Neonatal Exposure to Sevoflurane in Mice Causes Deficits in Maternal Behavior Later in Adulthood

Takaenoki, Yumiko; Satoh, Yasushi; Araki, Yoshiyuki; Kodama, Mitsuyoshi; Yonamine, Ryuji; Yufune, Shinya; Kazama, Tomiei

doi:10.1097/aln.0000435846.28299.e7

Cited by 42 publications

(19 citation statements)

References 53 publications

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“…Sevoflurane is one of the most widely used inhalation anesthetics for pediatric surgery and cesarean delivery due to rapid inhalational induction, tolerable odor, quick emergence and relative cardiovascular stability for infants and children (21). Although sevoflurane exhibits fewer severe effects on the developing brains of animals compared with isoflurane, which is a structurally similar inhaled anesthetic (22), previous studies have demonstrated that sevoflurane may lead to neuronal apoptosis and behavioral dysfunction (23,24).…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane anesthesia in pregnant rats negatively affects nerve function in offspring potentially via inhibition of the Wnt/β-catenin pathway

Wang

Liu

Xing

et al. 2017

Molecular Medicine Reports

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Due to the rapid development of medical technology used to perform intrauterine procedures during pregnancy, the number of patients receiving fetal surgery under general anesthesia is increasing. The aim of the present study was to determine the effects of anesthetics on the offspring of rats, and to identify the potential mechanisms underlying these effects. On day 14 of pregnancy, Sprague‑Dawley rats were equally divided into the following 3 groups (n=9): Control group (n=3), 3% sevoflurane group (n=3) and 4% sevoflurane group (n=3). Following birth of the offspring, the juvenile rats were assessed using an open‑field test, Morris water maze and a continuous passive avoidance test on different days to determine their learning abilities and memory. Western blot and reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analyses were used to examine the expression of multiple critical factors associated with the proliferation and apoptosis of nerve cells, including Ki67, nestin, B cell leukemia/lymphoma 2 (Bcl-2), BCL2 associated X (Bax) and caspase‑3. Additionally, the level of adenosine triphosphate production among the 3 groups were compared. Furthermore, expression alterations in of glycogen synthase kinase‑3β (GSK‑3β) and β‑catenin were examined. The Morris water maze experiment revealed that an increased concentration of sevoflurane exposure significantly reduced the learning and memory abilities of the juvenile rats when compared with controls. In addition, western blotting and RT-qPCR analyses determined that the protein and mRNA expression levels of Bax, caspase‑3 and GSK‑3β were significantly increased relative to the controls. By contrast, the expression levels of nestin, Ki‑67, Bcl‑2 and β‑catenin were significantly reduced. The results of the present study suggest that exposure of pregnant mice to sevoflurane anesthesia demonstrates a negative effect on the learning and memory abilities of their offspring, and the Wnt/β-catenin signaling pathway may be involved in this process.

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Section: Discussionmentioning

confidence: 99%

Sevoflurane anesthesia in pregnant rats negatively affects nerve function in offspring potentially via inhibition of the Wnt/β-catenin pathway

Wang

Liu

Xing

et al. 2017

Molecular Medicine Reports

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“…23,27,28,75,76 However, definitive studies that clearly delineate the association between the pediatric use of general anesthetics and sedatives and developmental neurotoxicity are highly desired. in the current study, [ 18 F]-FEPPa was effectively taken up and concentrated into brain ROis in both control and anesthetic-treated monkeys after intravenous injection.…”

Section: Perioperative Medicinementioning

confidence: 99%

In VivoMonitoring of Sevoflurane-induced Adverse Effects in Neonatal Nonhuman Primates Using Small-animal Positron Emission Tomography

et al. 2016

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Background Animals exposed to sevoflurane during development sustain neuronal cell death in their developing brains. In vivo micro-positron emission tomography (PET)/computed tomography imaging has been utilized as a minimally invasive method to detect anesthetic-induced neuronal adverse effects in animal studies. Methods Neonatal rhesus monkeys (postnatal day 5 or 6, 3 to 6 per group) were exposed for 8 h to 2.5% sevoflurane with or without acetyl-l-carnitine (ALC). Control monkeys were exposed to room air with or without ALC. Physiologic status was monitored throughout exposures. Depth of anesthesia was monitored using quantitative electroencephalography. After the exposure, microPET/computed tomography scans using 18F-labeled fluoroethoxybenzyl-N-(4-phenoxypyridin-3-yl) acetamide (FEPPA) were performed repeatedly on day 1, 1 and 3 weeks, and 2 and 6 months after exposure. Results Critical physiologic metrics in neonatal monkeys remained within the normal range during anesthetic exposures. The uptake of [18F]-FEPPA in the frontal and temporal lobes was increased significantly 1 day or 1 week after exposure, respectively. Analyses of microPET images recorded 1 day after exposure showed that sevoflurane exposure increased [18F]-FEPPA uptake in the frontal lobe from 0.927 ± 0.04 to 1.146 ± 0.04, and in the temporal lobe from 0.859 ± 0.05 to 1.046 ± 0.04 (mean ± SE, P < 0.05). Coadministration of ALC effectively blocked the increase in FEPPA uptake. Sevoflurane-induced adverse effects were confirmed by histopathologic evidence as well. Conclusions Sevoflurane-induced general anesthesia during development increases glial activation, which may serve as a surrogate for neurotoxicity in the nonhuman primate brain. ALC is a potential protective agent against some of the adverse effects associated with such exposures.

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“…However, extensive animal model studies have also showed that this anesthetic agent could cause neuronal apoptosis and behavioral dysfunctions [230-232]. …”

Section: Representative Applications Of Shotgun Lipidomics In Biolmentioning

confidence: 99%

Novel advances in shotgun lipidomics for biology and medicine

Wang

Han

et al. 2016

Progress in Lipid Research

219

186

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The field of lipidomics, as coined in 2003, has made profound advances and been rapidly expanded. The mass spectrometry-based strategies of this analytical methodology-oriented research discipline for lipid analysis are largely fallen into three categories: direct infusion-based shotgun lipidomics, liquid chromatography-mass spectrometry-based platforms, and matrix-assisted laser desorption/ionization mass spectrometry-based approaches (particularly in imagining lipid distribution in tissues or cells). This review focuses on shotgun lipidomics. After briefly introducing its fundamentals, the major materials of this article cover its recent advances. These include the novel methods of lipid extraction, novel shotgun lipidomics strategies for identification and quantification of previously hardly accessible lipid classes and molecular species including isomers, and novel tools for processing and interpretation of lipidomics data. Representative applications of advanced shotgun lipidomics for biological and biomedical research are also presented in this review. We believe that with these novel advances in shotgun lipidomics, this approach for lipid analysis should become more comprehensive and high throughput, thereby greatly accelerating the lipidomics field to substantiate the aberrant lipid metabolism, signaling, trafficking, and homeostasis under pathological conditions and their underpinning biochemical mechanisms.

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Neonatal Exposure to Sevoflurane in Mice Causes Deficits in Maternal Behavior Later in Adulthood

Abstract: In an animal model, sevoflurane exposure in the developing brain caused serious impairment of maternal behaviors when fostering their pups, suggesting pervasive impairment of brain functions including innate behavior essential to species survival.

Cited by 42 publications

References 53 publications

Sevoflurane anesthesia in pregnant rats negatively affects nerve function in offspring potentially via inhibition of the Wnt/β-catenin pathway

Sevoflurane anesthesia in pregnant rats negatively affects nerve function in offspring potentially via inhibition of the Wnt/β-catenin pathway

In VivoMonitoring of Sevoflurane-induced Adverse Effects in Neonatal Nonhuman Primates Using Small-animal Positron Emission Tomography

Novel advances in shotgun lipidomics for biology and medicine

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