The effect and possible mechanism of sevoflurane exposure on electroencephalographic seizures and long-term cognitive function in neonatal rats

中华行为医学与脑科学杂志 Pub Date : 2020-03-20 DOI:10.3760/CMA.J.CN371468-20190921-00661

Jie Wang, Baofeng Yang, Zheng Yang, Ningtao Li, Mingyang Sun, Jiaqiang Zhang

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Abstract

Objective To investigate the effect of sevoflurane anesthesia on electroencephalographic (EEG) seizures and long-term behavior and possible mechanism in neonatal rats. Methods A total of 141 postnatal days 4-6 Sprague-Dawley rats (66 male, 75 female) were divided into 3 groups (n=47 in each group) according to random number table method: control group, sevoflurane group, and NKCC1 inhibitor group, with 22 males and 25 females in each group. Rats in the control group were fed in normal cage without anesthesia; rats in the sevoflurane group were anesthetized with 2.1% sevoflurane for 6 hours; rats in the NKCC1 blocker group received intraperitoneal injection of 1.82 mg / kg bumetanide 30 minutes before anesthesia with 2.1% sevoflurane. The rats in the control group and sevoflurane group were injected subcutaneously with the same dose of DMSO at the same time when the NKCC1 blocker group received the drug intervention, so as to eliminate the influence caused by the solvent. The rats were observed for 30 minutes after recovery from anesthesia and then continued to breastfeed normally. Some of the new born rats received EEG monitoring from 9 to 11 days after being raised; the other rats received EPM and PPI respectively at 60 and 70 days after being raised. Results The results of EEG showed that, compared with the control group, the number of epileptic waves((0.429±0.787), (1.571±0.787), t=2.753, P 0.05). Compared with male rats, the average duration of female rats in sevoflurane group decreased ((6.392±3.374), (2.515±2.992), t=3.044, P 0.05). Comparison between male and female rats: compared with male rats in sevoflurane group, the female rats in sevoflurane group had a longer open arm stay time in EPM experiment (P<0.05), the difference was statistically significant. Conclusion Sevoflurane anesthesia for 6 hours can significantly increase the generation of epileptic waves in EEG of male newborn rats, and cause behavioral abnormalities in adult male rats, which may be related to NKCC1.And male rats are more vulnerable to the negative effects of sevoflurane anesthesia on brain nerve development. Key words: Sevoflurane; Neonatal anesthesia; Bumetanide; Gender; Electroencephalo-graphic; Behaviour; Rat

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七氟醚暴露对新生大鼠脑电图发作和长期认知功能的影响及其可能机制

目的探讨七氟醚麻醉对新生大鼠脑电图（EEG）发作及长期行为的影响及其可能机制。方法采用随机数表法将141只出生后第4～6天的Sprague-Dawley大鼠（雄性66只，雌性75只）分为3组（每组47只）：对照组、七氟醚组和NKCC1抑制剂组，每组雄性22只，雌性25只。对照组大鼠在不麻醉的情况下在正常笼中饲养；七氟醚组大鼠用2.1%七氟醚麻醉6小时；NKCC1阻断剂组大鼠在用2.1%七氟醚麻醉前30分钟腹膜内注射1.82mg/kg布美他奈。对照组和七氟醚组大鼠在NKCC1阻断剂组接受药物干预的同时皮下注射相同剂量的DMSO，以消除溶剂引起的影响。麻醉恢复后观察大鼠30分钟，然后继续正常母乳喂养。一些新生大鼠在饲养后9-11天接受脑电图监测；其他大鼠分别在饲养后60天和70天接受EPM和PPI。结果脑电图结果显示，与对照组相比，癫痫波数（（0.429±0.787），（1.571±0.787，七氟醚组雌性大鼠在EPM实验中张开臂停留时间较长（P<0.05），差异有统计学意义。结论七氟醚麻醉6h可显著增加雄性新生大鼠脑电图中癫痫波的产生，并导致成年雄性大鼠行为异常，这可能与NKCC1有关。而且雄性大鼠更容易受到七氟醚麻醉对脑神经发育的负面影响。关键词：七氟烷；新生儿麻醉；布美他奈；性别；脑电图；行为；大鼠

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中华行为医学与脑科学杂志

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期刊介绍： "Chinese Journal of Behavioral Medicine and Brain Science" (CN 37-1468/R, ISSN 1674-6554) is a national academic journal under the supervision of the National Health Commission, sponsored by the Chinese Medical Association and Jining Medical College. The journal was founded in June 1992 and was formerly known as "Chinese Journal of Behavioral Medicine" (1992-1993) and "Chinese Behavioral Medical Science" (1994-2008). In 2009, it was renamed "Chinese Journal of Behavioral Medicine and Brain Science" with the approval of the State Administration of Press, Publication, Radio, Film and Television. The purpose of "Chinese Journal of Behavioral Medicine and Brain Science" is to implement the health and health policies of the Party and the State, implement the principle of combining theory with practice and popularization and improvement, and reflect the major progress in the theory and practical application of behavioral medicine and brain science in my country. It publishes academic papers and scientific research results in the field of behavioral medicine and brain science in my country, and has columns such as monographs/reviews, basic research, clinical research, health prevention, methods and techniques, psychological behavior and evaluation, and systematic evaluation.