Top

Published in:

21-12-2023 | Sevoflurane | Research Article

SESN2 attenuates sevoflurane-induced cognitive impairment and neuroinflammation in rats

Authors: Li Sun, Yangyang Li, Daliang Wang, Xiaoya Hong

Published in: Experimental Brain Research | Issue 2/2024

Abstract

Long-term use of sevoflurane, an inhalation anesthetic, could negatively impact cognitive function. Current studies have suggested that cognitive impairment induced by sevoflurane may be associated with neuroinflammation. Sestrin2 (SESN2), which belongs to a family of stress-inducible genes, has been reported to exert neuroprotective effects against brain injury. However, its role and underlying mechanisms in sevoflurane-induced cognitive dysfunction in aged rats remain unknown. A sevoflurane-induced aging rat injury model with or without SESN2 overexpression was constructed. The learning and memory abilities of rats were evaluated by the MWM test. ELISA assay and qRT-PCR were conducted to analyze the level of pro-inflammatory factors in the hippocampus. Levels of oxidative stress markers were measured by DHE staining or kit methods. Neuronal apoptosis in the hippocampus was detected using TUNEL assay. Expression of proteins were analyzed by western blot. Sevoflurane exposure caused elevated protein level of SESN2 in hippocampus and cognitive impairment of aged rats. Importantly, overexpression of SESN2 alleviated sevoflurane-induced cognitive dysfunction and inhibited the production of pro-inflammatory factors, oxidative stress, and neuronal apoptosis in the hippocampus. Furthermore, SESN2 overexpression suppressed NLRP3 inflammasome activation induced by sevoflurane. These findings suggested that SESN2 could exert neuroprotective against sevoflurane-induced nerve injury of aged rats through anti-oxidant and anti-inflammatory effects.

Coll RC, Schroder K, Pelegrín P (2022) NLRP3 and pyroptosis blockers for treating inflammatory diseases. Trends Pharmacol Sci 43:653–668. https://doi.org/10.1016/j.tips.2022.04.003CrossRefPubMed

Dong P, Zhao J, Li N, Lu L, Li L, Zhang X, Li D (2018) Sevoflurane exaggerates cognitive decline in a rat model of chronic intermittent hypoxia by aggravating microglia-mediated neuroinflammation via downregulation of PPAR-γ in the hippocampus. Behav Brain Res 347:325–331. https://doi.org/10.1016/j.bbr.2018.03.031CrossRefPubMed

Han D, Kim H, Kim S, Le QA, Han SY, Bae J, Park HW (2022) Sestrin2 protects against cholestatic liver injury by inhibiting endoplasmic reticulum stress and NLRP3 inflammasome-mediated pyroptosis. Exp Mol Med 54:239–251. https://doi.org/10.1038/s12276-022-00737-9CrossRefPubMedPubMedCentral

Kantonen O, Laaksonen L, Alkire M, Scheinin A, Långsjö J, Kallionpää R, Scheinin H (2023) Decreased thalamic activity is a correlate for disconnectedness during anesthesia with propofol, dexmedetomidine and sevoflurane but not S-Ketamine. J Neurosci. https://doi.org/10.1523/jneurosci.2339-22.2023CrossRefPubMedPubMedCentral

Kelley N, Jeltema D, Duan Y, He Y (2019) The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci. https://doi.org/10.3390/ijms20133328CrossRefPubMedPubMedCentral

Kim MJ, Bae SH, Ryu JC, Kwon Y, Oh JH, Kwon J, Yoon JH (2016) SESN2/sestrin2 suppresses sepsis by inducing mitophagy and inhibiting NLRP3 activation in macrophages. Autophagy 12:1272–1291. https://doi.org/10.1080/15548627.2016.1183081CrossRefPubMedPubMedCentral

Kuzminskaite V, Kontrimaviciute E, Kauzonas E, Slauzgalvyte I, Bukelyte G, Bruzyte-Narkiene G, Jatuzis D (2023) Sevoflurane and desflurane effects on early cognitive function after low-risk surgery: a randomized clinical trial. Brain and Behavior 13:e3017. https://doi.org/10.1002/brb3.3017CrossRefPubMedPubMedCentral

Li L, Xiao L, Hou Y, He Q, Zhu J, Li Y, Zhao Y (2016) Sestrin2 silencing exacerbates cerebral ischemia/reperfusion injury by decreasing mitochondrial biogenesis through the AMPK/PGC-1α pathway in rats. Sci Rep 6:30272. https://doi.org/10.1038/srep30272CrossRefPubMedPubMedCentral

Li R, Huang Y, Semple I, Kim M, Zhang Z, Lee JH (2019) Cardioprotective roles of sestrin 1 and sestrin 2 against doxorubicin cardiotoxicity. Am J Physiol Heart Circ Physiol 317:H39-h48. https://doi.org/10.1152/ajpheart.00008.2019CrossRefPubMedPubMedCentral

Liu J, Li Y, Mei C, Ning X, Pang J, Gu L, Wu L (2020) Phytic acid exerts protective effects in cerebral ischemia-reperfusion injury by activating the anti-oxidative protein sestrin2. Biosci Biotechnol Biochem 84:1401–1408. https://doi.org/10.1080/09168451.2020.1754158CrossRefPubMed

Liu X, Li M, Zhu J, Huang W, Song J (2021) Sestrin2 protects against traumatic brain injury by reinforcing the activation of Nrf2 signaling. Hum Exp Toxicol 40:1095–1111. https://doi.org/10.1177/0960327120984224CrossRefPubMed

Luo L, Wu J, Qiao L, Lu G, Li J, Li D (2020) Sestrin 2 attenuates sepsis-associated encephalopathy through the promotion of autophagy in hippocampal neurons. J Cell Mol Med 24:6634–6643. https://doi.org/10.1111/jcmm.15313CrossRefPubMedPubMedCentral

Netto MB, de Oliveira JAN, Goldim M, Mathias K, Fileti ME, da Rosa N, Petronilho F (2018) Oxidative stress and mitochondrial dysfunction contributes to postoperative cognitive dysfunction in elderly rats. Brain Behav Immun 73:661–669. https://doi.org/10.1016/j.bbi.2018.07.016CrossRefPubMed

Peng S, Li P, Liu P, Yan H, Wang J, Lu W, Zhou Y (2020) Cistanches alleviates sevoflurane-induced cognitive dysfunction by regulating PPAR-γ-dependent antioxidant and anti-inflammatory in rats. J Cell Mol Med 24:1345–1359. https://doi.org/10.1111/jcmm.14807CrossRefPubMed

Qiu J, Zhang Y, Xie M (2021) Chrysotoxine attenuates sevoflurane-induced neurotoxicity in vitro via regulating PI3K/AKT/GSK pathway. Signa Vitae 17:185–191. https://doi.org/10.22514/sv.2021.107CrossRef

Rump K, Adamzik M (2022) Epigenetic mechanisms of postoperative cognitive impairment induced by anesthesia and neuroinflammation. Cells. https://doi.org/10.3390/cells11192954CrossRefPubMedPubMedCentral

Skvarc DR, Berk M, Byrne LK, Dean OM, Dodd S, Lewis M, Gray L (2018) Post-operative cognitive dysfunction: an exploration of the inflammatory hypothesis and novel therapies. Neurosci Biobehav Rev 84:116–133. https://doi.org/10.1016/j.neubiorev.2017.11.011CrossRefPubMed

Tang XL, Wang X, Fang G, Zhao YL, Yan J, Zhou Z, Li SY (2021) Resveratrol ameliorates sevoflurane-induced cognitive impairment by activating the SIRT1/NF-κB pathway in neonatal mice. J Nutr Biochem 90:108579. https://doi.org/10.1016/j.jnutbio.2020.108579CrossRefPubMed

Tang Y, Zhou X, Cao T, Chen E, Li Y, Lei W, Liu S (2022) Endoplasmic reticulum stress and oxidative stress in inflammatory diseases. DNA Cell Biol 41:924–934. https://doi.org/10.1089/dna.2022.0353CrossRefPubMed

Teleanu DM, Niculescu AG, Lungu II, Radu CI, Vladâcenco O, Roza E, Teleanu RI (2022) An overview of oxidative stress, neuroinflammation, and neurodegenerative diseases. Int J Mol Sci. https://doi.org/10.3390/ijms23115938CrossRefPubMedPubMedCentral

Tian Y, Chen KY, Liu LD, Dong YX, Zhao P, Guo SB (2018) Sevoflurane exacerbates cognitive impairment induced by Aβ (1–40) in rats through initiating neurotoxicity, neuroinflammation, and neuronal apoptosis in rat hippocampus. Mediators Inflamm 2018:3802324. https://doi.org/10.1155/2018/3802324CrossRefPubMedPubMedCentral

Wang CM, Chen WC, Zhang Y, Lin S, He HF (2021) Update on the mechanism and treatment of sevoflurane-induced postoperative cognitive dysfunction. Front Aging Neurosci 13:702231. https://doi.org/10.3389/fnagi.2021.702231CrossRefPubMedPubMedCentral

Wu D, Chen Y, Sun Y, Gao Q, Li H, Yang Z, Yu B (2020) Target of MCC950 in inhibition of NLRP3 inflammasome activation: a literature review. Inflammation 43:17–23. https://doi.org/10.1007/s10753-019-01098-8CrossRefPubMed

Xu L, Liu Z, Wang H, Lu J, Xu J, Meng Y, Liu B (2023) SESN2 could be a potential marker for diagnosis and prognosis in glioma. Genes (basel). https://doi.org/10.3390/genes14030701CrossRefPubMedPubMedCentral

Yi W, Zhang Y, Guo Y, Li D, Li X (2015) Elevation of Sestrin-2 expression attenuates Sevoflurane induced neurotoxicity. Metab Brain Dis 30:1161–1166. https://doi.org/10.1007/s11011-015-9673-1CrossRefPubMed

Yu XW, Curlik DM, Oh MM, Yin JC, Disterhoft JF (2017) CREB overexpression in dorsal CA1 ameliorates long-term memory deficits in aged rats. Elife. https://doi.org/10.7554/eLife.19358CrossRefPubMedPubMedCentral

Zhang LL, Zhang ZJ (2018) Sestrin2 aggravates oxidative stress of neurons by decreasing the expression of Nrf2. Eur Rev Med Pharmacol Sci 22:3493–3501. https://doi.org/10.26355/eurrev_201806_15176CrossRefPubMed

Zhang Y, Gao Y, Yang F, Wu X, Tang Z, Liu H (2022) Neuroglobin alleviates the neurotoxicity of sevoflurane to fetal rats by inhibiting neuroinflammation and affecting microglial polarization. Brain Res Bull 183:142–152. https://doi.org/10.1016/j.brainresbull.2022.03.006CrossRefPubMed

Zhao L, Gong H, Huang H, Tuerhong G, Xia H (2021) Participation of mind bomb-2 in Sevoflurane anesthesia induces cognitive impairment in aged mice via modulating ferroptosis. ACS Chem Neurosci 12:2399–2408. https://doi.org/10.1021/acschemneuro.1c00131CrossRefPubMed

Title: SESN2 attenuates sevoflurane-induced cognitive impairment and neuroinflammation in rats
Authors: Li Sun
Yangyang Li
Daliang Wang
Xiaoya Hong
Publication date: 21-12-2023
Publisher: Springer Berlin Heidelberg
Keyword: Sevoflurane
Published in: Experimental Brain Research / Issue 2/2024
Print ISSN: 0014-4819
Electronic ISSN: 1432-1106
DOI: https://doi.org/10.1007/s00221-023-06757-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

SESN2 attenuates sevoflurane-induced cognitive impairment and neuroinflammation in rats

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2024

Vestibular contributions to linear motion perception

Investigation of non-invasive focused ultrasound efficacy on depressive-like behavior in hemiparkinsonian rats

Anesthesia/surgery-induced learning and memory dysfunction by inhibiting mitophagy-mediated NLRP3 inflammasome inactivation in aged mice

LncRNA-mir3471-limd1 regulatory network plays critical roles in HIBD

The ultrastructure of macaque mesencephalic trigeminal nucleus neurons

Modulation of motor surround inhibition during motor tasks