Abstract
The aging population is burgeoning globally and this trend presents great challenges to the current healthcare system as the growing number of aged individuals receives procedures of surgery and anesthesia. Postoperative cognitive dysfunction (POCD) is a severe postoperative neurological sequela. Advanced age is considered as an independent risk factor of POCD. Mounting evidence have shown that neuroinflammation plays an essential role in POCD. However, it remains debatable why this complication occurs highly in the aged individuals. As known, aging itself is the major common high-risk factor for age-associated disorders including diabetes, cardiovascular disease, cancer, and neurodegenerative diseases. Chronic low-grade neuroinflammation (dubbed neuroinflammaging in the present paper) is a hallmark alternation and contributes to age-related cognitive decline in the normal aging. Interestingly, several lines of findings show that the neuroinflammatory pathogenesis of POCD is age-dependent. It suggests that age-related changes, especially the neuroinflammaging, are possibly associated with the postoperative cognitive impairment. Understanding the role of neuroinflammaging in POCD is crucial to elucidate the mechanism of POCD and develop strategies to prevent or treat POCD. Here the focus of this review is on the potential role of neuroinflammaging in the mechanism of POCD. Lastly, we briefly review promising interventions for this neurological sequela.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ballabh P, Braun A, Nedergaard M (2004) The blood–brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis 16:1–13. https://doi.org/10.1016/j.nbd.2003.12.016
Barrientos RM, Hein AM, Frank MG, Watkins LR, Maier SF (2012) Intracisternal interleukin-1 receptor antagonist prevents postoperative cognitive decline and neuroinflammatory response in aged rats. J Neurosci 32:14641–14648. https://doi.org/10.1523/JNEUROSCI.2173-12.2012
Barrientos RM, Kitt MM, Watkins LR, Maier SF (2015) Neuroinflammation in the normal aging hippocampus. Neuroscience 309:84–99. https://doi.org/10.1016/j.neuroscience.2015.03.007
Barzilai N, Cuervo AM, Austad S (2018) Aging as a biological target for prevention and therapy. JAMA. https://doi.org/10.1001/jama.2018.9562
Ben Haim L, Rowitch DH (2017) Functional diversity of astrocytes in neural circuit regulation. Nat Rev Neurosci 18:31–41. https://doi.org/10.1038/nrn.2016.159
Bettio LEB, Rajendran L, Gil-Mohapel J (2017) The effects of aging in the hippocampus and cognitive decline. Neurosci Biobehav Rev 79:66–86. https://doi.org/10.1016/j.neubiorev.2017.04.030
Bi J, Shan W, Luo A, Zuo Z (2017) Critical role of matrix metallopeptidase 9 in postoperative cognitive dysfunction and age-dependent cognitive decline. Oncotarget 8:51817–51829. https://doi.org/10.18632/oncotarget.15545
Bisht K et al (2016) Dark microglia: a new phenotype predominantly associated with pathological states. Glia 64:826–839. https://doi.org/10.1002/glia.22966
Bussian TJ, Aziz A, Meyer CF, Swenson BL, van Deursen JM, Baker DJ (2018) Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline. Nature 562:578–582. https://doi.org/10.1038/s41586-018-0543-y
Cao XZ et al (2010) Postoperative cognitive deficits and neuroinflammation in the hippocampus triggered by surgical trauma are exacerbated in aged rats. Prog Neuropsychopharmacol Biol Psychiatry 34:1426–1432. https://doi.org/10.1016/j.pnpbp.2010.07.027
Cao Y et al (2018) Hypoxia-inducible factor-1α is involved in isoflurane-induced blood–brain barrier disruption in aged rats model of POCD. Behav Brain Res 339:39–46. https://doi.org/10.1016/j.bbr.2017.09.004
Castiglioni AJ, Legare ME, Busbee DL, Tiffany-Castiglioni E (1991) Morphological changes in astrocytes of aging mice fed normal or caloric restricted diets. Age 14:102–106. https://doi.org/10.1007/BF02435015
Cerbai F et al (2012) The neuron-astrocyte-microglia triad in normal brain ageing and in a model of neuroinflammation in the rat hippocampus. PLoS ONE 7:e45250. https://doi.org/10.1371/journal.pone.0045250
Chung WS, Welsh CA, Barres BA, Stevens B (2015) Do glia drive synaptic and cognitive impairment in disease? Nat Neurosci 18:1539–1545. https://doi.org/10.1038/nn.4142
Cibelli M et al (2010) Role of interleukin-1beta in postoperative cognitive dysfunction. Ann Neurol 68:360–368. https://doi.org/10.1002/ana.22082
Clarke LE, Liddelow SA, Chakraborty C, Munch AE, Heiman M, Barres BA (2018) Normal aging induces A1-like astrocyte reactivity. Proc Natl Acad Sci USA 115:E1896–E1905. https://doi.org/10.1073/pnas.1800165115
Cohen HY et al (2004) Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase. Science 305:390–392. https://doi.org/10.1126/science.1099196
Dallerac G, Rouach N (2016) Astrocytes as new targets to improve cognitive functions. Prog Neurobiol 144:48–67. https://doi.org/10.1016/j.pneurobio.2016.01.003
Davinelli S, Maes M, Corbi G, Zarrelli A, Willcox DC, Scapagnini G (2016) Dietary phytochemicals and neuro-inflammaging: from mechanistic insights to translational challenges. Immun Ageing 13:16. https://doi.org/10.1186/s12979-016-0070-3
Degos V et al (2013) Depletion of bone marrow-derived macrophages perturbs the innate immune response to surgery and reduces postoperative memory dysfunction. Anesthesiology 118:527–536. https://doi.org/10.1097/ALN.0b013e3182834d94
Deiner S et al (2017) intraoperative infusion of dexmedetomidine for prevention of postoperative delirium and cognitive dysfunction in elderly patients undergoing major elective noncardiac surgery: a randomized clinical trial. JAMA Surg 152:e171505. https://doi.org/10.1001/jamasurg.2017.1505
Di Benedetto S, Muller L, Wenger E, Duzel S, Pawelec G (2017) Contribution of neuroinflammation and immunity to brain aging and the mitigating effects of physical and cognitive interventions. Neurosci Biobehav Rev 75:114–128. https://doi.org/10.1016/j.neubiorev.2017.01.044
Duan X, Coburn M, Rossaint R, Sanders RD, Waesberghe JV, Kowark A (2018) Efficacy of perioperative dexmedetomidine on postoperative delirium: systematic review and meta-analysis with trial sequential analysis of randomised controlled trials. Br J Anaesth 121:384–397. https://doi.org/10.1016/j.bja.2018.04.046
Ellwardt E, Walsh JT, Kipnis J, Zipp F (2016) Understanding the role of T cells in CNS homeostasis. Trends Immunol 37:154–165. https://doi.org/10.1016/j.it.2015.12.008
Erdo F, Denes L, de Lange E (2017) Age-associated physiological and pathological changes at the blood–brain barrier: a review. J Cereb Blood Flow Metab 37:4–24. https://doi.org/10.1177/0271678X16679420
Evered L, Scott DA, Silbert B, Maruff P (2011) Postoperative cognitive dysfunction is independent of type of surgery and anesthetic. Anesth Analg 112:1179–1185. https://doi.org/10.1213/ANE.0b013e318215217e
Evered L et al (2018) Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018. Br J Anaesth 121:1005–1012. https://doi.org/10.1016/j.bja.2017.11.087
Feng X et al (2013) Surgery results in exaggerated and persistent cognitive decline in a rat model of the Metabolic Syndrome. Anesthesiology 118:1098–1105. https://doi.org/10.1097/ALN.0b013e318286d0c9
Feng X, Uchida Y, Koch L, Britton S, Hu J, Lutrin D, Maze M (2017) Exercise prevents enhanced postoperative neuroinflammation and cognitive decline and rectifies the gut microbiome in a rat model of metabolic syndrome. Front Immunol 8:1768. https://doi.org/10.3389/fimmu.2017.01768
Ferretti MT, Allard S, Partridge V, Ducatenzeiler A, Cuello AC (2012) Minocycline corrects early, pre-plaque neuroinflammation and inhibits BACE-1 in a transgenic model of Alzheimer’s disease-like amyloid pathology. J Neuroinflammation 9:62. https://doi.org/10.1186/1742-2094-9-62
Fontana L, Partridge L, Longo VD (2010) Extending healthy life span-from yeast to humans. Science 328:321–326. https://doi.org/10.1126/science.1172539
Forsberg A et al (2017) The immune response of the human brain to abdominal surgery. Ann Neurol 81:572–582. https://doi.org/10.1002/ana.24909
Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S4–9. https://doi.org/10.1093/gerona/glu057
Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G (2000) Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908:244–254
Fulop T, Le Page A, Fortin C, Witkowski JM, Dupuis G, Larbi A (2014) Cellular signaling in the aging immune system. Curr Opin Immunol 29:105–111. https://doi.org/10.1016/j.coi.2014.05.007
Gambus PL et al (2015) Relation between acute and long-term cognitive decline after surgery: influence of metabolic syndrome. Brain Behav Immun 50:203–208. https://doi.org/10.1016/j.bbi.2015.07.005
Gogenur I, Middleton B, Burgdorf S, Rasmussen LS, Skene DJ, Rosenberg J (2007) Impact of sleep and circadian disturbances in urinary 6-sulphatoxymelatonin levels, on cognitive function after major surgery. J Pineal Res 43:179–184. https://doi.org/10.1111/j.1600-079X.2007.00460.x
Gong M, Chen G, Zhang XM, Xu LH, Wang HM, Yan M (2012) Parecoxib mitigates spatial memory impairment induced by sevoflurane anesthesia in aged rats. Acta Anaesthesiol Scand 56:601–607. https://doi.org/10.1111/j.1399-6576.2012.02665.x
Grabert K et al (2016) Microglial brain region-dependent diversity and selective regional sensitivities to aging. Nat Neurosci 19:504–516. https://doi.org/10.1038/nn.4222
Grinan-Ferre C et al (2016) Behaviour and cognitive changes correlated with hippocampal neuroinflammaging and neuronal markers in female SAMP8, a model of accelerated senescence. Exp Gerontol 80:57–69. https://doi.org/10.1016/j.exger.2016.03.014
Hanning CD (2005) Postoperative cognitive dysfunction. Br J Anaesth 95:82–87. https://doi.org/10.1093/bja/aei062
Harry GJ (2013) Microglia during development and aging. Pharmacol Ther 139:313–326. https://doi.org/10.1016/j.pharmthera.2013.04.013
He HJ et al (2012) Surgery upregulates high mobility group box-1 and disrupts the blood–brain barrier causing cognitive dysfunction in aged rats. CNS Neurosci Ther 18:994–1002. https://doi.org/10.1111/cns.12018
Hillman CH, Erickson KI, Kramer AF (2008) Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci 9:58–65. https://doi.org/10.1038/nrn2298
Hovens IB, Schoemaker RG, van der Zee EA, Heineman E, Izaks GJ, van Leeuwen BL (2012) Thinking through postoperative cognitive dysfunction: how to bridge the gap between clinical and pre-clinical perspectives. Brain Behav Immun 26:1169–1179. https://doi.org/10.1016/j.bbi.2012.06.004
Hovens IB, Schoemaker RG, van der Zee EA, Absalom AR, Heineman E, van Leeuwen BL (2014) Postoperative cognitive dysfunction: involvement of neuroinflammation and neuronal functioning. Brain Behav Immun 38:202–210. https://doi.org/10.1016/j.bbi.2014.02.002
Hovens IB, van Leeuwen BL, Nyakas C, Heineman E, van der Zee EA, Schoemaker RG (2015) Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats. Neurobiol Learn Mem 118:74–79. https://doi.org/10.1016/j.nlm.2014.11.009
Hoy SM, Keating GM (2011) dexmedetomidine a review of its use for sedation in mechanically ventilated patients in an intensive care setting and for procedural sedation. Drugs 71:1481–1501. https://doi.org/10.2165/11207190-000000000-00000
Hu J, Feng X, Valdearcos M, Lutrin D, Uchida Y, Koliwad SK, Maze M (2018) Interleukin-6 is both necessary and sufficient to produce perioperative neurocognitive disorder in mice. Br J Anaesth 120:537–545. https://doi.org/10.1016/j.bja.2017.11.096
Huang C, Irwin MG, Wong GTC, Chang RCC (2018) Evidence of the impact of systemic inflammation on neuroinflammation from a non-bacterial endotoxin animal model. J Neuroinflammation 15:147. https://doi.org/10.1186/s12974-018-1163-z
Hughes CG et al (2017) Surgery and anesthesia exposure is not a risk factor for cognitive impairment after major noncardiac surgery and critical illness. Ann Surg 265:1126–1133. https://doi.org/10.1097/SLA.0000000000001885
Jalal FY, Yang Y, Thompson JF, Roitbak T, Rosenberg GA (2015) Hypoxia-induced neuroinflammatory white-matter injury reduced by minocycline in SHR/SP. J Cereb Blood Flow Metab 35:1145–1153. https://doi.org/10.1038/jcbfm.2015.21
Jiang Y et al (2018) Upregulation of TREM2 ameliorates neuroinflammatory responses and improves cognitive deficits triggered by surgical trauma in Appswe/PS1dE9 Mice. Cell Physiol Biochem 46:1398–1411. https://doi.org/10.1159/000489155
Jyothi HJ et al (2015) Aging causes morphological alterations in astrocytes and microglia in human substantia nigra pars compacta. Neurobiol Aging 36:3321–3333. https://doi.org/10.1016/j.neurobiolaging.2015.08.024
Kakuta H, Zheng X, Oda H, Harada S, Sugimoto Y, Sasaki K, Tai A (2008) Cyclooxygenase-1-selective inhibitors are attractive candidates for analgesics that do not cause gastric damage. Design and in vitro/in vivo evaluation of a benzamide-type cyclooxygenase-1 selective inhibitor. J Med Chem 51:2400–2411. https://doi.org/10.1021/jm701191z
Kawano T, Eguchi S, Iwata H, Tamura T, Kumagai N, Yokoyama M (2015) Impact of preoperative environmental enrichment on prevention of development of cognitive impairment following abdominal surgery in a rat model. Anesthesiology 123:160–170. https://doi.org/10.1097/ALN.0000000000000697
Kohama SG, Goss JR, Finch CE, McNeill TH (1995) Increases of glial fibrillary acidic protein in the aging female mouse brain. Neurobiol Aging 16:59–67. https://doi.org/10.1016/0197-4580(95)80008-F
Kong F, Chen S, Cheng Y, Ma L, Lu H, Zhang H, Hu W (2013) Minocycline attenuates cognitive impairment induced by isoflurane anesthesia in aged rats. PLoS ONE 8:e61385. https://doi.org/10.1371/journal.pone.0061385
Kong FJ, Ma LL, Zhang HH, Zhou JQ (2015) Alpha 7 nicotinic acetylcholine receptor agonist GTS-21 mitigates isoflurane-induced cognitive impairment in aged rats. J Surg Res 194:255–261. https://doi.org/10.1016/j.jss.2014.09.043
Kubota K et al (2018) Age is the most significantly associated risk factor with the development of delirium in patients hospitalized for more than 5 days in surgical wards: retrospective cohort study. Ann Surg 267:874–877. https://doi.org/10.1097/SLA.0000000000002347
Lana D, Iovino L, Nosi D, Wenk GL, Giovannini MG (2016) The neuron-astrocyte-microglia triad involvement in neuroinflammaging mechanisms in the CA3 hippocampus of memory-impaired aged rats. Exp Gerontol 83:71–88. https://doi.org/10.1016/j.exger.2016.07.011
Le V et al (2016) Premedication with intravenous ibuprofen improves recovery characteristics and stress response in adults undergoing laparoscopic cholecystectomy: a randomized controlled trial. Pain Med. https://doi.org/10.1093/pm/pnv113
Li Q, Barres BA (2017) Microglia and macrophages in brain homeostasis and disease. Nat Rev Immunol. https://doi.org/10.1038/nri.2017.125
Li SY, Xia LX, Zhao YL, Yang L, Chen YL, Wang JT, Luo AL (2013) Minocycline mitigates isoflurane-induced cognitive impairment in aged rats. Brain Res 1496:84–93. https://doi.org/10.1016/j.brainres.2012.12.025
Li XM, Zhou MT, Wang XM, Ji MH, Zhou ZQ, Yang JJ (2014) Resveratrol pretreatment attenuates the isoflurane-induced cognitive impairment through its anti-inflammation and -apoptosis actions in aged mice. J Mol Neurosci 52:286–293. https://doi.org/10.1007/s12031-013-0141-2
Li Y et al (2016a) Deferoxamine regulates neuroinflammation and iron homeostasis in a mouse model of postoperative cognitive dysfunction. J Neuroinflammation 13:268. https://doi.org/10.1186/s12974-016-0740-2
Li Z et al (2016b) Surgery-induced hippocampal angiotensin II elevation causes blood–brain barrier disruption via MMP/TIMP in aged rats. Front Cell Neurosci 10:105. https://doi.org/10.3389/fncel.2016.00105
Liang Z et al (2017) Impact of aging immune system on neurodegeneration and potential immunotherapies. Prog Neurobiol 157:2–28. https://doi.org/10.1016/j.pneurobio.2017.07.006
Liddelow SA et al (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541:481–487. https://doi.org/10.1038/nature21029
Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194–1217. https://doi.org/10.1016/j.cell.2013.05.039
Louveau A, Harris TH, Kipnis J (2015a) Revisiting the mechanisms of CNS immune privilege. Trends Immunol 36:569–577. https://doi.org/10.1016/j.it.2015.08.006
Louveau A et al (2015b) Structural and functional features of central nervous system lymphatic vessels. Nature 523:337–341. https://doi.org/10.1038/nature14432
Louveau A, Plog BA, Antila S, Alitalo K, Nedergaard M, Kipnis J (2017) Understanding the functions and relationships of the glymphatic system and meningeal lymphatics. J Clin Invest 127:3210–3219. https://doi.org/10.1172/JCI90603
Lv ZT, Huang JM, Zhang JM, Zhang JM, Guo JF, Chen AM (2016) Effect of ulinastatin in the treatment of postoperative cognitive dysfunction: review of current literature. Biomed Res Int 2016:2571080. https://doi.org/10.1155/2016/2571080
Ma Y, Cheng Q, Wang E, Li L, Zhang X (2015) Inhibiting tumor necrosis factor-alpha signaling attenuates postoperative cognitive dysfunction in aged rats. Mol Med Rep 12:3095–3100. https://doi.org/10.3892/mmr.2015.3744
Moller JT et al (1998) Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International study of post-operative cognitive dysfunction. Lancet 351:857–861
Monk TG, Weldon BC, Garvan CW, Dede DE, van der Aa MT, Heilman KM, Gravenstein JS (2008) Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology 108:18–30. https://doi.org/10.1097/01.anes.0000296071.19434.1e
Montagne A et al (2015) Blood–brain barrier breakdown in the aging human hippocampus. Neuron 85:296–302. https://doi.org/10.1016/j.neuron.2014.12.032
Newfield P (2009) Postoperative cognitive dysfunction. Med Rep 1:14. https://doi.org/10.3410/m1-14
Ni P, Dong H, Wang Y, Zhou Q, Xu M, Qian Y, Sun J (2018) IL-17A contributes to perioperative neurocognitive disorders through blood–brain barrier disruption in aged mice. J Neuroinflammation 15:332. https://doi.org/10.1186/s12974-018-1374-3
Norden DM, Godbout JP (2013) Review: microglia of the aged brain: primed to be activated and resistant to regulation. Neuropathol Appl Neurobiol 39:19–34. https://doi.org/10.1111/j.1365-2990.2012.01306.x
Paeschke N, von Haefen C, Endesfelder S, Sifringer M, Spies CD (2017) Dexmedetomidine prevents lipopolysaccharide-induced microRNA expression in the adult rat brain. Int J Mol Sci. https://doi.org/10.3390/ijms18091830
Pan K, Li X, Chen Y, Zhu D, Li Y, Tao G, Zuo Z (2016) Deferoxamine pre-treatment protects against postoperative cognitive dysfunction of aged rats by depressing microglial activation via ameliorating iron accumulation in hippocampus. Neuropharmacology 111:180–194. https://doi.org/10.1016/j.neuropharm.2016.09.004
Peng M, Wang YL, Wang FF, Chen C, Wang CY (2012) The cyclooxygenase-2 inhibitor parecoxib inhibits surgery-induced proinflammatory cytokine expression in the hippocampus in aged rats. J Surg Res 178:e1–8. https://doi.org/10.1016/j.jss.2012.08.030
Perea G, Navarrete M, Araque A (2009) Tripartite synapses: astrocytes process and control synaptic information. Trends Neurosci 32:421–431. https://doi.org/10.1016/j.tins.2009.05.001
Pizza V, Agresta A, D’Acunto CW, Festa M, Capasso A (2011) Neuroinflamm-aging and neurodegenerative diseases: an overview. CNS Neurol Disord 10:621–634
Qiu LL et al (2016) NADPH oxidase 2-derived reactive oxygen species in the hippocampus might contribute to microglial activation in postoperative cognitive dysfunction in aged mice. Brain Behav Immun 51:109–118. https://doi.org/10.1016/j.bbi.2015.08.002
Rawji KS, Mishra MK, Michaels NJ, Rivest S, Stys PK, Yong VW (2016) Immunosenescence of microglia and macrophages: impact on the ageing central nervous system. Brain 139:653–661. https://doi.org/10.1093/brain/awv395
Rosczyk HA, Sparkman NL, Johnson RW (2008) Neuroinflammation and cognitive function in aged mice following minor surgery. Exp Gerontol 43:840–846. https://doi.org/10.1016/j.exger.2008.06.004
Salter MW, Stevens B (2017) Microglia emerge as central players in brain disease. Nat Med 23:1018–1027. https://doi.org/10.1038/nm.4397
Sampson TR et al (2016) Gut microbiota regulate motor deficits and neuroinflammation in a model of parkinson’s disease. Cell 167(1469–1480):e1412. https://doi.org/10.1016/j.cell.2016.11.018
Schloesser RJ, Lehmann M, Martinowich K, Manji HK, Herkenham M (2010) Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress. Mol Psychiatry 15:1152–1163. https://doi.org/10.1038/mp.2010.34
Schuitemaker A et al (2012) Microglial activation in healthy aging. Neurobiol Aging 33:1067–1072. https://doi.org/10.1016/j.neurobiolaging.2010.09.016
Schwartz M, Kipnis J, Rivest S, Prat A (2013) How do immune cells support and shape the brain in health, disease, and aging? J Neurosci 33:17587–17596. https://doi.org/10.1523/JNEUROSCI.3241-13.2013
Skvarc DR et al (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.2017.11.011
Sochocka M, Diniz BS, Leszek J (2017) Inflammatory response in the CNS: friend or foe? Mol Neurobiol 54:8071–8089. https://doi.org/10.1007/s12035-016-0297-1
Sofroniew MV (2014) Astrogliosis. Cold Spring Harb Perspect Biol 7:a020420. https://doi.org/10.1101/cshperspect.a020420
Sofroniew MV, Vinters HV (2010) Astrocytes: biology and pathology. Acta Neuropathol 119:7–35. https://doi.org/10.1007/s00401-009-0619-8
Soreq L et al (2017) Major shifts in glial regional identity are a transcriptional hallmark of human brain aging. Cell Rep 18:557–570. https://doi.org/10.1016/j.celrep.2016.12.011
Sprung J et al (2017) Postoperative delirium in elderly patients is associated with subsequent cognitive impairment. Br J Anaesth 119:316–323. https://doi.org/10.1093/bja/aex130
Steinmetz J, Christensen KB, Lund T, Lohse N, Rasmussen LS, Group I (2009) Long-term consequences of postoperative cognitive dysfunction. Anesthesiology 110:548–555. https://doi.org/10.1097/ALN.0b013e318195b569
Stogsdill JA et al (2017) Astrocytic neuroligins control astrocyte morphogenesis and synaptogenesis. Nature 551:192–197. https://doi.org/10.1038/nature24638
Stollings LM, Jia LJ, Tang P, Dou H, Lu B, Xu Y (2016) Immune modulation by volatile anesthetics. Anesthesiology 125:399–411. https://doi.org/10.1097/ALN.0000000000001195
Su X et al (2016) Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet 388:1893–1902. https://doi.org/10.1016/S0140-6736(16)30580-3
Sun L, Dong R, Xu X, Yang X, Peng M (2017) Activation of cannabinoid receptor type 2 attenuates surgery-induced cognitive impairment in mice through anti-inflammatory activity. J Neuroinflammation 14:138. https://doi.org/10.1186/s12974-017-0913-7
Tchkonia T, Kirkland JL (2018) Aging, cell senescence, and chronic disease: emerging therapeutic strategies. JAMA. https://doi.org/10.1001/jama.2018.12440
Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M, Maze M (2010) Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci USA 107:20518–20522. https://doi.org/10.1073/pnas.1014557107
Terrando N et al (2011) Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol 70:986–995. https://doi.org/10.1002/ana.22664
Terrando N, Eriksson LI, Eckenhoff RG (2015a) Perioperative neurotoxicity in the elderly: summary of the 4th International Workshop. Anesth Analg 120:649–652. https://doi.org/10.1213/ANE.0000000000000624
Terrando N et al (2015b) Stimulation of the alpha7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice. Mol Med (Cambridge, Mass) 20:667–675. https://doi.org/10.2119/molmed.2014.00143
Terrando N et al (2016) Systemic HMGB1 o. Front Immunol 7:441. https://doi.org/10.3389/fimmu.2016.00441
Thion MS et al (2018) Microbiome influences prenatal and adult microglia in a sex-specific manner. Cell 172(500–516):e516. https://doi.org/10.1016/j.cell.2017.11.042
Trivino-Paredes J, Patten AR, Gil-Mohapel J, Christie BR (2016) The effects of hormones and physical exercise on hippocampal structural plasticity. Front Neuroendocrinol 41:23–43. https://doi.org/10.1016/j.yfrne.2016.03.001
Vacas S, Degos V, Feng X, Maze M (2013) The neuroinflammatory response of postoperative cognitive decline. Br Med Bull 106:161–178. https://doi.org/10.1093/bmb/ldt006
Vacas S, Degos V, Tracey KJ, Maze M (2014) High-mobility group box 1 protein initiates postoperative cognitive decline by engaging bone marrow-derived macrophages. Anesthesiology 120:1160–1167. https://doi.org/10.1097/ALN.0000000000000045
Vacas S, Degos V, Maze M (2017) Fragmented sleep enhances postoperative neuroinflammation but not cognitive dysfunction. Anesth Analg 124:270–276. https://doi.org/10.1213/ANE.0000000000001675
Vaiserman AM, Koliada AK, Marotta F (2017) Gut microbiota: a player in aging and a target for anti-aging intervention. Ageing Res Rev 35:36–45. https://doi.org/10.1016/j.arr.2017.01.001
van de Haar HJ, Burgmans S, Hofman PA, Verhey FR, Jansen JF, Backes WH (2015) Blood–brain barrier impairment in dementia: current and future in vivo assessments. Neurosci Biobehav Rev 49:71–81. https://doi.org/10.1016/j.neubiorev.2014.11.022
Vasto S et al (2007) Inflammatory networks in ageing, age-related diseases and longevity. Mech Ageing Dev 128:83–91. https://doi.org/10.1016/j.mad.2006.11.015
Vincent JA, Mohr S (2007) Inhibition of caspase-1/interleukin-1β signaling prevents degeneration of retinal capillaries in diabetes and galactosemia. Diabetes 56:224–230. https://doi.org/10.2337/db06-0427
Wan Y, Xu J, Ma D, Zeng Y, Cibelli M, Maze M (2007) Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology 106:436–443
Wan Y et al (2010) Cognitive decline following major surgery is associated with gliosis, beta-amyloid accumulation, and tau phosphorylation in old mice. Crit Care Med 38:2190–2198. https://doi.org/10.1097/CCM.0b013e3181f17bcb
Wang B et al (2017a) Blood–brain barrier disruption leads to postoperative cognitive dysfunction. Curr Neurovasc Res 14:359–367. https://doi.org/10.2174/1567202614666171009105825
Wang KY, Yang QY, Tang P, Li HX, Zhao HW, Ren XB (2017b) Effects of ulinastatin on early postoperative cognitive function after one-lung ventilation surgery in elderly patients receiving neoadjuvant chemotherapy. Metab Brain Dis 32:427–435. https://doi.org/10.1007/s11011-016-9926-7
Wang Z, Meng S, Cao L, Chen Y, Zuo Z, Peng S (2018) Critical role of NLRP3-caspase-1 pathway in age-dependent isoflurane-induced microglial inflammatory response and cognitive impairment. J Neuroinflammation 15:109. https://doi.org/10.1186/s12974-018-1137-1
Wu X et al (2017) Curcumin attenuates surgery-induced cognitive dysfunction in aged mice. Metab Brain Dis 32:789–798. https://doi.org/10.1007/s11011-017-9970-y
Xiong C, Liu J, Lin D, Zhang J, Terrando N, Wu A (2018) Complement activation contributes to perioperative neurocognitive disorders in mice. J Neuroinflammation 15:254. https://doi.org/10.1186/s12974-018-1292-4
Xu Z et al (2014) Age-dependent postoperative cognitive impairment and Alzheimer-related neuropathology in mice. Sci Rep 4:3766. https://doi.org/10.1038/srep03766
Xu J, Dong H, Qian Q, Zhang X, Wang Y, Jin W, Qian Y (2017) Astrocyte-derived CCL2 participates in surgery-induced cognitive dysfunction and neuroinflammation via evoking microglia activation. Behav Brain Res 332:145–153. https://doi.org/10.1016/j.bbr.2017.05.066
Yang S et al (2017) Anesthesia and surgery impair blood–brain barrier and cognitive function in mice. Front Immunol 8:902. https://doi.org/10.3389/fimmu.2017.00902
Ye JS, Chen L, Lu YY, Lei SQ, Peng M, Xia ZY (2018) SIRT3 activator honokiol ameliorates surgery/anesthesia-induced cognitive decline in mice through anti-oxidative stress and anti-inflammatory in hippocampus. CNS Neurosci Ther. https://doi.org/10.1111/cns.13053
Yin JA et al (2017) Genetic variation in glia-neuron signalling modulates ageing rate. Nature 551:198–203. https://doi.org/10.1038/nature24463
Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J (1999) A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci USA 96:13496–13500. https://doi.org/10.1073/pnas.96.23.13496
Zhan G et al (2018) Abnormal gut microbiota composition contributes to cognitive dysfunction in SAMP8 mice. Aging 10:1257–1267. https://doi.org/10.18632/aging.101464
Zhang X, Yao H, Qian Q, Li N, Jin W, Qian Y (2016) Cerebral mast cells participate in postoperative cognitive dysfunction by promoting astrocyte activation. Cell Physiol Biochem 40:104–116. https://doi.org/10.1159/000452528
Zhang DF et al (2018) Impact of dexmedetomidine on long-term outcomes after noncardiac surgery in elderly: 3-year follow-up of a randomized controlled trial. Ann Surg. https://doi.org/10.1097/sla.0000000000002801
Zhao Y et al (2016) Neuroinflammation induced by surgery does not impair the reference memory of young adult mice. Mediat Inflamm 2016:3271579. https://doi.org/10.1155/2016/3271579
Zhao WX et al (2017) Acetaminophen attenuates lipopolysaccharide-induced cognitive impairment through antioxidant activity. J Neuroinflammation 14:17. https://doi.org/10.1186/s12974-016-0781-6
Zheng B, Lai R, Li J, Zuo Z (2017) Critical role of P2X7 receptors in the neuroinflammation and cognitive dysfunction after surgery. Brain Behav Immun 61:365–374. https://doi.org/10.1016/j.bbi.2017.01.005
Zhu YJ, Peng K, Meng XW, Ji FH (2016a) Attenuation of neuroinflammation by dexmedetomidine is associated with activation of a cholinergic anti-inflammatory pathway in a rat tibial fracture model. Brain Res 1644:1–8. https://doi.org/10.1016/j.brainres.2016.04.074
Zhu YZ, Yao R, Zhang Z, Xu H, Wang LW (2016b) Parecoxib prevents early postoperative cognitive dysfunction in elderly patients undergoing total knee arthroplasty: a double-blind, randomized clinical consort study. Medicine 95:e4082. https://doi.org/10.1097/md.0000000000004082
Zhu H, Liu W, Fang H (2018) Inflammation caused by peripheral immune cells across into injured mouse blood brain barrier can worsen postoperative cognitive dysfunction induced by isoflurane. BMC Cell Biol 19:23. https://doi.org/10.1186/s12860-018-0172-1
Zlokovic BV (2008) The blood–brain barrier in health and chronic neurodegenerative disorders. Neuron 57:178–201. https://doi.org/10.1016/j.neuron.2008.01.003
Acknowledgements
The present work was supported by grants from the National Natural Science Foundation of China (Grant No. 81400882 to Shiyong Li, Grant Nos. 81771159, 81571047 and 81271233 to Ailin Luo, Grant No. 8150051085 to Yilin Zhao), Science and Technology Projects of Wuhan (Grant Number 2015060101010036 to Ailin Luo) and also supported by 2010 Clinical Key Disciplines Construction Grant from the Ministry of Health of China (Grant to Anesthesiology Disciplines of Tongji medical college).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflicts of interest to disclose.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Luo, A., Yan, J., Tang, X. et al. Postoperative cognitive dysfunction in the aged: the collision of neuroinflammaging with perioperative neuroinflammation. Inflammopharmacol 27, 27–37 (2019). https://doi.org/10.1007/s10787-018-00559-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10787-018-00559-0