Mechanistic insight into sevoflurane-associated developmental neurotoxicity

Sun, Menghong; Xie, Zhongcong; Zhang, Jiayang; Leng, Yufang

doi:10.1007/s10565-021-09677-y

Cited by 39 publications

(30 citation statements)

References 140 publications

(162 reference statements)

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“…We also found that when rats were anesthetized with sevo urane at a concentration of 2.32% for 1.5 h, there was no signi cant correlation between the time of recovery of motor coordination and the duration of anesthesia, but anesthesia for less than 1 h resulted in a relatively prolonged period of anesthesia and awakening [9] . And some studies have found that sevo urane anesthesia is toxic to neurons in rodents, but the speci c mechanism is not yet known [10] . Therefore, in this experiment, healthy adult rats were selected to investigate the effects of sevo urane anesthesia at different concentrations and for different times on the blood concentration of free HFIP in the blood of rats and its relationship with the behavior of adult rats during the awakening period of anesthesia.…”

Section: Discussionmentioning

confidence: 99%

Effects of Different Concentrations of Sevoflurane Anaesthesia on Blood Free Hexafluoroisopropanol Levels and Anaesthesia Awakening Period in Adult Rats

Zhang,

He,

Jiang

et al. 2024

Preprint

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Background: Sevoflurane is metabolized in the body to Hexafluoro-isopropanol(HFIP). The aim of this study was to compare the levels of free HFIP in the blood of rats after inhalation of different concentrations of sevoflurane and the effects on the awakening period of rats, and to investigate the related mechanisms. Methods: Seventy-four healthy male rats of 8–10 weeks of age were selected. Six rats were used to determine the blood/gas partition coefficient of HFIP. Forty-eight rats were randomly divided into three groups: 0.5 minimum alveolar concentration (MAC) (group S1), 1.0 MAC (group S2), and 1.5 MAC (group S3), with 16 rats in each group. The free HFIP concentration in blood was measured by gas chromatography. Twenty rats were randomly divided into five groupsof four rats each, anesthetized by inhalation of 1.0 MAC sevoflurane for mine field tests, and immunohistochemistry was used to detect glial changes in cognition-related brain regions of rats. Results: The peak concentration of free HFIP in the blood of rats appeared at an inhalation concentration of 1 MAC (P<0.05), and the total mileage of the mine experiment was the longest in rats anesthetized for 1 h with 1.0 MAC sevoflurane (P<0.05).Expression of glial fibrillary acidic protein (GFAP) and IBA1 in cognitively related brain regions was significantly higher in rats anesthetized for 1 h with 1.0 MAC sevoflurane than the other time points (P<0.05). Conclusions: Free HFIP in the blood of rats reached its peak 1 hour after 1.0 MAC sevoflurane anesthesia was inhaled. Rats showed obvious arousal and excitement at this time, and glial cells and inflammatory factors in cognitively related brain regions were significantly activated.

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Section: Discussionmentioning

confidence: 99%

Effects of Different Concentrations of Sevoflurane Anaesthesia on Blood Free Hexafluoroisopropanol Levels and Anaesthesia Awakening Period in Adult Rats

Zhang,

He,

Jiang

et al. 2024

Preprint

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“…As with other anesthetics, the potential mechanisms by which sevoflurane causes neurotoxicity are controversial. A recent review specifically summarized its possible mechanisms, including nerve cell damage and death, tau protein phosphorylation, and neuroendocrine abnormalities ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

A bibliometric analysis of the neurotoxicity of anesthesia in the developing brain from 2002 to 2021

et al. 2023

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BackgroundThe neurotoxicity effects of anesthetic exposure on the developing brain have been one of the current research hotspots and numerous articles were published in the past decades. However, the quality and comparative information of these articles have not been reported. This research aimed to provide a comprehensive overview of the current state of the field by investigating research hotspots and publication trends concerning the neurotoxicity of anesthesia in the developing brain.Materials and methodsOn 15 June 2022, we searched articles on the neurotoxicity of anesthesia in the developing brain through the Science Citation Index databases from 2002 to 2021. Data of the author, title, publication, funding agency, date of publication, abstract, type of literature, country, journal, keywords, number of citations, and research direction were collected for further analysis.ResultsWe searched and analyzed 414 articles in English on the field of neurotoxicity of anesthesia in the developing brain from 2002 to 2021. The country with the largest number of publications was The United States (US) (n = 226), which also had the largest total number of citations (10,419). Research in this field reached a small peak in 2017. Furthermore, the largest number of articles were published in three journals, Anesthesiology, Anesthesia and Analgesia, and Pediatric Anesthesia. The top 20 articles that were cited most often were studied. In addition, the top hotspots of this area in clinical investigations and basic research were analyzed separately.ConclusionThis study provided an overview of the development in the neurotoxicity of anesthesia in the developing brain using bibliometric analysis. Current clinical studies in this area were mainly retrospective; in the future, we should place more emphasis on prospective, multicenter, long-term monitoring clinical studies. More basic research was also needed on the mechanisms of neurotoxicity of anesthesia in the developing brain.

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“…Since this discovery, preclinical investigations on how anesthetics affect the developing brain have grown significantly ( Lin et al, 2017 ; Jevtovic-Todorovic, 2018 ). For example, sevoflurane exposure at critical stages of development may result in neuronal apoptosis and cognitive impairments, according to experimental research on animals ( Sun et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Role of posttranslational modifications in memory and cognitive impairments caused by neonatal sevoflurane exposure

Jiang

Zhou²,

Tan³

et al. 2023

Front. Pharmacol.

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With the advancement of technology, increasingly many newborns are receiving general anesthesia at a young age for surgery, other interventions, or clinical assessment. Anesthetics cause neurotoxicity and apoptosis of nerve cells, leading to memory and cognitive impairments. The most frequently used anesthetic in infants is sevoflurane; however, it has the potential to be neurotoxic. A single, short bout of sevoflurane exposure has little impact on cognitive function, but prolonged or recurrent exposure to general anesthetics can impair memory and cognitive function. However, the mechanisms underlying this association remain unknown. Posttranslational modifications (PTMs), which can be described roughly as the regulation of gene expression, protein activity, and protein function, have sparked enormous interest in neuroscience. Posttranslational modifications are a critical mechanism mediating anesthesia-induced long-term modifications in gene transcription and protein functional deficits in memory and cognition in children, according to a growing body of studies in recent years. Based on these recent findings, our paper reviews the effects of sevoflurane on memory loss and cognitive impairment, discusses how posttranslational modifications mechanisms can contribute to sevoflurane-induced neurotoxicity, and provides new insights into the prevention of sevoflurane-induced memory and cognitive impairments.

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Mechanistic insight into sevoflurane-associated developmental neurotoxicity

Cited by 39 publications

References 140 publications

Effects of Different Concentrations of Sevoflurane Anaesthesia on Blood Free Hexafluoroisopropanol Levels and Anaesthesia Awakening Period in Adult Rats

Effects of Different Concentrations of Sevoflurane Anaesthesia on Blood Free Hexafluoroisopropanol Levels and Anaesthesia Awakening Period in Adult Rats

A bibliometric analysis of the neurotoxicity of anesthesia in the developing brain from 2002 to 2021

Role of posttranslational modifications in memory and cognitive impairments caused by neonatal sevoflurane exposure

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