ABSTRACT
Objective:To evaluate the effect of surgery under propofol anesthesia during mid-pregnancy on the cognitive function and hippocampal histone deacetylase 2 (HDAC2)-cAMP response element-binding protein (CREB)-N-methyl-D-aspartate (NMDA) receptor 2B subunit (NR2B)-containing NMDA receptor (NR2B) signaling pathway in the offspring rats.Methods:Thirty healthy Sprague-Dawley rats at 14 days of gestation were divided into 3 groups ( n=10 each) using a random number table method: propofol anesthesia group (P group), surgery under propofol anesthesia group (S group) and control group (C group). In S group, propofol 20 mg/kg was injected via the caudal vein, and then propofol was continuously infused at a rate of 20 mg·kg -1·h -1 to maintain anesthesia for 4 h, and exploratory laparotomy was performed. Group P received no exploratory laparotomy and the other treatments were similar to those previously described in group S. The equal volume of normal saline was given instead in group C. The learning and memory of the offspring rats was assessed using Morris water maze test on postnatal day 30. The expression of HDAC2, phosphorylated CREB (p-CREB), NR2B, brain-derived neurotriphic factor (BDNF) and phosphorylated tyrosine kinase B (p-TrkB) in offspring′s hippocampi was evaluated by Western blot. Apoptosis in hippocampal neurons was detected by TUNEL staining. Results:Compared with group C, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the time spent in the second quadrant was shortened, the expression of HDAC2 was up-regulated, the expression of p-CREB, NR2B, BDNF and p-TrkB was down-regulated, and the apoptosis rate of the hippocampal neurons was increased in P and S groups ( P<0.05). Compared with P group, the escape latency was significantly prolonged, the frequency of crossing the original platform was decreased, the time spent in the second quadrant was shortened, the expression of HDAC2 was up-regulated, the expression of p-CREB, NR2B, BDNF and p-TrkB was down-regulated, and the apoptosis rate of the hippocampal neurons was increased in S group ( P<0.05). Conclusions:Surgery under propofol anesthesia during mid-pregnancy can decrease the cognitive function of offspring rats, and the mechanism is related to the regulation of HDAC2-CREB-NR2B signaling pathway and the promotion of apoptosis in hippocampal neurons.
ABSTRACT
Objective To evaluate the effects of surgery under ketamine anesthesia during mid-pregnancy on cognitive function of offspring rats.Methods Thirty healthy pregnant Sprague-Dawley rats at14 days of gestation,aged 9-10 weeks,weighing 270-310 g,were assigned to 3 groups (n=10 each)using a random number table method:exploratory laparotomy under ketamine anesthesia group (KSgroup),ketamine anesthesia group (K group) and control group (C group).In KS group,ketamine 20mg/kg was injected via the caudal vein,and then ketamine was continuously infused at a rate of 130mg · kg-1 · h-1 after loss of right reflex to maintain anesthesia for 2 h,and exploratory laparotomy was per-formed after anesthesia was stable.Group K received no exploratory laparotomy and the other treatmentswere similar to those previously described in group KS.The equal volume of normal saline was given insteadin group C.The cliff avoidance,passive avoidance,and Morris water maze tests were used to evaluate the spatial perception and learning and memory ability of the offspring rats on postnatal days 7,23 and 30.Hippocampal tissues of rat offsprings were obtained at 24 h after the end of Morris water maze test to determine neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9) and postsynaptic density 95 (PSD-95) protein and mRNA expression by quantitative polymerase chain reaction or Western blot.Results Compared with group C,the score of cliff avoidance was significantly decreased,the results of Morris water maze test showed that the escape latency was significantly prolonged,the platform-crossing times were decreased,the time spent in the second quadrant was shortened,the expression of NEDD9 and PSD-95 was down-regulated (P ＜ 0.05),and no significant changes were found in the expression of NEDD9 and PSD-95 mRNA in KS group,and no significant changes were found in the indexes mentioned above in K group (P＞0.05).There was no significant difference in the numberof errors in passive avoidance test among the three groups (P＞0.05).Conclusion Ketamine anesthesia during mid-pregnancy exerts no effect on the cognitive function of offspring rats,abdominal surgery under ketamine anesthesia impairs the spatial perception and learning and memory ability of offspring rats,and the mechanism is related to down-regulating the expression of NEDD9 and PSD-95 in hippocampi of offspring rats.