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Sevoflurane induced neurotoxicity

Sheng Peng, Hong-Zhu Yan, Pei-Rong Liu, Xiao-Wei Shi, Chun-Liang Liu, Qi Liu, Yu Zhang
BACKGROUND/AIMS: Sevoflurane, a commonly used volatile anesthetic, recently has been found has neurotoxicity in the central nervous system of neonatal rodents. This study aimed to reveal whether phosphodiesterase 4 (PDE-4) inhibitor roflumilast has protective functions in sevoflurane-induced nerve damage. METHODS: Hippocampal neurons were isolated from juvenile rats, and were exposed to sevoflurane with or without roflumilast treatment. Cell viability and apoptosis were respectively assessed by CCK-8 and flow cytometry...
March 13, 2018: Cellular Physiology and Biochemistry
Guolin Lu, Huali Xu, Wei Zhao, Jianbo Zhang, Dongdong Rao, Shiyuan Xu
Emerging evidence has shown that long noncoding RNA (lncRNA) plays a crucial role in controlling neural stem cells' (NSCs) survival. However, the fundamental role of lncRNA underlying sevoflurane-induced neurotoxicity remains poorly elucidated. In the present study, we investigate the effect of sevoflurane-induced neurotoxicity in a concentration-dependent and duration-dependent manner. Furthermore, we assayed the differential profile of lncRNA in rat hippocampal NSCs following sevoflurane exposure, and identified lncRNA Gadd45a and the correlation between lncRNA Gadd45a and Gadd45a...
March 8, 2018: Neuroreport
XiaoHong Tang, YiZe Li, JiYing Ao, Ling Ding, Yang Liu, Yuan Yuan, ZhiFen Wang, GuoLin Wang
Detrimental effects of volatile anaesthetics, including sevoflurane, on the structure and function of the developing brain have been reported. The internalization of N-methyl-D-aspartate receptors (NMDARs) contributes to anaesthetic neurotoxicity. Both nicotinic acetylcholine receptors (nAChRs) and NMDAR play a critical role in the development of the nervous system. Moreover, nAChR can interact with NMDAR, and previous studies have demonstrated modulation of NMDAR by nAChR. In our study, we used an α7 nicotinic acetylcholine receptor (α7nAChR) agonist and α7nAChR antagonist to explore the role of α7nAChR and NMDAR in sevoflurane-induced long-term effects on memory and dendritic spine both in vivo and in vitro...
2018: PloS One
Woosuk Chung, Seunghwan Yoon, Yong Sup Shin
Background: Earlier studies have reported conflicting results regarding long-term behavioral consequences after anesthesia during the fetal period. Previous studies also suggest several factors that may explain such conflicting data. Thus, we examined the influence of age and sex on long-term behavioral consequences after multiple sevoflurane exposures during the fetal period. Methods: C57BL/6J pregnant mice received oxygen with or without sevoflurane for 2 hours at gestational day (GD) 14-16...
December 2017: Korean Journal of Anesthesiology
Ruixue Song, Xiaomin Ling, Mengyuan Peng, Zhanggang Xue, Jing Cang, Fang Fang
Maternal sevoflurane exposure during pregnancy is associated with increased risk for behavioral deficits in offspring. Several studies indicated that neurogenesis abnormality may be responsible for the sevoflurane-induced neurotoxicity, but the concrete impact of sevoflurane on fetal brain development remains poorly understood. We aimed to investigate whether maternal sevoflurane exposure caused learning and memory impairment in offspring through inducing abnormal development of the fetal prefrontal cortex (PFC)...
2017: Stem Cells International
Lubin Huang, Kejing Huang, Hong Ning
AIM: As a widely used general anesthetic, sevoflurane has been found to induce cognitive and memory defectsin the elderly. This may increase the risk of Alzheimer's disease. This study explores the neuroprotective effect of hispidulin, a natural flavone compound, against sevoflurane-induced memory dysfunction. METHODS: The effect of sevoflurane exposure on memory function was evaluated by novel object recognition and Y-maze testing using an aged rat model. The apoptotic cell death in the hippocampus of rats was assessed using a TUNEL assay...
October 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Xue Zhou, Dihan Lu, Wen-da Li, Xiao-Hui Chen, Xiao-Yu Yang, Xi Chen, Zhi-Bin Zhou, Jiang-Hong Ye, Xia Feng
Anesthesia-induced neurotoxicity in immature animals has raised concerns about similar effects occurring in young children. Our study investigated two commonly used anesthetics-sevoflurane and propofol-for neurotoxicity in young children. Forty-seven children (aged 12-36 months) undergoing hypospadias repair surgery were randomized to receive sevoflurane (SG, n = 24) or propofol (PG, n = 23) general anesthesia. Venous blood was collected at three different times-immediately after induction, 2 h, and 3 days after surgery...
October 25, 2017: Neurotoxicity Research
P Liang, F Li, J Liu, D Liao, H Huang, C Zhou
Background: In addition to general anaesthetic effects, sevoflurane can also induce hyperactive behaviours during induction and recovery, which may contribute to neurotoxicity; however, the mechanism of such effects is unclear. Volatile anaesthetics including isoflurane have been found to activate the kainate (GluK2) receptor. We developed a novel mouse model and further explored the involvement of kainate (GluK2) receptors in sevoflurane-induced hyperactivity. Methods: Maximal speed, mean speed, total movement distance and resting percentage of C57BL/6 mice were quantitatively measured using behavioural tracking software before and after sevoflurane anaesthesia...
November 1, 2017: British Journal of Anaesthesia
J F Perez-Zoghbi, W Zhu, M R Grafe, A M Brambrink
Background: Exposure of infant animals to clinically used anaesthetics is associated with acute structural brain abnormalities and development functional alterations. The α 2 -adrenoceptor agonist dexmedetomidine (DEX) induces sedation, analgesia, and provides neuroprotection in experimental brain injury models. However, it is unknown whether DEX also affords protection in the developing brain against anaesthesia using sevoflurane (SEVO), which is commonly used in paediatric anaesthesia...
September 1, 2017: British Journal of Anaesthesia
Han Lu, Ning Liufu, Yuanlin Dong, Guanghong Xu, Yiying Zhang, Liqi Shu, Sulpicio G Soriano, Hui Zheng, Buwei Yu, Zhongcong Xie
BACKGROUND: Children with multiple exposures to anesthesia and surgery may have an increased risk of developing cognitive impairment. Sevoflurane, a commonly used anesthetic in children, has been reported to decrease levels of postsynaptic density 95 protein. However, the upstream mechanisms and downstream consequences of the sevoflurane-induced reduction in postsynaptic density 95 protein levels remains largely unknown. We therefore set out to assess whether sevoflurane acts on ubiquitination-proteasome pathway to facilitate postsynaptic density 95 protein degradation...
December 2017: Anesthesiology
Xu Yang, Sun Yang, Chen Hong, Wang Yu, Wang Guonian
General anesthesia in patients with or at risk for neuronal injury remains challenging due to the neurotoxic effects of volatile anesthetics. One inhalation anesthetic, sevoflurane, induces neuronal damage, including neuroapoptosis, and learning and memory impairment. Panax Notoginseng Saponins (PNS) is the active ingredient of Sanqui and has been reported to exert neuroprotective effects. In the current study, the protective effect of PNS on sevoflurane‑induced nerve cell injury was explored. Cell proliferation was significantly reduced in a dose‑dependent manner following stimulation with sevoflurane...
November 2017: Molecular Medicine Reports
He Huang, Cun-Ming Liu, Jie Sun, Wen-Jie Jin, Yu-Qing Wu, Jing Chen
BACKGROUND: Sevoflurane is one of the most widely used inhalation anesthetics in pediatric anesthesia. A large number of studies have demonstrated that repeated treatment with high concentrations or long durations of sevoflurane anesthesia during the neonatal period can induce neuroapoptosis and long-term learning disability. In clinical practice, we observed that a subset of patients underwent minor surgery under sevoflurane anesthesia more than once from birth to adolescence. Therefore, this research was conducted to investigate whether a 2% concentration of sevoflurane (clinically relevant usage of sevoflurane) for 1 h (a short duration) can induce neuroapoptosis and neurocognitive dysfunction in adolescent rats that received sevoflurane (2% for 1 h) during the neonatal period...
November 2017: Der Anaesthesist
Xiang Lv, Jia Yan, Jue Jiang, Xuhui Zhou, Yi Lu, Hong Jiang
Sevoflurane is the most widely used anaesthetic administered by inhalation. Exposure to sevoflurane in neonatal mice can induce learning deficits and abnormal social behaviours. MicroRNA (miR)-27a-3p, a short, non-coding RNA that functions as a tumour suppressor, is up-regulated after inhalation of anaesthetic, and peroxisome proliferator-activated receptor γ (PPAR-γ) is one of its target genes. The objective of this study was to investigate how the miR-27a-3p-PPAR-γ interaction affects sevoflurane-induced neurotoxicity...
November 2017: Journal of Neurochemistry
Si-Ning Xie, Hong Ye, Jun-Fa Li, Li-Xin An
Exposure of neonatal rat to sevoflurane leads to neurodegeneration and deficits of spatial learning and memory in adulthood. However, the underlying mechanisms remain unclear. The type A γ-aminobutyric acid receptor (GABAA R) is a target receptor for sevoflurane. The present study intends to investigate the changes in GABAA R α1/α2 expression and its relationship with the neurotoxicity effect due to sevoflurane in neonatal rats. After a dose-response curve was constructed to determine minimum alveolar concentration (MAC) and safety was guaranteed in our 7-day-old neonatal rat pup mode, we conducted two studies among the following groups: (A) the control group; (B) the sham anesthesia group; and (C) the sevoflurane anesthesia group and all three groups were treated in the same way as the model...
August 26, 2017: Journal of Neuroscience Research
Jialong Jiang, Shasha Li, Yiqiao Wang, Xue Xiao, Yi Jin, Yilong Wang, Zeyong Yang, Shikai Yan, Yuanhai Li
Repeated or prolonged anesthesia to pregnant women disturbs neurodevelopment of developing infants, but its mechanism has not been elaborated absolutely. This study was conducted to investigate the mechanism of potential neurotoxicity on their offspring generation after sevoflurane anesthesia in adult animals during pregnancy based on metabolomics. 16 pregnant rats were equally assigned to sevoflurane group and control group, and serum samples were collected from their 7-day-old offspring for metabolomics analysis using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry...
August 24, 2017: International Journal of Developmental Neuroscience
Maria Fernanda Quiroz-Padilla, Gemma Guillazo-Blanch, Magdy Y Sanchez, Maria Andrea Dominguez-Sanchez, Rosa Margaria Gomez
Different anesthesia methods can variably influence excitotoxic lesion effects on the brain. The main purpose of this review is to identify potential differences in the toxicity to nervous system cells of two common inhalation anesthesia methods, isoflurane and sevoflurane, used in combination with an excitotoxic lesion procedure in rodents. The use of bioassays in animal models has provided the opportunity to examine the role of specific molecules and cellular interactions that underlie important aspects of neurotoxic effects relating to calcium homeostasis and apoptosis activation...
August 17, 2017: Current Pharmaceutical Design
Mei-Li Ding, Hui Ma, Yi-Gang Man, Hong-Yan Lv
Epigallocatechin-3-gallate (EGCG), a polyphenol in green tea, is an effective antioxidant and possesses neuroprotective effects. Brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are crucial for neurogenesis and synaptic plasticity. In this study, we aimed to assess the protective effects of EGCG against sevoflurane-induced neurotoxicity in neonatal mice. Distinct groups of C57BL/6 mice were given EGCG (25, 50, or 75 mg/kg body weight) from postnatal day 3 (P3) to P21 and were subjected to sevoflurane (3%; 6 h) exposure on P7...
July 5, 2017: Canadian Journal of Physiology and Pharmacology
Zhongliang Sun, Maiko Satomoto, Yushi U Adachi, Koshi Makita
BACKGROUND: Neonatal exposure to anesthetics induces neuronal apoptosis and long-term cognitive dysfunction in rodents. We showed that the nicotinamide adenine dinucleotide phosphate-oxidase inhibitor apocynin not only reduces neurotoxicity by decreasing superoxide levels and preventing mitochondrial dysfunction but also improves long-term memory impairment in neonatal mice exposed to sevoflurane. We also found that after the contextual fear conditioning test, glutamatergic neurons expressed c-Fos (neural activation) regardless of previous exposure to sevoflurane...
June 2017: Korean Journal of Anesthesiology
G Xu, H Lu, Y Dong, D Shapoval, S G Soriano, X Liu, Y Zhang, Z Xie
Background: Anaesthesia can induce cognitive deficiency in young rodents and monkeys. Mitochondrial dysfunction contributes to the anaesthesia-induced neurotoxicity and neurobehavioural deficits. We therefore assessed the effects of the mitochondrial energy enhancer coenzyme Q 10 (CoQ 10 ) on anaesthesia-induced cognitive deficiency in young mice to investigate the role of mitochondrial dysfunction. Methods: Young mice ( n =134) were randomly assigned into the following four groups: control plus corn oil vehicle (60% oxygen); 3% sevoflurane [2 h daily on postnatal day (P) 6, 7, and 8] plus vehicle; CoQ 10 (50 mg kg -1 ) plus vehicle; or 3% sevoflurane plus CoQ 10 plus vehicle...
September 1, 2017: British Journal of Anaesthesia
Yafang Liu, Daowei Lin, Chuiliang Liu, Yifan Zhao, Zhiwen Shen, Kun Zhang, Minghui Cao, Yujuan Li
Sevoflurane has been reported to induce neurotoxicity and cognitive impairment in the developing brains. However, the underlying molecular mechanisms remain poorly understood. Recent studies have demonstrated aberrant cyclin-dependent kinase 5 (CDK5) activity is implicated in inhaled anesthetic-induced neurotoxicity. CDK5/CRMP2 signaling is involved in the cortical and hippocampal dendritic development. The aim of present study is to investigate whether the CDK5/CRMP2 pathway mediates sevoflurane-induced dendritic development abnormalities...
April 24, 2017: Neuroscience Letters
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