interquartile range,2) vs (median,1; interquartile range,1), P=0.002].Conclusions:The inhalation of isoflurane during pregnancy may induce neuroinflammation in fetal mice. Neurotoxicity caused by neuroinflammation maybe impair learning and memory function in offspring mice. Propofol might attenuate isoflurane-induced neuroinflammation and neurotoxicity in fetal mice and offspring mice.