{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:38:26Z","timestamp":1791409106571,"version":"4.3.3"},"reference-count":80,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T00:00:00Z","timestamp":1678665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771159"],"award-info":[{"award-number":["81771159"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81974160"],"award-info":[{"award-number":["81974160"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2020YFC2009002"],"award-info":[{"award-number":["2020YFC2009002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R &amp; D Program of China","doi-asserted-by":"publisher","award":["81771159"],"award-info":[{"award-number":["81771159"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R &amp; D Program of China","doi-asserted-by":"publisher","award":["81974160"],"award-info":[{"award-number":["81974160"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key R &amp; D Program of China","doi-asserted-by":"publisher","award":["2020YFC2009002"],"award-info":[{"award-number":["2020YFC2009002"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Postoperative cognitive dysfunction (POCD) is a severe neurological complication after anesthesia and surgery. However, there is still a lack of effective clinical pharmacotherapy due to its unclear pathogenesis. Caffeic acid phenethyl ester (CAPE), which is obtained from honeybee propolis and medicinal plants, shows powerful antioxidant, anti-inflammatory, and immunomodulating properties. In this study, we aimed to evaluate whether CAPE mitigated cognitive impairment following anesthesia and surgery and its potential underlying mechanisms in aged mice. Here, isoflurane anesthesia and tibial fracture surgery were used as the POCD model, and H2O2-induced BV2 cells were established as the microglial oxidative stress model. We revealed that CAPE pretreatment suppressed oxidative stress and promoted the switch of microglia from the M1 to the M2 type in the hippocampus, thereby ameliorating cognitive impairment caused by anesthesia and surgery. Further investigation indicated that CAPE pretreatment upregulated hippocampal Sirt6\/Nrf2 expression after anesthesia and surgery. Moreover, mechanistic studies in BV2 cells demonstrated that the potent effects of CAPE pretreatment on reducing ROS generation and promoting protective polarization were attenuated by a specific Sirt6 inhibitor, OSS_128167. In summary, our findings opened a promising avenue for POCD prevention through CAPE pretreatment that enhanced the Sirt6\/Nrf2 pathway to suppress oxidative stress as well as favor microglia protective polarization.<\/jats:p>","DOI":"10.3390\/antiox12030714","type":"journal-article","created":{"date-parts":[[2023,3,14]],"date-time":"2023-03-14T03:29:16Z","timestamp":1678764556000},"page":"714","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Caffeic Acid Phenethyl Ester Suppresses Oxidative Stress and Regulates M1\/M2 Microglia Polarization via Sirt6\/Nrf2 Pathway to Mitigate Cognitive Impairment in Aged Mice following Anesthesia and Surgery"],"prefix":"10.3390","volume":"12","author":[{"given":"Yue","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziwen","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaofeng","family":"Zhan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-7541","authenticated-orcid":false,"given":"Xing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7442-1826","authenticated-orcid":false,"given":"Shiyong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ailin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Hubei Key Laboratory of Geriatric Anesthesia and Perioperative Brain Health, Wuhan Clinical Research Center for Geriatric Anesthesia, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e171505","DOI":"10.1001\/jamasurg.2017.1505","article-title":"Intraoperative Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery: A Randomized Clinical Trial","volume":"152","author":"Deiner","year":"2017","journal-title":"JAMA Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1097\/ALN.0000000000004439","article-title":"Prevention of Postoperative Cognitive Dysfunction by Minocycline in Elderly Patients after Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial","volume":"138","author":"Takazawa","year":"2023","journal-title":"Anesthesiology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0140-6736(97)07382-0","article-title":"Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction","volume":"351","author":"Moller","year":"1998","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2874","DOI":"10.1161\/hs1201.099803","article-title":"Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery","volume":"32","author":"Newman","year":"2001","journal-title":"Stroke"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1056\/NEJM200102083440601","article-title":"Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery","volume":"344","author":"Newman","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1038\/cr.2012.10","article-title":"Microglial migration mediated by ATP-induced ATP release from lysosomes","volume":"22","author":"Dou","year":"2012","journal-title":"Cell Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5521503","DOI":"10.1155\/2021\/5521503","article-title":"Bu Shen Yi Sui Capsule Alleviates Neuroinflammation and Demyelination by Promoting Microglia toward M2 Polarization, Which Correlates with Changes in miR-124 and miR-155 in Experimental Autoimmune Encephalomyelitis","volume":"2021","author":"Zha","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4751349","DOI":"10.1155\/2020\/4751349","article-title":"Baicalin Ameliorates Cognitive Impairment and Protects Microglia from LPS-Induced Neuroinflammation via the SIRT1\/HMGB1 Pathway","volume":"2020","author":"Li","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/nrneurol.2017.69","article-title":"Modulators of microglial activation and polarization after intracerebral haemorrhage","volume":"13","author":"Lan","year":"2017","journal-title":"Nat. Rev. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"104253","DOI":"10.1016\/j.phrs.2019.104253","article-title":"Natural products as a potential modulator of microglial polarization in neurodegenerative diseases","volume":"145","author":"Jin","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13195-015-0139-9","article-title":"Immune phenotypes of microglia in human neurodegenerative disease: Challenges to detecting microglial polarization in human brains","volume":"7","author":"Walker","year":"2015","journal-title":"Alzheimers Res. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.bbi.2017.03.003","article-title":"Resveratrol regulates microglia M1\/M2 polarization via PGC-1alpha in conditions of neuroinflammatory injury","volume":"64","author":"Yang","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e12774","DOI":"10.1111\/acel.12774","article-title":"Antagonizing peroxisome proliferator-activated receptor gamma facilitates M1-to-M2 shift of microglia by enhancing autophagy via the LKB1-AMPK signaling pathway","volume":"17","author":"Ji","year":"2018","journal-title":"Aging Cell"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"102297","DOI":"10.1016\/j.redox.2022.102297","article-title":"Icariin alleviates uveitis by targeting peroxiredoxin 3 to modulate retinal microglia M1\/M2 phenotypic polarization","volume":"52","author":"Wang","year":"2022","journal-title":"Redox. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3208","DOI":"10.1038\/s41467-021-23545-7","article-title":"Restoration of energy homeostasis by SIRT6 extends healthy lifespan","volume":"12","author":"Roichman","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5244","DOI":"10.1038\/s41467-020-19018-y","article-title":"Multivalent interactions drive nucleosome binding and efficient chromatin deacetylation by SIRT6","volume":"11","author":"Liu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7914","DOI":"10.1093\/nar\/gkz528","article-title":"SIRT6 promotes transcription of a subset of NRF2 targets by mono-ADP-ribosylating BAF170","volume":"47","author":"Rezazadeh","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"109035","DOI":"10.1016\/j.celrep.2021.109035","article-title":"SIRT6-CBP-dependent nuclear Tau accumulation and its role in protein synthesis","volume":"35","author":"Portillo","year":"2021","journal-title":"Cell Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1007\/s12035-021-02671-9","article-title":"Blood Circulatory Level of Seven Sirtuins in Alzheimer\u2019s Disease: Potent Biomarker Based on Translational Research","volume":"59","author":"Pradhan","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Okun, E., Marton, D., Cohen, D., Griffioen, K., Kanfi, Y., Illouz, T., Madar, R., and Cohen, H.Y. (2017). Sirt6 alters adult hippocampal neurogenesis. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0179681"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/s41419-022-04866-x","article-title":"Energy restriction induced SIRT6 inhibits microglia activation and promotes angiogenesis in cerebral ischemia via transcriptional inhibition of TXNIP","volume":"13","author":"Song","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.apsb.2020.11.002","article-title":"A novel SIRT6 activator ameliorates neuroinflammation and ischemic brain injury via EZH2\/FOXC1 axis","volume":"11","author":"He","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"128010","DOI":"10.1016\/j.jhazmat.2021.128010","article-title":"The genotoxic potential of mixed nitrosamines in drinking water involves oxidative stress and Nrf2 activation","volume":"426","author":"Dong","year":"2022","journal-title":"J. Hazard. Mater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3050971","DOI":"10.1155\/2020\/3050971","article-title":"Nrf2 Ablation Promotes Alzheimer\u2019s Disease-Like Pathology in APP\/PS1 Transgenic Mice: The Role of Neuroinflammation and Oxidative Stress","volume":"2020","author":"Ren","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7274342","DOI":"10.1155\/2020\/7274342","article-title":"Caffeic Acid Phenethyl Ester Protects against Experimental Autoimmune Encephalomyelitis by Regulating T Cell Activities","volume":"2020","author":"Zhou","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8239642","DOI":"10.1155\/2019\/8239642","article-title":"FA-97, a New Synthetic Caffeic Acid Phenethyl Ester Derivative, Protects against Oxidative Stress-Mediated Neuronal Cell Apoptosis and Scopolamine-Induced Cognitive Impairment by Activating Nrf2\/HO-1 Signaling","volume":"2019","author":"Wan","year":"2019","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5572","DOI":"10.3390\/ijms16035572","article-title":"Regulatory effects of caffeic acid phenethyl ester on neuroinflammation in microglial cells","volume":"16","author":"Tsai","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.2174\/1570159X19666210608165509","article-title":"Neuroprotective Potential of Caffeic Acid Phenethyl Ester (CAPE) in CNS Disorders: Mechanistic and Therapeutic Insights","volume":"19","author":"Kulkarni","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"605","DOI":"10.14336\/AD.2017.0903","article-title":"Neuroprotective Effect of Caffeic Acid Phenethyl Ester in A Mouse Model of Alzheimer\u2019s Disease Involves Nrf2\/HO-1 Pathway","volume":"9","author":"Morroni","year":"2018","journal-title":"Aging Dis."},{"key":"ref_30","first-page":"1555","article-title":"The role of SIRT1 in neuroinflammation and cognitive dysfunction in aged rats after anesthesia and surgery","volume":"11","author":"Yan","year":"2019","journal-title":"Am. J. Transl. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4635163","DOI":"10.1155\/2020\/4635163","article-title":"Resveratrol Mitigates Hippocampal Tau Acetylation and Cognitive Deficit by Activation SIRT1 in Aged Rats following Anesthesia and Surgery","volume":"2020","author":"Yan","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1097\/ALN.0000000000000697","article-title":"Impact of Preoperative Environmental Enrichment on Prevention of Development of Cognitive Impairment following Abdominal Surgery in a Rat Model","volume":"123","author":"Kawano","year":"2015","journal-title":"Anesthesiology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1213\/ANE.0000000000001675","article-title":"Fragmented Sleep Enhances Postoperative Neuroinflammation but Not Cognitive Dysfunction","volume":"124","author":"Vacas","year":"2017","journal-title":"Anesth. Analg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1097\/ALN.0b013e318286d0c9","article-title":"Surgery results in exaggerated and persistent cognitive decline in a rat model of the Metabolic Syndrome","volume":"118","author":"Feng","year":"2013","journal-title":"Anesthesiology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102280","DOI":"10.1016\/j.pneurobio.2022.102280","article-title":"MST1 mediates neuronal loss and cognitive deficits: A novel therapeutic target for Alzheimer\u2019s disease","volume":"214","author":"Wang","year":"2022","journal-title":"Prog. Neurobiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8797","DOI":"10.7150\/thno.61601","article-title":"Activating AhR alleviates cognitive deficits of Alzheimer\u2019s disease model mice by upregulating endogenous Abeta catabolic enzyme Neprilysin","volume":"11","author":"Qian","year":"2021","journal-title":"Theranostics"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e13037","DOI":"10.1111\/acel.13037","article-title":"Lifelong choline supplementation ameliorates Alzheimer\u2019s disease pathology and associated cognitive deficits by attenuating microglia activation","volume":"18","author":"Velazquez","year":"2019","journal-title":"Aging Cell"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"748637","DOI":"10.3389\/fnagi.2021.748637","article-title":"Cefazolin Improves Anesthesia and Surgery-Induced Cognitive Impairments by Modulating Blood-Brain Barrier Function, Gut Bacteria and Short Chain Fatty Acids","volume":"13","author":"Luo","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s12974-021-02089-z","article-title":"Sirtuin 3 protects against anesthesia\/surgery-induced cognitive decline in aged mice by suppressing hippocampal neuroinflammation","volume":"18","author":"Liu","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6158","DOI":"10.1007\/s12035-022-02959-4","article-title":"HDAC6 Inhibition Alleviates Anesthesia and Surgery-Induced Less Medial Prefrontal-Dorsal Hippocampus Connectivity and Cognitive Impairment in Aged Rats","volume":"59","author":"Chen","year":"2022","journal-title":"Mol. Neurobiol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7167","DOI":"10.1038\/s41380-021-01291-y","article-title":"Appropriate exercise level attenuates gut dysbiosis and valeric acid increase to improve neuroplasticity and cognitive function after surgery in mice","volume":"26","author":"Lai","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.bbi.2017.01.005","article-title":"Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery","volume":"61","author":"Zheng","year":"2017","journal-title":"Brain Behav. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"14641","DOI":"10.1523\/JNEUROSCI.2173-12.2012","article-title":"Intracisternal interleukin-1 receptor antagonist prevents postoperative cognitive decline and neuroinflammatory response in aged rats","volume":"32","author":"Barrientos","year":"2012","journal-title":"J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1097\/00000542-200703000-00007","article-title":"Postoperative impairment of cognitive function in rats: A possible role for cytokine-mediated inflammation in the hippocampus","volume":"106","author":"Wan","year":"2007","journal-title":"Anesthesiology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.bbi.2018.07.016","article-title":"Oxidative stress and mitochondrial dysfunction contributes to postoperative cognitive dysfunction in elderly rats","volume":"73","author":"Netto","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.18632\/aging.101871","article-title":"Anesthesia and surgery induce cognitive dysfunction in elderly male mice: The role of gut microbiota","volume":"11","author":"Zhan","year":"2019","journal-title":"Aging"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.bbi.2014.10.011","article-title":"S100A8 contributes to postoperative cognitive dysfunction in mice undergoing tibial fracture surgery by activating the TLR4\/MyD88 pathway","volume":"44","author":"Lu","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1186\/s12974-019-1661-7","article-title":"BAP31 regulates IRAK1-dependent neuroinflammation in microglia","volume":"16","author":"Liu","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1567179","DOI":"10.1155\/2019\/1567179","article-title":"Irisin Attenuates Neuroinflammation and Prevents the Memory and Cognitive Deterioration in Streptozotocin-Induced Diabetic Mice","volume":"2019","author":"Wang","year":"2019","journal-title":"Mediat. Inflamm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1136\/svn-2021-001396","article-title":"Inhibition of the postsynaptic density protein 95 on the protective effect of Ang-(1-7)-Mas on cerebral ischaemia injury","volume":"7","author":"Zhao","year":"2022","journal-title":"Stroke Vasc. Neurol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3659","DOI":"10.7150\/ijbs.61399","article-title":"Downregulation of miR-23b by transcription factor c-Myc alleviates ischemic brain injury by upregulating Nrf2","volume":"17","author":"Xin","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.freeradbiomed.2018.06.029","article-title":"Trx-1 ameliorates learning and memory deficits in MPTP-induced Parkinson\u2019s disease model in mice","volume":"124","author":"Zhang","year":"2018","journal-title":"Free Radic. Biol. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s13024-021-00488-7","article-title":"Adult-onset CNS myelin sulfatide deficiency is sufficient to cause Alzheimer\u2019s disease-like neuroinflammation and cognitive impairment","volume":"16","author":"Qiu","year":"2021","journal-title":"Mol. Neurodegener."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.apsb.2019.03.003","article-title":"Matrine attenuates oxidative stress and cardiomyocyte apoptosis in doxorubicin-induced cardiotoxicity via maintaining AMPKalpha\/UCP2 pathway","volume":"9","author":"Hu","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1016\/j.ejim.2012.05.001","article-title":"Reduced heme oxygenase-1 expression in steatotic livers infected with hepatitis C virus","volume":"23","author":"Abdalla","year":"2012","journal-title":"Eur. J. Intern. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"367","DOI":"10.3892\/mmr.2021.12006","article-title":"SIRT6specific inhibitor OSS128167 exacerbates diabetic cardiomyopathy by aggravating inflammation and oxidative stress","volume":"23","author":"Huang","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1186\/s12974-022-02563-2","article-title":"Microglia-specific deletion of histone deacetylase 3 promotes inflammation resolution, white matter integrity, and functional recovery in a mouse model of traumatic brain injury","volume":"19","author":"Zhao","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/j.biopha.2018.02.089","article-title":"Caffeic acid phenethyl ester rescued streptozotocin-induced memory loss through PI3-kinase dependent pathway","volume":"101","author":"Kumar","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.biopha.2017.04.073","article-title":"Caffeic acid phenethyl ester protects the brain against hexavalent chromium toxicity by enhancing endogenous antioxidants and modulating the JAK\/STAT signaling pathway","volume":"91","author":"Mahmoud","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"671499","DOI":"10.3389\/fnagi.2021.671499","article-title":"The Role of Microglia in Perioperative Neuroinflammation and Neurocognitive Disorders","volume":"13","author":"Saxena","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.bbi.2019.01.020","article-title":"MicroRNA-146a protects against cognitive decline induced by surgical trauma by suppressing hippocampal neuroinflammation in mice","volume":"78","author":"Chen","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"114980","DOI":"10.1016\/j.bcp.2022.114980","article-title":"Melatonin improves cognitive function by suppressing endoplasmic reticulum stress and promoting synaptic plasticity during chronic cerebral hypoperfusion in rats","volume":"198","author":"Thangwong","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1007\/s12011-012-9564-9","article-title":"Surgical trauma induces iron accumulation and oxidative stress in a rodent model of postoperative cognitive dysfunction","volume":"151","author":"An","year":"2013","journal-title":"Biol. Trace Elem. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/s12974-016-0781-6","article-title":"Acetaminophen attenuates lipopolysaccharide-induced cognitive impairment through antioxidant activity","volume":"14","author":"Zhao","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"992869","DOI":"10.3389\/fncel.2022.992869","article-title":"Inhibition of the integrated stress response reverses oxidative stress damage-induced postoperative cognitive dysfunction","volume":"16","author":"Jiang","year":"2022","journal-title":"Front. Cell Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.freeradbiomed.2021.12.004","article-title":"Neuroinflammation-mediated mitochondrial dysregulation involved in postoperative cognitive dysfunction","volume":"178","author":"Yang","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"780880","DOI":"10.3389\/fncel.2022.780880","article-title":"Suppression of Neuroinflammation Attenuates Persistent Cognitive and Neurogenic Deficits in a Rat Model of Cardiopulmonary Bypass","volume":"16","author":"Wang","year":"2022","journal-title":"Front. Cell Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.bbi.2021.10.009","article-title":"Microglial glutaminase 1 deficiency mitigates neuroinflammation associated depression","volume":"99","author":"Ji","year":"2022","journal-title":"Brain Behav. Immun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.4103\/1673-5374.339489","article-title":"Exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation after traumatic brain injury","volume":"17","author":"Wen","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"114754","DOI":"10.1016\/j.bcp.2021.114754","article-title":"Roles of microglia in Alzheimer\u2019s disease and impact of new findings on microglial heterogeneity as a target for therapeutic intervention","volume":"192","author":"Takata","year":"2021","journal-title":"Biochem. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5434","DOI":"10.7150\/thno.27882","article-title":"Microglial TLR4-dependent autophagy induces ischemic white matter damage via STAT1\/6 pathway","volume":"8","author":"Qin","year":"2018","journal-title":"Theranostics"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e91229","DOI":"10.1172\/jci.insight.91229","article-title":"Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice","volume":"2","author":"Feng","year":"2017","journal-title":"JCI Insight"},{"key":"ref_73","first-page":"1","article-title":"Adipose sirtuin 6 drives macrophage polarization toward M2 through IL-4 production and maintains systemic insulin sensitivity in mice and humans","volume":"51","author":"Song","year":"2019","journal-title":"Exp. Mol. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.apsb.2020.06.016","article-title":"SIRT6 as a key event linking P53 and NRF2 counteracts APAP-induced hepatotoxicity through inhibiting oxidative stress and promoting hepatocyte proliferation","volume":"11","author":"Zhou","year":"2021","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.jhep.2019.06.019","article-title":"The epigenetic regulator SIRT6 protects the liver from alcohol-induced tissue injury by reducing oxidative stress in mice","volume":"71","author":"Kim","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Cheng, J., Fan, Y.Q., Zhang, W.F., Zhang, G., Zeng, K., Ye, Z., Zhao, D., Wu, L.Q., and Chen, Z.B. (2022). Overexpressing SIRT6 can Attenuate the Injury of Intracerebral Hemorrhage by Down-Regulating NF-kB. Neuromol. Med.","DOI":"10.1007\/s12017-022-08715-0"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1093\/eurheartj\/ehz712","article-title":"Endothelial SIRT6 blunts stroke size and neurological deficit by preserving blood-brain barrier integrity: A translational study","volume":"41","author":"Liberale","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1097\/ALN.0000000000001195","article-title":"Immune Modulation by Volatile Anesthetics","volume":"125","author":"Stollings","year":"2016","journal-title":"Anesthesiology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1038\/s41590-020-00812-1","article-title":"Neuroinflammation after surgery: From mechanisms to therapeutic targets","volume":"21","author":"Yang","year":"2020","journal-title":"Nat. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"111636","DOI":"10.1016\/j.fct.2020.111636","article-title":"Caffeic acid phenethyl ester reversed cadmium-induced cell death in hippocampus and cortex and subsequent cognitive disorders in mice: Involvements of AMPK\/SIRT1 pathway and amyloid-tau-neuroinflammation axis","volume":"144","author":"Hao","year":"2020","journal-title":"Food Chem. Toxicol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/3\/714\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:54:08Z","timestamp":1760122448000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/3\/714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,13]]},"references-count":80,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["antiox12030714"],"URL":"https:\/\/doi.org\/10.3390\/antiox12030714","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,13]]}}}