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- W2912076894 abstract "Recent evidence has shown that general anaesthesia can cause long-term neurotoxicity and cognitive dysfunction1. Ketamine is commonly used in paediatric anaesthesia and antidepressant therapy. Increasing data indicate that ketamine can induce neuronal degeneration and learning and memory impairment2. Whether maternal non-obstetric surgery under ketamine anaesthesia in the middle stage of pregnancy causes cognitive impairment in offspring is unclear. The aim of our study was to evaluate the effect of maternal abdominal surgery under ketamine anaesthesia on cognition in the offspring and the underlying mechanisms of any change. Thirty pregnant Sprague–Dawley (SD) rats were randomly assigned to three groups: ketamine anaesthesia (Ket group), abdominal surgery under ketamine anaesthesia (Ket+Surg group), and control. On day 14 of gestation, pregnant rats in the Ket group received ketamine anaesthesia for 2 h, whereas those in the Ket+Surg group underwent abdominal surgery under ketamine anaesthesia; the total time of anaesthesia and operation was 2 h. Equal volumes of saline were given to the control group. Offspring were intraperitoneally injected with traditional Chinese medicine (SEN), histone deacetylase 2 (HDAC2) inhibitor suberoylanilide hydroxamic acid (SAHA), or dimethyl sulfoxide (DMSO) once per day from day 1 after birth, for 14 consecutive days. The cliff avoidance, open field, passive avoidance, and Morris water maze (MWM) test were used to evaluate spatial perception, anxiety-like behaviour, non-spatial and spatial learning, and memory function on days 7, 22, 23, and 30, respectively. The day after the MWM test, the hippocampus was collected for detection of the activity of histone deacetylases (HDACs) and histone acetyltransferases (HATs), the expression levels of developmentally down-regulated 9 (NEDD9) and postsynaptic density 95 (PSD-95) mRNA and protein, and the density and type of dendritic spines with ultraviolet spectrophotometry, quantitative PCR (Q-PCR), western blot, and Golgi stain respectively. Cliff avoidance test showed that the scores in the Ket+Surg group decreased significantly when compared with those in the control group. The results of open field and passive avoidance test showed no significant changes among the three groups. Compared with the control group, the escape latency increased, whereas platform-crossing times and target quadrant traveling time decreased in the Ket+Surg group. Surgery under ketamine anaesthesia enhanced the activity of HDACs, decreased the protein levels of NEDD9 and PSD-95, and the density of dentritic spine; however, it did not change the activity of HATs, the mRNA levels of NEDD9 and PSD-95, and the type of dentritic spine. All these indexes in the Ket group showed no significant changes. SEN decreased escape latency, whereas it increased platform-crossing times, target quadrant traveling time, the protein levels of NEDD9 and PSD-95, and the density of dentritic spine in surgery exposure rat offspring. SAHA showed no obvious effect on these indexes. Ketamine anaesthesia in the middle stage of pregnancy has no effect on cognition, but abdominal surgery under ketamine anaesthesia impairs spatial perception and spatial learning and memory in offspring; this is associated with up-regulation of HDACs activity, down-regulation of the protein levels of NEDD9 and PSD-95, and the density of dentritic spine. SEN can mitigate the spatial learning and memory impairments caused by abdominal surgery under ketamine anaesthesia." @default.
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- W2912076894 date "2019-03-01" @default.
- W2912076894 modified "2023-09-26" @default.
- W2912076894 title "Effects of non-obstetric surgery under ketamine anaesthesia in the middle stage of pregnancy on cognition in the offspring and underlying mechanisms" @default.
- W2912076894 doi "https://doi.org/10.1016/j.bja.2018.10.008" @default.
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