Sevoflurane Post-Conditioning Ameliorates Neuronal Deficits and Axon Demyelination After Neonatal Hypoxic Ischemic Brain Injury: Role of Microglia/Macrophage

Xue, Hang; Zhang, Yahan; Gao, Qiushi; Wu, Ziyi; Niu, Jiayuan; Li, Chang; Zhao, Ping

doi:10.1007/s10571-020-00949-5

Cited by 13 publications

(11 citation statements)

References 27 publications

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“…In addition, melatonin pretreatment also restored the amplitude of AMPA receptor-mediated EPSCs to a level even similar to normal control (Figure 2K,L). These data indicated that melatonin pretreatment has remarkable long-term Because MT1 receptor was also up-regulated in NG2positive oligodendrocyte precursors and chronic dysmyelination had been reported following Sev treatment, [37][38][39] we next examined whether melatonin could alleviate the toxic effects of Sev on oligodendrocytes. Sev treatment significantly inhibited the expression of PDGFRα, NG2, and Sox10 (markers of oligodendrocyte precursors), Olig2 (marker of cell fate determined oligodendrocyte), and MBP (marker of mature oligodendrocyte) (Figure 3A-F).…”

Section: Melatonin Pretreatment Alleviates the Long-term Toxic Effects Of Repeated Neonatal Sev Exposurementioning

confidence: 98%

Melatonin pretreatment alleviates the long‐term synaptic toxicity and dysmyelination induced by neonatal Sevoflurane exposure via MT1 receptor‐mediated Wnt signaling modulation

Liang

Tian

Zhao

et al. 2021

Journal of Pineal Research

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Sevoflurane (Sev) is one of the most widely used pediatric anesthetics. The major concern of neonatal repeated application of Sev is its potential long-term impairment of cognition and learning/memory, for which there still lacks effective treatment. At the cellular level, Sev exerts toxic effects in multiple aspects, making it difficult for effective interference. Melatonin is a pineal hormone regulated by and feedbacks to biological rhythm at physiological condition. Recent studies have revealed significant neuroprotective effects of exogenous melatonin or its agonists under various pathological conditions. Whether melatonin could prevent the long-term toxicity of Sev remains elusive. Here, we report that neonatal repeated Sev exposure up-regulated MT1 receptor in hippocampal neurons and oligodendrocytes. Pretreatment with melatonin significantly alleviated Sevinduced synaptic deficiency, dysmyelination, and long-term learning impairment. Both MT1-shRNA and MT1 knockout effectively blocked the protective effects of melatonin on synaptic development, myelination, and behavior performance. Interestingly, long-lasting suppression of Wnt signaling, instead of cAMP/PKA signaling, was observed in hippocampal neurons and oligodendrocytes after neonatal Sev exposure. Pharmacologically activating Wnt signaling rescued both the long-term synaptic deficits and dysmyelination induced by Sev.Further analysis showed that MT1 receptor co-expressed well with β-catenin and

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Section: Melatonin Pretreatment Alleviates the Long-term Toxic Effects Of Repeated Neonatal Sev Exposurementioning

confidence: 98%

Melatonin pretreatment alleviates the long‐term synaptic toxicity and dysmyelination induced by neonatal Sevoflurane exposure via MT1 receptor‐mediated Wnt signaling modulation

Liang

Tian

Zhao

et al. 2021

Journal of Pineal Research

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“…The innate immune response is a complex physiological process that occurs around microglia, which plays a key role in the development of some of the main pathological features of AD ( Li et al, 2017 ; Dong et al, 2021 ). Under normal conditions, intracerebral microglia maintain the balance between tau and Aβ deposition and clearance ( Tang et al, 2011 ; Xue et al, 2020 ); and several studies have implicated microglial dysfunction in the pathogenesis of AD ( He et al, 2015 ; Sung et al, 2019 ).…”

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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“…For instance, the study by Hwang et al (2017) showed that sevoflurane postconditioning decreased the production of multiple proinflammatory cytokines such as TNF-α, IL-6, and IL-1β, via the Toll-like receptor-4/NF-κB pathway, which was activated by cerebral ischemia/reperfusion injury. Similarly, Xue et al (2020) reported that sevoflurane postconditioning significantly attenuated the activation of hypoxic-ischemic brain injury-induced microglia/macrophage and impairment of the cognitive function.…”

Section: Discussionmentioning

confidence: 86%

The Mechanisms of Sevoflurane-Induced Neuroinflammation

Huang

Ying

Yang

et al. 2021

Front. Aging Neurosci.

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Sevoflurane is one of the most commonly used inhaled anesthetics due to its low blood gas coefficient, fast onset, low airway irritation, and aromatic smell. However, recent studies have reported that sevoflurane exposure may have deleterious effects on cognitive function. Although neuroinflammation was most widely mentioned among the established mechanisms of sevoflurane-induced cognitive dysfunction, its upstream mechanisms have yet to be illustrated. Thus, we reviewed the relevant literature and discussed the most mentioned mechanisms, including the modulation of the microglial function, blood–brain barrier (BBB) breakdown, changes in gut microbiota, and ease of cholinergic neurotransmission to help us understand the properties of sevoflurane, providing us new perspectives for the prevention of sevoflurane-induced cognitive impairment.

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Sevoflurane Post-Conditioning Ameliorates Neuronal Deficits and Axon Demyelination After Neonatal Hypoxic Ischemic Brain Injury: Role of Microglia/Macrophage

Cited by 13 publications

References 27 publications

Melatonin pretreatment alleviates the long‐term synaptic toxicity and dysmyelination induced by neonatal Sevoflurane exposure via MT1 receptor‐mediated Wnt signaling modulation

Melatonin pretreatment alleviates the long‐term synaptic toxicity and dysmyelination induced by neonatal Sevoflurane exposure via MT1 receptor‐mediated Wnt signaling modulation

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

The Mechanisms of Sevoflurane-Induced Neuroinflammation

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