High-concentration sevoflurane exposure in mid-gestation induces apoptosis of neural stem cells in rat offspring

作     者：Yuan Wang Shao-Wei Yin Nan Zhang Ping Zhao 

作者机构：Department of AnesthesiologyShengjing Hospital of China Medical University Department of ObstetricsShengjing Hospital of China Medical University Department of Neuroendocrine PharmacologySchool of PharmacyChina Medical University 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2018年第13卷第9期

页      面：1575-1584页

核心收录：

学科分类：1002[医学-临床医学] 100217[医学-麻醉学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China,No.81671311(to PZ),No.81503273(to NZ) the Science and Technology Foundation of Liaoning Province of China,No.2015020467(to PZ) the Outstanding Scientific Fund of Shengjing Hospital of China Medical University,No.201708 

主　　题：nerve regeneration sevoflurane neural stem cells apoptosis vascular endothelial growth factor PI3K p-AKT anesthesia learning memory developmental neurobiology neural regeneration 

摘      要：Sevoflurane is the most commonly used volatile anesthetic during *** viability of neural stem cells directly affects the development of the ***,it is unknown whether the use of sevoflurane during the second trimester affects the survival of fetal neural stem ***,in this study,we investigated whether exposure to sevoflurane in mid-gestation induces apoptosis of neural stem cells and behavioral *** gestational day 14,pregnant rats were anesthetized with 2% or 3.5% sevoflurane for 2 *** offspring were weaned at 28 days and subjected to the Morris water maze *** brains were harvested to examine neural stem cell apoptosis by immunofluorescence and to measure Nestin and SOX-2 levels by western blot assay at 6,24 and 48 hours after anesthesia as well as on postnatal day（P） 0,14 and *** endothelial growth factor（VEGF） and phosphoinositide 3-kinase（PI3 K）/AKT pathway protein levels in fetal brain at 6 hours after anesthesia were assessed by western blot *** to high-concentration（3.5%） sevoflurane during mid-gestation increased escape latency and path length to the platform,and it reduced the average duration spent in the target quadrant and platform crossing *** 6,24 and 48 hours after anesthesia and at P0,P14 and P28,the percentage of Nestin/terminal deoxynucleotidyl transferase d UTP nick end labeling（TUNEL）-positive cells was increased,but Nestin and SOX-2 protein levels were decreased in the hippocampus of the *** 6 hours after anesthesia,VEGF,PI3 K and phospho-AKT（p-AKT） levels were decreased in the fetal *** changes were not observed in animals given low-concentration（2%） sevoflurane ***,our findings indicate that exposure to a high concentration of sevoflurane（3.5%） in mid-gestation decreases VEGF,PI3 K and p-AKT protein levels and induces neural stem cell apoptosis,thereby causing learning and memory dysfunction in the offspring.