Zhang M Q, Ji M H, Zhao Q S, Jia M, Qiu L L, Yang J J, Peng Y G, Yang J J, Martynyuk A E
Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China Jiangsu Province Key Laboratory of Anaesthesiology, Xuzhou Medical College, Xuzhou, China Jiangsu Province Key Laboratory of Anaesthesia and Analgesia Application Technology, Xuzhou, China.
Br J Anaesth. 2015 Nov;115(5):752-60. doi: 10.1093/bja/aev339.
We tested the hypothesis that developmental effects of repeated neonatal exposure to sevoflurane in rats are exacerbated by stressful experiences received later in life.
Sprague-Dawley male rats received sequential exposures to 3% sevoflurane for two h on postnatal days (P) six, seven, and eight. After weaning at P21, rats were housed either in pairs in an enriched environment (EE) or singly in an enrichment-deprived environment (an adverse environment, AE). The hippocampal concentrations of brain-derived neurotrophic factor (BDNF), and synaptic markers were assessed at P8 and P53. The dentate gyrus neural progenitor proliferation was evaluated at P11 and P53 after administration of bromodeoyuridine (BrdU) at P8 to P10 and at P22 to P27, respectively. Neurobehavioural evaluations were performed at P49 to P53.
Repeated sevoflurane exposure acutely reduced concentrations of BDNF, synaptic markers and neural progenitor proliferation. The sevoflurane group housed in the AE conditions (sevoflurane+AE) had decreased concentrations of BDNF and synaptic markers, and survival of new granule cells and impaired cognitive function compared with the control+AE, control+EE, and sevoflurane+EE groups. The neurobehavioural parameters in the sevoflurane+EE and control+EE groups were similar.
Neurocognitive abnormalities induced by repeated neonatal exposure to sevoflurane can be aggravated by stressful conditions such as social isolation and enrichment deprivation.
我们检验了这样一种假设，即大鼠出生后反复暴露于七氟醚的发育影响会因生命后期经历的应激事件而加剧。
将斯普拉格-道利雄性大鼠在出生后第6、7和8天连续暴露于3%七氟醚中2小时。在出生后第21天断奶后，将大鼠成对饲养在丰富环境（EE）中，或单独饲养在缺乏丰富刺激的环境（不良环境，AE）中。在出生后第8天和第53天评估海马中脑源性神经营养因子（BDNF）的浓度和突触标记物。分别在出生后第8至10天和第22至27天给予溴脱氧尿苷（BrdU）后，在出生后第11天和第53天评估齿状回神经祖细胞增殖。在出生后第49至53天进行神经行为评估。
反复暴露于七氟醚会急性降低BDNF、突触标记物的浓度以及神经祖细胞增殖。与对照组+AE、对照组+EE和七氟醚+EE组相比，饲养在AE条件下的七氟醚组（七氟醚+AE）BDNF和突触标记物浓度降低，新颗粒细胞存活率降低，认知功能受损。七氟醚+EE组和对照组+EE组的神经行为参数相似。
出生后反复暴露于七氟醚所致的神经认知异常可因社会隔离和丰富刺激剥夺等应激条件而加重。
