Multiple exposures to sevoflurane across postnatal development may cause cognitive deficits in older age

Zhong, Yuanping; Zhang, Chao; Wang, Yi; Tang, C. N.; Ren, Jun; Wang, Mengmeng; Liu, Dexing

doi:10.1038/s41390-022-01943-x

Cited by 2 publications

(1 citation statement)

References 25 publications

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“…Jiang et al reported that sevoflurane treatment on PND 7, 14, and 21 significantly reduced the hippocampal volume in adult mice on PND 97 [ 59 ]. Moreover, Zhong et al found that repeated sevoflurane exposures during postnatal development caused Multiple exposures to sevoflurane across postnatal development may cause cognitive deficits and increased the levels of tau, p-tau, and Aβ in the hippocampus at 18 months [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Complement C1q-mediated microglial synaptic elimination by enhancing desialylation underlies sevoflurane-induced developmental neurotoxicity

Wang,

Liu,

Meng

et al. 2024

Cell Biosci

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Background Repeated neonatal sevoflurane exposures led to neurocognitive disorders in young mice. We aimed to assess the role of microglia and complement C1q in sevoflurane-induced neurotoxicity and explore the underlying mechanisms. Methods Neonatal mice were treated with sevoflurane on postnatal days 6, 8, and 10, and the Morris water maze was performed to assess cognitive functions. For mechanistic explorations, mice were treated with minocycline, C1q-antibody ANX005, and sialidase-inhibitor N-acetyl-2,3-dehydro-2-deoxyneuraminic acid (NADNA) before sevoflurane exposures. Western blotting, RT-qPCR, Golgi staining, 3D reconstruction and engulfment analysis, immunofluorescence, and microglial morphology analysis were performed. In vitro experiments were conducted in microglial cell line BV2 cells. Results Repeated neonatal sevoflurane exposures resulted in deficiencies in learning and cognition of young mice, accompanied by microglial activation and synapse loss. Sevoflurane enhanced microglia-mediated synapse elimination through C1q binding to synapses. Inhibition of microglial activation and phagocytosis with minocycline significantly reduced the loss of synapses. We further revealed the involvement of neuronal sialic acids in this process. The enhanced activity of sialidase by sevoflurane led to the loss of sialic acids, which facilitated C1q binding to synapses. Inhibition of C1q with ANX005 or inhibition of sialidase with NADNA significantly rescued microglia-mediated synapse loss and improved neurocognitive function. Sevoflurane enhanced the engulfment of BV2 cells, which was reversed by ANX005. Conclusions Our findings demonstrated that C1q-mediated microglial synaptic elimination by enhancing desialylation contributed to sevoflurane-induced developmental neurotoxicity. Inhibition of C1q or sialidase may be a potential therapeutic strategy for this neurotoxicity.

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Section: Discussionmentioning

confidence: 99%

Complement C1q-mediated microglial synaptic elimination by enhancing desialylation underlies sevoflurane-induced developmental neurotoxicity

Wang,

Liu,

Meng

et al. 2024

Cell Biosci

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Role of TREM1 in the sevoflurane‐induced inflammatory activation of microglia in vitro

Tang,

Zhu,

Liu

et al. 2024

Ibrain

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Perioperative neurocognitive disorders (PNDs) are one of the most common complications in perioperative patients, and neuroinflammatory reaction mediated by microglia plays a key role in their formation, but the underlying mechanism remains unknown. Given that the triggering receptor expressed on myeloid cells 1 (TREM1) is a key regulator of inflammation, this study aimed to observe the role of TREM1 on the sevoflurane‐induced inflammatory activation in microglia. BV2 microglia were subjected to varying sevoflurane concentrations and durations to assess their viability using CCK8 and the expression of TREM1, iNOS, and ARG using enzyme‐linked immunosorbent assays. Additionally, TREM1 knockdown lentivirus was employed to examine its impacts on microglia response to sevoflurane and altered expression of inflammatory markers, IL‐1β, TNF‐α, TGF‐β, IL‐10, iNOS, and ARG, as detected using qRT‐PCR and immunofluorescence for INOS/Iba‐1 and ARG/Iba‐1. Our findings underscore the potent inflammatory activation induced by prolonged, high‐concentration sevoflurane exposure on microglia. We highlight the potential role of TREM1 as a modulator of microglial polarization and a potential target for the treatment and prevention of sevoflurane‐induced PNDs.

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Multiple exposures to sevoflurane across postnatal development may cause cognitive deficits in older age

Cited by 2 publications

References 25 publications

Complement C1q-mediated microglial synaptic elimination by enhancing desialylation underlies sevoflurane-induced developmental neurotoxicity

Complement C1q-mediated microglial synaptic elimination by enhancing desialylation underlies sevoflurane-induced developmental neurotoxicity

Role of TREM1 in the sevoflurane‐induced inflammatory activation of microglia in vitro

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