Abstract：
Recent evidence showed that general anesthesia produces long-term neurotoxicity and cognitive dysfunction. However, it remains unclear whether maternal non-obstetric surgery under ketamine anesthesia during second trimester causes cognitive impairment in offspring. The present study assigned pregnant rats into three groups: 1) normal control group receiving no anesthesia and no surgery, 2) ketamine group receiving ketamine anesthesia for 2 h on the 14th day of gestation but no surgery, and 3) surgery group receiving abdominal surgery under ketamine anesthesia on the 14th day of gestation. On postnatal day 1, the offspring rats in Ketamine group and surgery group were assigned to receive intra-peritoneal injection of Senegenin (15 mg/kg), once per day for consecutive 14 days. The offspring\'s spatial perception, anxiety-like behavior, and learning and memory were evaluated. Then the offspring\'s hippocampal tissues were collected. The offspring of the surgery group were impaired in the spatial perception in the cliff avoidance test and the spatial learning and memory in the Morris water maze test. Accordingly, the activity of histone deacetylases increased, the protein levels of NEDD9, BDNF, p-TrkB, Syn and PSD-95 decreased, and the density of dendritic spines reduced in the hippocampus of the offspring of the surgery group, and such effects were not seen in the offspring of the ketamine group, neither in the offspring of control group. Senegenin alleviated the learning and memory impairment, and increased the protein levels of NEDD9, BDNF, p-TrkB, Syn and PSD-95 and the density of dendritic spines in the offspring of the surgery group. ketamine anesthesia plus surgery during second trimester impairs hippocampus-dependent learning and memory, and the deficits could be rescued by treatment with Senegenin.
摘要：
最近的证据表明，全身麻醉会产生长期的神经毒性和认知功能障碍。然而,目前尚不清楚妊娠中期在氯胺酮麻醉下的产妇非产科手术是否会导致后代的认知障碍.本研究将孕鼠分为三组:1)正常对照组不接受麻醉和手术,2）氯胺酮组在妊娠第14天接受氯胺酮麻醉2h但不手术，3）手术组在妊娠第14天接受氯胺酮麻醉下的腹部手术。出生后第1天，将氯胺酮组和手术组的子代大鼠分配给腹膜内注射远志皂苷元（15mg/kg），每天一次，连续14天。后代的空间感知，类似焦虑的行为，并对学习和记忆进行了评估。然后收集后代的海马组织。手术组子代在悬崖回避试验中的空间感知和Morris水迷宫试验中的空间学习和记忆受损。因此，组蛋白脱乙酰酶的活性增加，NEDD9，BDNF，p-TrkB,Syn和PSD-95下降，手术组后代海马中树突棘的密度降低，在氯胺酮组的后代中没有看到这种影响，对照组的后代也没有。Senegenin缓解了学习和记忆障碍，增加了NEDD9，BDNF的蛋白质水平，p-TrkB,Syn和PSD-95以及手术组后代的树突棘密度。孕中期氯胺酮麻醉加手术会损害海马依赖性学习和记忆，缺陷可以通过Senegenin治疗来挽救。
