{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T03:46:08Z","timestamp":1788925568748,"version":"build-2803163510"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T00:00:00Z","timestamp":1638230400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81371195"],"award-info":[{"award-number":["81371195"]}],"id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81870851"],"award-info":[{"award-number":["81870851"]}],"id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012659","name":"Foundation for Innovative Research Groups of the National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071208"],"award-info":[{"award-number":["82071208"]}],"id":[{"id":"10.13039\/501100012659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Neurosci."],"abstract":"<jats:p>Postoperative cognitive dysfunction (POCD) is a common postoperative neurocognitive complication in elderly patients. However, the specific pathogenesis is unknown, and it has been demonstrated that neuroinflammation plays a key role in POCD. Recently, increasing evidence has proven that the locus coeruleus noradrenergic (LCNE) system participates in regulating neuroinflammation in some neurodegenerative disorders. We hypothesize that LCNE plays an important role in the neuroinflammation of POCD. In this study, 400 \u03bcg of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was injected intracerebroventricularly into each rat 7 days before anesthesia\/surgery to deplete the locus coeruleus (LC) noradrenaline (NE). We applied a simple laparotomy and brief upper mesenteric artery clamping surgery as the rat POCD model. The open field test, novel objection and novel location (NL) recognition, and Morris water maze (MWM) were performed to assess postoperative cognition. High-performance liquid chromatography (HPLC) was used to measure the level of NE in plasma and brain tissues, and immunofluorescence staining was applied to evaluate the activation of microglia and astrocytes. We also used enzyme-linked immune-sorbent assay (ELISA) to assess the levels of inflammatory cytokines and brain-derived neurotrophic factor (BDNF). Pretreatment with DSP-4 decreased the levels of systemic and central NE, increased the level of interleukin-6 (IL-6) in the plasma at 6 h after the surgery, decreased the concentration of IL-6 in the prefrontal cortex and hippocampus, and decreased the level of interleukin-1\u03b2 (IL-1\u03b2) in the plasma, prefrontal cortex, and hippocampus at 1 week postoperatively. In addition, DSP-4 treatment attenuated hippocampal-dependent learning and memory impairment in rats with POCD, with a downregulation of the activation of microglia and astrocytes in the prefrontal cortex and hippocampus. In conclusion, these findings provide evidence of the effects of LCNE in modulating neuroinflammation in rats with POCD and provide a new perspective in the prevention and treatment of POCD.<\/jats:p>","DOI":"10.3389\/fnmol.2021.752838","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T19:25:51Z","timestamp":1638386751000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["A Noradrenergic Lesion Attenuates Surgery-Induced Cognitive Impairment in Rats by Suppressing Neuroinflammation"],"prefix":"10.3389","volume":"14","author":[{"given":"Jiayu","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meimei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mian","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.bbi.2018.09.004","article-title":"The \u03b22-adrenergic receptor controls inflammation by driving rapid il-10 secretion.","volume":"74","author":"A\u011fa\u00e7","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"B2","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1016\/j.ebiom.2018.10.021","article-title":"Surgery, neuroinflammation and cognitive impairment.","volume":"37","author":"Alam","year":"2018","journal-title":"EBioMedicine"},{"key":"B3","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1476-5381.1984.tb16465.x","article-title":"Aparametric study of the effects of the noradrenaline neurotoxin dsp4 on avoidance acquisition and noradrenaline neurones in the cns of the rat.","volume":"82","author":"Archer","year":"1984","journal-title":"Br. J. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1146\/annurev.neuro.28.061604.135709","article-title":"An integrative theory of locus coeruleus-norepinephrine function: adaptive gain and optimal performance.","volume":"28","author":"Aston-Jones","year":"2005","journal-title":"Annu. Rev. Neurosci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/j.psyneuen.2019.01.026","article-title":"Sex differences in the regulation of brain il-1\u03b2 in response to chronic stress.","volume":"103","author":"Barnard","year":"2019","journal-title":"Psychoneuroendocrino"},{"key":"B6","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s00441-017-2649-1","article-title":"Locus coeruleus.","volume":"373","author":"Benarroch","year":"2018","journal-title":"Cell Tissue Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"2558","DOI":"10.1093\/brain\/awz193","article-title":"Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases.","volume":"142","author":"Betts","year":"2019","journal-title":"Brain"},{"key":"B8","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/j.yebeh.2015.04.046","article-title":"Aberrant hippocampal neurogenesis after limbic kindling: relationship to bdnf and hippocampal-dependent memory.","volume":"47","author":"Botterill","year":"2015","journal-title":"Epilepsy Behav."},{"key":"B9","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1126\/science.aan8868","article-title":"What constitutes the prefrontal cortex?","volume":"358","author":"Carlen","year":"2017","journal-title":"Science"},{"key":"B10","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.expneurol.2012.06.033","article-title":"Age-dependent decline of motor neocortex but not hippocampal performance in heterozygous bdnf mice correlates with a decrease of cortical psd-95 but an increase of hippocampal trkb levels.","volume":"237","author":"Carret\u00f3n","year":"2012","journal-title":"Exp. Neurol."},{"key":"B11","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1523\/JNEUROSCI.1483-17.2017","article-title":"Locus coeruleus ablation exacerbates cognitive deficits, neuropathology, and lethality in p301s tau transgenic mice.","volume":"38","author":"Chalermpalanupap","year":"2018","journal-title":"J. Neurosci."},{"key":"B12","article-title":"Participation of noradrenergic neurotransmission in angiotensin iii-induced dipsogenic behavior in the rat.","volume":"48","author":"Chan","year":"1991","journal-title":"Life Sci."},{"key":"B13","doi-asserted-by":"publisher","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":"B14","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-1-9","article-title":"Inhibition of microglial inflammatory responses by norepinephrine: effects on nitric oxide and interleukin-1\u03b2 production.","volume":"1","author":"Dello Russo","year":"2004","journal-title":"J. Neuroinflamm."},{"key":"B15","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1007\/s00281-019-00764-1","article-title":"Resolution of neuroinflammation: mechanisms and potential therapeutic option.","volume":"41","author":"Dokalis","year":"2019","journal-title":"Semin. Immunopathol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1016\/j.neuropharm.2013.05.043","article-title":"Pre- and postsynaptic twists in bdnf secretion and action in synaptic plasticity.","volume":"76","author":"Edelmann","year":"2014","journal-title":"Neuropharmacology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2369","DOI":"10.1523\/JNEUROSCI.1661-18.2019","article-title":"Lactate mediates the effects of exercise on learning and memory through sirt1-dependent activation of hippocampal brain-derived neurotrophic factor (bdnf).","volume":"39","author":"El Hayek","year":"2019","journal-title":"J. Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.bbi.2019.01.021","article-title":"The contribution of the locus coeruleus-norepinephrine system in the emergence of defeat-induced inflammatory priming.","volume":"79","author":"Finnell","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"B19","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/s0079-6123(08)63815-7","article-title":"Selective effects of dsp-4 on locus coeruleus axons: are there pharmacologically different types of noradrenergic axons in the central nervous system?","volume":"88","author":"Fritschy","year":"1991","journal-title":"Prog. Brain Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1016\/j.neuroscience.2010.07.052","article-title":"Noradrenaline release in the locus coeruleus modulates memory formation and consolidation; Roles for \u03b1- and \u03b2-adrenergic receptors.","volume":"170","author":"Gibbs","year":"2010","journal-title":"Neuroscience"},{"key":"B21","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/S0301-0082(02)00023-0","article-title":"Role of adrenoceptor subtypes in memory consolidation.","volume":"67","author":"Gibbs","year":"2002","journal-title":"Prog. Neurobiol."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228630","article-title":"Locus coeruleus modulates neuroinflammation in parkinsonism and dementia.","volume":"21","author":"Giorgi","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1016\/j.drudis.2021.01.019","article-title":"Postoperative cognitive dysfunction: an acute approach for the development of novel treatments for neuroinflammation.","volume":"26","author":"Granger","year":"2021","journal-title":"Drug Discov. Today"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2727602","article-title":"The longevity of hippocampus-dependent memory is orchestrated by the locus coeruleus-noradrenergic system.","volume":"2017","author":"Hansen","year":"2017","journal-title":"Neural Plast."},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0681-9","article-title":"Perioperative cerebrospinal fluid and plasma inflammatory markers after orthopedic surgery.","volume":"13","author":"Hirsch","year":"2016","journal-title":"J. Neuroinflamm."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0332-6","article-title":"Systemic inflammation and microglial activation: systematic review of animal experiments.","volume":"12","author":"Hoogland","year":"2015","journal-title":"J. Neuroinflamm."},{"key":"B27","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.bbi.2014.02.002","article-title":"Postoperative cognitive dysfunction: involvement of neuroinflammation and neuronal functioning.","volume":"38","author":"Hovens","year":"2014","journal-title":"Brain Behav. Immun."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/j.exger.2013.07.011","article-title":"Surgery-induced behavioral changes in aged rats.","volume":"48","author":"Hovens","year":"2013","journal-title":"Exp. Gerontol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.bja.2017.11.096","article-title":"Interleukin-6 is both necessary and sufficient to produce perioperative neurocognitive disorder in mice.","volume":"120","author":"Hu","year":"2018","journal-title":"Br. J. Anaesth."},{"key":"B30","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/s41590-018-0064-8","article-title":"Innate immune responses to trauma.","volume":"19","author":"Huber-Lang","year":"2018","journal-title":"Nat. Immunol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/j.neuroscience.2005.06.090","article-title":"Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines.","volume":"135","author":"Johnson","year":"2005","journal-title":"Neuroscience"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1016\/j.bbi.2008.03.007","article-title":"Role of central \u03b2-adrenergic receptors in regulating proinflammatory cytokine responses to a peripheral bacterial challenge.","volume":"22","author":"Johnson","year":"2008","journal-title":"Brain Behav. Immun."},{"key":"B33","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/0014-2999(81)90272-7","article-title":"Dsp4 (n-(2-chloroethyl)-n-ethyl-2-bromobenzylamine)\u2013a useful denervation tool for central and peripheral noradrenaline neurons.","volume":"72","author":"Jonsson","year":"1981","journal-title":"Eur. J. Pharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1007\/s10787-019-00580-x","article-title":"Activation of microglia and astrocytes: a roadway to neuroinflammation and Alzheimer\u2019s disease.","volume":"27","author":"Kaur","year":"2019","journal-title":"Inflammopharmacology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.neulet.2011.07.056","article-title":"Antinociceptive effects of neurotropin in a rat model of central neuropathic pain: dsp-4 induced noradrenergic lesion.","volume":"503","author":"Kudo","year":"2011","journal-title":"Neurosci. Lett."},{"key":"B36","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1097\/ALN.0000000000003390","article-title":"Dexmedetomidine exerts an anti-inflammatory effect via \u03b12 adrenoceptors to prevent lipopolysaccharide-induced cognitive decline in mice.","volume":"133","author":"Li","year":"2020","journal-title":"Anesthesiology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"3295","DOI":"10.1007\/s12035-018-1283-6","article-title":"Brain-derived neurotrophic factor in brain disorders: focus on neuroinflammation.","volume":"56","author":"Lima Giacobbo","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01761-0","article-title":"Astrocyte-derived exosomes enriched with mir-873a-5p inhibit neuroinflammation via microglia phenotype modulation after traumatic brain injury.","volume":"17","author":"Long","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1111\/j.1478-3231.2010.02211.x","article-title":"Tumour necrosis factor-alpha affects blood-brain barrier permeability and tight junction-associated occludin in acute liver failure.","volume":"30","author":"Lv","year":"2010","journal-title":"Liver Int."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1017\/S0140525X15000667","article-title":"Norepinephrine ignites local hotspots of neuronal excitation: how arousal amplifies selectivity in perception and memory.","volume":"39","author":"Mather","year":"2016","journal-title":"Behav. Brain Sci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1007\/s00109-011-0784-9","article-title":"Cellular and molecular choreography of neutrophil recruitment to sites of sterile inflammation.","volume":"89","author":"McDonald","year":"2011","journal-title":"J. Mol. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/nature07201","article-title":"Origin and physiological roles of inflammation.","volume":"454","author":"Medzhitov","year":"2008","journal-title":"Nature"},{"key":"B43","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1002\/glia.22930","article-title":"Sequential activation of microglia and astrocyte cytokine expression precedes increased iba-1 or gfap immunoreactivity following systemic immune challenge.","volume":"64","author":"Norden","year":"2016","journal-title":"Glia"},{"key":"B44","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.bbi.2020.12.002","article-title":"Acute neuroinflammation, sickness behavior and working memory in response to acute systemic challenge with lps following noradrenergic lesion in mice.","volume":"94","author":"O\u2019Neill","year":"2020","journal-title":"Brain Behav. Immun."},{"key":"B45","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1016\/j.neuropharm.2013.06.024","article-title":"Bdnf mechanisms in late ltp formation: a synthesis and breakdown.","volume":"76","author":"Panja","year":"2014","journal-title":"Neuropharmacology"},{"key":"B46","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.neuropharm.2014.12.020","article-title":"Immune dysregulation and cognitive vulnerability in the aging brain: interactions of microglia, il-1\u03b2, bdnf and synaptic plasticity.","volume":"96","author":"Patterson","year":"2015","journal-title":"Neuropharmacology"},{"key":"B47","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1093\/brain\/awq362","article-title":"Locus coeruleus damage and noradrenaline reductions in multiple sclerosis and experimental autoimmune encephalomyelitis.","volume":"134","author":"Polak","year":"2011","journal-title":"Brain"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.667705","article-title":"The role of distinct subsets of macrophages in the pathogenesis of ms and the impact of different therapeutic agents on these populations.","volume":"12","author":"Radandish","year":"2021","journal-title":"Front Immunol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neubiorev.2021.09.023","article-title":"The emerging tale of microglia in psychiatric disorders.","volume":"131","author":"Rahimian","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B50","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1017\/S0033291700003032","article-title":"Cortical noradrenaline, attention and arousal1.","volume":"14","author":"Robbins","year":"1984","journal-title":"Psychol. Med."},{"key":"B51","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/nrn2573","article-title":"The locus coeruleus and noradrenergic modulation of cognition.","volume":"10","author":"Sara","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"R1051","DOI":"10.1016\/j.cub.2015.09.039","article-title":"Organization of the locus coeruleus-norepinephrine system.","volume":"25","author":"Schwarz","year":"2015","journal-title":"Curr. Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.neuroscience.2009.08.046","article-title":"Central noradrenergic depletion by dsp-4 prevents stress-induced memory impairments in the object recognition task.","volume":"164","author":"Scullion","year":"2009","journal-title":"Neuroscience"},{"key":"B54","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1093\/bja\/aex238","article-title":"Thinking, fast and slow: highlights from the 2016 bja seminar on anaesthetic neurotoxicity and neuroplasticity.","volume":"119","author":"Soriano","year":"2017","journal-title":"Br. J. Anaesth."},{"key":"B55","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1097\/ALN.0b013e318195b569","article-title":"Long-term consequences of postoperative cognitive dysfunction.","volume":"110","author":"Steinmetz","year":"2009","journal-title":"Anesthesiology"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1782","DOI":"10.1038\/s41593-019-0514-0","article-title":"Noradrenergic signaling in the wakeful state inhibits microglial surveillance and synaptic plasticity in the mouse visual cortex.","volume":"22","author":"Stowell","year":"2019","journal-title":"Nat. Neurosci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1213\/ANE.0000000000004053","article-title":"Neuroinflammation and perioperative neurocognitive disorders.","volume":"128","author":"Subramaniyan","year":"2019","journal-title":"Anesthesia Analgesia"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1632-z","article-title":"Stress-induced microglial activation occurs through \u03b2-adrenergic receptor: noradrenaline as a key neurotransmitter in microglial activation.","volume":"16","author":"Sugama","year":"2019","journal-title":"J. Neuroinflamm."},{"key":"B59","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.cellsig.2006.06.007","article-title":"B 2 adrenergic receptor activation stimulates pro-inflammatory cytokine production in macrophages via pka- and nf-\u03bab-independent mechanisms.","volume":"19","author":"Tan","year":"2007","journal-title":"Cell. Signal."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1007\/s12035-014-9070-5","article-title":"Differential roles of m1 and m2 microglia in neurodegenerative diseases.","volume":"53","author":"Tang","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"B61","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/BF00687399","article-title":"Effects of the noradrenaline neurotoxin n-2-chloroethyl-n-ethyl-2-bromo-benzylamine hydrochloride (dsp 4) on the blood-brain barrier.","volume":"78","author":"Tengvar","year":"1989","journal-title":"Acta Neuropathol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1002\/ana.22664","article-title":"Resolving postoperative neuroinflammation and cognitive decline.","volume":"70","author":"Terrando","year":"2011","journal-title":"Ann. Neurol."},{"key":"B63","article-title":"Spatial navigation (water maze) tasks","author":"Terry","year":"2009","journal-title":"Methods of Behavior Analysis in Neuroscience"},{"key":"B64","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.expneurol.2015.11.014","article-title":"Low-frequency stimulation in anterior nucleus of thalamus alleviates kainate-induced chronic epilepsy and modulates the hippocampal eeg rhythm.","volume":"276","author":"Wang","year":"2016","journal-title":"Exp. Neurol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.bbr.2017.05.066","article-title":"Astrocyte-derived ccl2 participates in surgery-induced cognitive dysfunction and neuroinflammation via evoking microglia activation.","volume":"332","author":"Xu","year":"2017","journal-title":"Behav. Brain Res."},{"key":"B66","doi-asserted-by":"publisher","first-page":"1","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":"B67","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1016\/j.bja.2018.10.062","article-title":"Maresin 1 attenuates neuroinflammation in a mouse model of perioperative neurocognitive disorders.","volume":"122","author":"Yang","year":"2019","journal-title":"Brit. J. Anaesth."},{"key":"B68","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1016\/j.brainres.2015.08.032","article-title":"Lesion of the locus coeruleus aggravates dopaminergic neuron degeneration by modulating microglial function in mouse models of Parkinson\u2019s disease.","volume":"1625","author":"Yao","year":"2015","journal-title":"Brain Res."},{"key":"B69","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.bbi.2010.10.015","article-title":"Immune modulation of learning, memory, neural plasticity and neurogenesis.","volume":"25","author":"Yirmiya","year":"2011","journal-title":"Brain Behav. Immun."},{"key":"B70","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.bbi.2018.06.017","article-title":"Sustained stimulation of \u03b22- and \u03b23-adrenergic receptors leads to persistent functional pain and neuroinflammation.","volume":"73","author":"Zhang","year":"2018","journal-title":"Brain Behav. Immun."},{"key":"B71","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1146\/annurev-pathmechdis-012419-032847","article-title":"Damps, pamps, and lamps in immunity and sterile inflammation.","volume":"15","author":"Zindel","year":"2020","journal-title":"Annu. Rev. Pathol."}],"container-title":["Frontiers in Molecular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2021.752838\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T19:25:57Z","timestamp":1638386757000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnmol.2021.752838\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,30]]},"references-count":71,"alternative-id":["10.3389\/fnmol.2021.752838"],"URL":"https:\/\/doi.org\/10.3389\/fnmol.2021.752838","relation":{},"ISSN":["1662-5099"],"issn-type":[{"value":"1662-5099","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,30]]},"article-number":"752838"}}