Effect Of Sevoflurane Inhalation Anesthesia On Perioperative Neurocognitive Disorders By Promoting Astrocyte Activation

Objective:To study the effects of sevoflurane inhalation anesthesia on perioperative neurocognitive disorders in elderly mice,and to explore the mechanism of activation of astrocytes in perioperative neurocognitive disorders of sevoflurane inhaled anesthesia mice.Methods:144 male SPF male C57BL/6 mice,aged 16 to 18 months,weighing 40 to 45 g,were divided into 4 groups using a random number table,36 in each group,namely（group C）,sevoflurane group（Group P）,surgery group（S group）,sevoflurane+surgery group（PS group）.Sham surgery was performed respectively,3.5%sevoflurane inhalation for 2h,30%O₂ inhalation for 2h+tibial fracture incision and reduction internal fixation surgery,3.5%sevoflurane inhalation and reduction internal fixation surgery for 2h.Y-maze experiments were performed 1d before each group to evaluate the ability of the mice to have working memory before operation.Thus,Morris water maze experiments were performed on 1d,3d,and 7d to evaluate the spatial learning and memory ability of the mice in each group.After 1d,3d,and 7d behavioral cognitive evaluation experiments,12 mice were randomly selected from each group and sacrificed.Hippocampal tissue was taken and immunofluorescent staining was used to determine the hippocampal glia morphology and GFAP expression levels in each group;DCFH-DA method was used to measure hippocampal reactive oxygen species（ROS）level;chemical colorimetric method was used to measure hippocampal succinate dehydrogenase（SDH）activity;luminescence method was used to measure hippocampal ADP and ATP levels to calculate ADP/ATP.Results:There was no significant difference in the body weight of mice in each group（P>0.05）.There was also no significant difference in the time required for mice to reach the learning standard,the number of false reaction times throughout the day,and the total reaction time throughout the day in mice in a Y-maze experiment 1d before surgery（P>0.05）.Compared with group C,in the Morris water maze experiment on the 1st and 3d postoperative days,the escape latency was prolonged（P<0.05）,the target quadrant stay was shortened（P<0.05）,and the number of puncture times was reduced（P<0.05）.The time to reach the target quadrant was longer（P<0.05）,compared with group C,the escape latency was longer at 7 days after surgery（P<0.05）,the target quadrant stay was shortened（P<0.05）,and the number of crossings was reduced（P<0.05）,the time to reach the target quadrant is longer（P<0.05）.Compared with group P and S,in the PS group,Morris water maze experiments at 1d,3d,and 7d after surgery showed that the incubation period was longer（P<0.01）,and the target quadrant stay was significantly shorter（P<0.01）,Significantly reduced（P<0.01）,significantly longer time to reach the target quadrant（P<0.01）,and reduced spatial learning and memory abilities,Immunofluorescence experiments and energy metabolism-related experiments at 1d,3d,and 7d after operation showed that compared with group C,the number of glial fibrillary acidic protein（GFAP）positive cells in the hippocampal region increased at 1d and 3d after operation（P<0.05）,increased release of reactive oxygen species（ROS）（P<0.05）,decreased succinate dehydrogenase（SDH）activity（P<0.05）,and increased adenosine diphosphate/adenosine triphosphate（ADP/ATP）（P<0.05）,Compared with group C,group S had higher GFAP-positive cell counts（P<0.05）,increased ROS release（P<0.05）,decreased SDH activity（P<0.05）,and increased ADP/ATP on day 7 after surgery.（P<0.05）.Compared with the P and S groups,the GFAP-positive cell counts in the hippocampal region of the PS group increased significantly on the 1st,3d,and7th days after the operation（P<0.01）,the ROS release was significantly increased（P<0.01）,and the SDH activity Significantly decreased（P<0.01）,and ADP/ATP increased significantly（P<0.01）.Conclusion:Inhalation anesthesia with 3.5%sevoflurane can cause perioperative neurocognitive disorders in elderly mice.This may be because inhalation anesthesia with sevoflurane can promote the activation of astrocytes in mice and affect the energy metabolism in the hippocampus.