Sevoflurane anesthesia induces neither contextual fear memory impairment nor alterations in local population connectivity of medial prefrontal cortex local field potentials networks in aged rats

Xu, Xinyu; Zhang, Qian; Tian, Xin; Wang, Guolin

doi:10.1111/fcp.12194

Cited by 3 publications

(3 citation statements)

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“…Exposure to anesthesia in the absence of a surgical stress does not reliably impair cognition when younger animals are utilized [72]. When aged animals are employed, there has been conflicting evidence assessing whether anesthesia exposure can lead to cognitive impairment [73–76]. The variability in results is likely impacted by heterogeneity in study design, including choice of animal models, age of animals, choice of anesthesia agent, dose, duration of exposure, and the choice of cognitive test and timing of assessment relative to anesthesia exposure.…”

Section: Main Bodymentioning

confidence: 99%

Anesthesiology and cognitive impairment: a narrative review of current clinical literature

2019

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Background: The impact of general anesthesia on cognitive impairment is controversial and complex. A large body of evidence supports the association between exposure to surgery under general anesthesia and development of delayed neurocognitive recovery in a subset of patients. Existing literature continues to debate whether these short-term effects on cognition can be attributed to anesthetic agents themselves, or whether other variables are causative of the observed changes in cognition. Furthermore, there is conflicting data on the relationship between anesthesia exposure and the development of long-term neurocognitive disorders, or development of incident dementia in the patient population with normal preoperative cognitive function. Patients with pre-existing cognitive impairment present a unique set of anesthetic considerations, including potential medication interactions, challenges with cooperation during assessment and non-general anesthesia techniques, and the possibility that pre-existing cognitive impairment may impart a susceptibility to further cognitive dysfunction. Main body: This review highlights landmark and recent studies in the field, and explores potential mechanisms involved in perioperative cognitive disorders (also known as postoperative cognitive dysfunction, POCD). Specifically, we will review clinical and preclinical evidence which implicates alterations to tau protein, inflammation, calcium dysregulation, and mitochondrial dysfunction. As our population ages and the prevalence of Alzheimer's disease and other forms of dementia continues to increase, we require a greater understanding of potential modifiable factors that impact perioperative cognitive impairment. Conclusions: Future research should aim to further characterize the associated risk factors and determine whether certain anesthetic approaches or other interventions may lower the potential risk which may be conferred by anesthesia and/or surgery in susceptible individuals.

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Section: Main Bodymentioning

confidence: 99%

Anesthesiology and cognitive impairment: a narrative review of current clinical literature

2019

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“…Sevoflurane is a colorless and volatile liquid anesthetic with a peculiar smell that is used to maintain clinical general anesthesia ( Lu et al, 2010 ; Jiang et al, 2017 ; Yukina et al, 2019 ). Although sevoflurane has numerous advantages, such as universal applicability and safety over other anesthetics, several studies have demonstrated that sevoflurane administration can cause cognitive impairment including postoperative cognitive dysfunction (POCD) and AD ( Lu et al, 2010 ; Xu et al, 2016 ). Certain inhaled anesthetics have been reported to enhance the formation of Aβ plaques and neurofibrillary tangles in animal models ( Xie et al, 2006 ; Ikeda et al, 2007 ; Planel et al, 2007 ; Bianchi et al, 2008 ; Zheng et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Sevoflurane Aggravates the Progress of Alzheimer’s Disease Through NLRP3/Caspase-1/Gasdermin D Pathway

Tian

Xing

Gao

et al. 2022

Front. Cell Dev. Biol.

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Background: Alzheimer’s disease (AD) is the most common form of dementia worldwide. Previous studies have reported that sevoflurane, a frequently used anesthetic, can induce cognitive impairment in preclinical and clinical settings. However, the mechanism underlying the development of this neurotoxicity is currently unclear.Methods: Seven-month-old APP/PS1 mice were placed in an anesthesia induction box containing 3% sevoflurane in 100% O2 for 6 h, while BV2 cells were cultured with 4% sevoflurane for 6 h. Pyroptosis and tau protein expression in excised hippocampus tissues and cells were measured using Western blotting and immunofluorescence assay. Caspase-1 and NLRP3 were knocked out in BV2 microglia using CRISPR/Cas9 technology to determine whether they mediate the effects induced by sevoflurane.Results: Sevoflurane directly activated caspase-1 to induce pyroptosis in the mouse model of AD via NLRP3 and AIM2 activation. In addition, sevoflurane mediated cleavage of gasdermin D (GSDMD) but not gasdermin E (GSDME), promoted the biosynthesis of downstream interleukin-1β and interleukin-18, and increased β-amyloid (Aβ) deposition and tau phosphorylation. The nontoxic caspase-1 small-molecule inhibitor VX-765 significantly inhibited this activation process in microglia, while NLRP3 deletion suppressed sevoflurane-induced caspase-1 cleavage and subsequently pyroptosis, as well as tau pathology. Furthermore, silencing caspase-1 alleviated the sevoflurane-induced release of IL-1β and IL-18 and inhibited tau-related enzymes in microglia.Conclusion: This study is the first to report that clinical doses of sevoflurane aggravate the progression of AD via the NLRP3/caspase-1/GSDMD axis. Collectively, our findings elucidate the crucial mechanisms of NLRP3/caspase-1 in pyroptosis and tau pathogenesis induced by sevoflurane and suggest that VX-765 could represent a novel therapeutic intervention for treating AD.

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“…An additional study found that levels of AD biomarkers (tau and Aβ) were increased following surgical procedure, but were unaffected by anesthesia exposure alone [29]. Animal studies find that the anesthetic sevoflurane alone has no effect on contextual fear memory or synaptic plasticity/connectivity in the medial pre-frontal cortex, but in combination with a surgical procedure did impair memory and connectivity [38]. Thus, there are abundant studies both in support and in disagreement with this hypothesis with conflicting evidence across human and animal studies of anesthetics and surgery.…”

Section: Postoperative Cognitive Delirium and Alzheimer's Diseasementioning

confidence: 99%

Neuroinflammatory challenges compromise neuronal function in the aging brain: Postoperative cognitive delirium and Alzheimer’s disease

Cortese

Bürger

2017

Behavioural Brain Research

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Alzheimer's disease (AD) is a progressive neurodegenerative disease that targets memory and cognition, and is the most common form of dementia among the elderly. Although AD itself has been extensively studied, very little is known about early-stage preclinical events and/or mechanisms that may underlie AD pathogenesis. Since the majority of AD cases are sporadic in nature, advancing age remains the greatest known risk factor for AD. However, additional environmental and epigenetic factors are thought to accompany increasing age to play a significant role in the pathogenesis of AD. Postoperative cognitive delirium (POD) is a behavioral syndrome that primarily occurs in elderly patients following a surgical procedure or injury and is characterized by disruptions in cognition. Individuals that experience POD are at an increased risk for developing dementia and AD compared to normal aging individuals. One way in which cognitive function is affected in cases of POD is through activation of the inflammatory cascade following surgery or injury. There is compelling evidence that immune challenges (surgery and/or injury) associated with POD trigger the release of pro-inflammatory cytokines into both the periphery and central nervous system. Thus, it is possible that cognitive impairments following an inflammatory episode may lead to more severe forms of dementia and AD pathogenesis. Here we will discuss the inflammation associated with POD, and highlight the advantages of using POD as a model to study inflammation-evoked cognitive impairment. We will explore the possibility that advancing age and immune challenges may provide mechanistic evidence correlating early life POD with AD. We will review and propose neural mechanisms by which cognitive impairments occur in cases of POD, and discuss how POD may augment the onset of AD.

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Sevoflurane anesthesia induces neither contextual fear memory impairment nor alterations in local population connectivity of medial prefrontal cortex local field potentials networks in aged rats

Cited by 3 publications

References 57 publications

Anesthesiology and cognitive impairment: a narrative review of current clinical literature

Anesthesiology and cognitive impairment: a narrative review of current clinical literature

Sevoflurane Aggravates the Progress of Alzheimer’s Disease Through NLRP3/Caspase-1/Gasdermin D Pathway

Neuroinflammatory challenges compromise neuronal function in the aging brain: Postoperative cognitive delirium and Alzheimer’s disease

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