Culley, DJ, Baxter, MG, Crosby, CA, Yukhananov, R, Crosby, G. Impaired acquisition of spatial memory 2 weeks after isoflurane and isoflurane-nitrous oxide anesthesia in aged rats. Anesth Analg 2004; 99: 1393–7Google Scholar

Rosczyk, H, Sparkman, NL, Johnson, R. Neuroinflammation and cognitive function in aged mice following minor surgery. Exp Gerontol 2008; 43: 840–6Google Scholar

Terrando, N, Monaco, C, Ma, D, Foxwell, BM, Feldmann, M, Maze, M. Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci USA 2010; 107: 20518–22Google Scholar

Barrientos, RM, Hein, AM, Frank, MG, Watkins, LR, Maier, SF. Intracisternal interleukin-1 receptor antagonist prevents postoperative cognitive decline and neuroinflammatory response in aged rats. J Neurosci 2012; 32: 14641–8Google Scholar

Degos, V, Vacas, S, Han, Z, et al. Depletion of bone marrow-derived macrophages perturbs the innate immune response to surgery and reduces postoperative memory dysfunction. Anesthesiology 2013; 118: 527–36Google Scholar

Terrando, N, Eriksson, LI, Ryu, JK, et al. Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol 2011; 70: 986–95Google Scholar

Hovens, IB, Schoemaker, RG, van der Zee, EA, Absalom, AR, Heineman, E, van Leeuwen, BL. Postoperative cognitive dysfunction: involvement of neuroinflammation and neuronal functioning. Brain Behav Immun 2014; 38: 202–10Google Scholar

Xu, Z, Dong, Y, Wang, H, et al. Age-dependent postoperative cognitive impairment and Alzheimer-related neuropathology in mice. Sci Rep 2014; 4: 3766Google Scholar

Wan, Y, Xu, J, Meng, F, et al. Cognitive decline following major surgery is associated with gliosis, beta-amyloid accumulation, and tau phosphorylation in old mice. Crit Care Med 2010; 38: 2190–8Google Scholar

Le, Y, Liu, S, Peng, M, et al. Aging differentially affects the loss of neuronal dendritic spine, neuroinflammation and memory impairment at rats after surgery. PLoS One 2014; 9: e106837Google Scholar

Xie, P, Yu, T, Fu, X, et al. Altered functional connectivity in an aged rat model of postoperative cognitive dysfunction: a study using resting-state functional MRI. PLoS One 2013; 8: e64820Google Scholar

Chen, C, Cai, J, Zhang, S, et al. Protective effect of RNase on unilateral nephrectomy-induced postoperative cognitive dysfunction in aged mice. PLoS One 2015; 10: e0134307Google Scholar

Tang, JX, Mardini, F, Janik, LS, et al. Modulation of murine Alzheimer pathogenesis and behavior by surgery. Ann Surg 2013; 257: 439–48Google Scholar

Mardini, F, Tang, JX, Li, JC, Arroliga, MJ, Eckenhoff, RG, Eckenhoff, MF. Effects of propofol and surgery on neuropathology and cognition in the 3xTgAD Alzheimer transgenic mouse model. Br J Anaesth 2017; 119: 472–80Google Scholar

Skelly, DT, Griffin, ÉW, Murray, CL, Harney, S, O’Boyle, C, Hennessy, E, et al. Acute transient cognitive dysfunction and acute brain injury induced by systemic inflammation occur by dissociable IL-1-dependent mechanisms. Mol Psychiatry 2018; doi: 10.1038/s41380-018-0075-8 [Epub ahead of print]Google Scholar

Iwashyna, TJ, Ely, EW, Smith, DM, Langa, KM. Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 2010; 304: 1787–94Google Scholar

Widmann, CN, Heneka, MT. Long-term cerebral consequences of sepsis. Lancet Neurol 2014; 13: 630–6Google Scholar

Schwalm, MT, Pasquali, M, Miguel, SP, et al. Acute brain inflammation and oxidative damage are related to long-term cognitive deficits and markers of neurodegeneration in sepsis-survivor rats. Mol Neurobiol 2014; 49: 380–5Google Scholar

Biff, D, Petronilho, F, Constantino, L, et al. Correlation of acute phase inflammatory and oxidative markers with long-term cognitive impairment in sepsis survivors rats. Shock 2013; 40: 45–8Google Scholar

Semmler, A, Frisch, C, Debeir, T, et al. Long-term cognitive impairment, neuronal loss and reduced cortical cholinergic innervation after recovery from sepsis in a rodent model. Exp Neurol 2007; 204: 733–40Google Scholar

Eckenhoff, RG, Laudansky, KF. Anesthesia, surgery, illness and Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 2013; 47: 162–6Google Scholar

Murphy, TE, Han, L, Allore, HG, Peduzzi, PN, Gill, TM, Lin, H. Treatment of death in the analysis of longitudinal studies of gerontological outcomes. J Gerontol A Biol Sci Med Sci 2011; 66: 109–14Google Scholar

Fu, HQ, Yang, T, Xiao, W, et al. Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats. PLoS One 2014; 9: e106331Google Scholar

Terrando, N, Rei Fidalgo, A, Vizcaychipi, M, et al. The impact of IL-1 modulation on the development of lipopolysaccharide-induced cognitive dysfunction. Crit Care 2010; 14: R88Google Scholar

Sun, J, Zhang, S, Zhang, X, Zhang, X, Dong, H, Qian, Y. IL-17A is implicated in lipopolysaccharide-induced neuroinflammation and cognitive impairment in aged rats via microglial activation. J Neuroinflammation 2015; 12: 165Google Scholar

Barrientos, RM, Frank, MG, Hein, AM, et al. Time course of hippocampal IL-1 beta and memory consolidation impairments in aging rats following peripheral infection. Brain Behav Immun 2009; 23: 46–54Google Scholar

Cunningham, C, Sanderson, DJ. Malaise in the water maze: untangling the effects of LPS and IL-1 beta on learning and memory. Brain Behav Immun 2008; 22: 1117–27Google Scholar

Tang, JX, Mardini, F, Caltagarone, BM, et al. Anesthesia in presymptomatic Alzheimer’s disease: a study using the triple-transgenic mouse model. Alzheimers Dement 2011; 7: 521–31Google Scholar

Hovens, IB, Schoemaker, RG, van der Zee, EA, Heineman, E, Nyakas, C, van Leeuwen, BL. Surgery-induced behavioral changes in aged rats. Exp Gerontol 2013; 48: 1204–11Google Scholar

Murray, C, Sanderson, DJ, Barkus, C, et al. Systemic inflammation induces acute working memory deficits in the primed brain: relevance for delirium. Neurobiol Aging 2012; 33: 603–16.e3Google Scholar

Davis, DH, Skelly, DT, Murray, C, et al. Worsening cognitive impairment and neurodegenerative pathology progressively increase risk for delirium. Am J Geriatr Psychiatry 2015; 23: 403–15Google Scholar

Cunningham, C, Campion, S, Lunnon, K, et al. Systemic inflammation induces acute behavioral and cognitive changes and accelerates neurodegenerative disease. Biol Psychiatry 2009; 65: 304–12Google Scholar

Lu, SM, Gui, B, Dong, HQ, et al. Prophylactic lithium alleviates splenectomy-induced cognitive dysfunction possibly by inhibiting hippocampal TLR4 activation in aged rats. Brain Res Bull 2015; 114: 31–41Google Scholar

Hovens, IB, van Leeuwen, BL, Nyakas, C, Heineman, E, van der Zee, EA, Schoemaker, RG. Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats. Neurobiol Learn Mem 2015; 118: 74–9Google Scholar

Barrientos, RM, Higgins, EA, Biedenkapp, JC, et al. Peripheral infection and aging interact to impair hippocampal memory consolidation. Neurobiol Aging 2006; 27: 723–32Google Scholar

Chen, G, Chen, KS, Knox, J, et al. A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer’s disease. Nature 2000; 408: 975–9Google Scholar

Ren, Q, Peng, M, Dong, Y, et al. Surgery plus anesthesia induces loss of attention in mice. Front Cell Neurosci 2015; 9: 346Google Scholar

Zhang, J, Tan, H, Jiang, W, Zuo, Z. The choice of general anesthetics may not affect neuroinflammation and impairment of learning and memory after surgery in elderly rats. J Neuroimmune Pharmacol 2015; 10: 179–89Google Scholar

Qian, XL, Zhang, W, Liu, MZ, et al. Dexmedetomidine improves early postoperative cognitive dysfunction in aged mice. Eur J Pharmacol 2015; 746: 206–12Google Scholar

Culley, DJ, Snayd, M, Baxter, MG, et al. Systemic inflammation impairs attention and cognitive flexibility but not associative learning in aged rats: possible implications for delirium. Front Aging Neurosci 2014; 6: 107Google Scholar

Kilkenny, C, Browne, WJ, Cuthill, IC, Emerson, M, Altman, DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 2010; 8: e1000412Google Scholar

Cao, XZ, Ma, H, Wang, JK, et al. Postoperative cognitive deficits and neuroinflammation in the hippocampus triggered by surgical trauma are exacerbated in aged rats. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 1426–32Google Scholar

Wuri, G, Wang, DX, Zhou, Y, Zhu, SN. Effects of surgical stress on long-term memory function in mice of different ages. Acta Anaesthesiol Scand 2011; 55: 474–85Google Scholar

He, HJ, Wang, Y, Le, Y, et al. Surgery upregulates high mobility group box-1 and disrupts the blood-brain barrier causing cognitive dysfunction in aged rats. CNS Neurosci Ther 2012; 18: 994–1002Google Scholar

Feng, X, Degos, V, Koch, LG, et al. Surgery results in exaggerated and persistent cognitive decline in a rat model of the metabolic syndrome. Anesthesiology 2013; 118: 1098–105Google Scholar

Li, M, Yong-Zhe, L, Ya-Qun, M, Sheng-Suo, Z, Li-Tao, Z, Ning-Ling, P. Ulinastatin alleviates neuroinflammation but fails to improve cognitive function in aged rats following partial hepatectomy. Neurochem Res 2013; 38: 1070–7Google Scholar

Li, RL, Zhang, ZZ, Peng, M, et al. Postoperative impairment of cognitive function in old mice: a possible role for neuroinflammation mediated by HMGB1, S100B, and RAGE. J Surg Res 2013; 185: 815–24Google Scholar

Su, X, Feng, X, Terrando, N, et al. Dysfunction of inflammation-resolving pathways is associated with exaggerated postoperative cognitive decline in a rat model of the metabolic syndrome. Mol Med 2013; 18: 1481–90Google Scholar

Bi, Y, Liu, S, Yu, X, Wang, M, Wang, Y. Adaptive and regulatory mechanisms in aged rats with postoperative cognitive dysfunction. Neural Regen Res 2014; 9: 534–9Google Scholar

Jin, WJ, Feng, SW, Feng, Z, Lu, SM, Qi, T, Qian, YN. Minocycline improves postoperative cognitive impairment in aged mice by inhibiting astrocytic activation. Neuroreport 2013; 25: 1–6Google Scholar

Kawano, T, Takahashi, T, Iwata, H, et al. Effects of ketoprofen for prevention of postoperative cognitive dysfunction in aged rats. J Anesth 2014; 28: 932–6Google Scholar

Li, Z, Cao, Y, Li, L, et al. Prophylactic angiotensin type 1 receptor antagonism confers neuroprotection in an aged rat model of postoperative cognitive dysfunction. Biochem Biophys Res Commun 2014; 449: 74–80Google Scholar

Gambus, PL, Troconiz, IF, Feng, X, et al. Relation between acute and long-term cognitive decline after surgery: influence of metabolic syndrome. Brain Behav Immun 2015; 50: 203–8Google Scholar

Hovens, IB, van Leeuwen, BL, Nyakas, C, Heineman, E, van der Zee, EA, Schoemaker, RG. Prior infection exacerbates postoperative cognitive dysfunction in aged rats. Am J Physiol Regul Integr Comp Physiol 2015; 309: R148–59Google Scholar

Jia, M, Liu, WX, Sun, HL, et al. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, attenuates postoperative cognitive dysfunction in aging mice. Front Mol Neurosci 2015; 8: 52Google Scholar

Kawano, T, Eguchi, S, Iwata, H, Tamura, T, Kumagai, N, Yokoyama, M. Impact of preoperative environmental enrichment on prevention of development of cognitive impairment following abdominal surgery in a rat model. Anesthesiology 2015; 123: 160–70Google Scholar

Li, Y, Wang, S, Ran, K, Hu, Z, Liu, Z, Duan, K. Differential hippocampal protein expression between normal aged rats and aged rats with postoperative cognitive dysfunction: a proteomic analysis. Mol Med Rep 2015; 12: 2953–60Google Scholar

Liu, Y, Ma, L, Jiao, L, et al. Mammalian target of rapamycin/p70 ribosomal S6 protein kinase signaling is altered by sevoflurane and/or surgery in aged rats. Mol Med Rep 2015; 12: 8253–60Google Scholar

Ma, Y, Cheng, Q, Wang, E, Li, L, Zhang, X. Inhibiting tumor necrosis factor-alpha signaling attenuates postoperative cognitive dysfunction in aged rats. Mol Med Rep 2015; 12: 3095–100Google Scholar

Qiu, LL, Ji, MH, Zhang, H, et al. 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 2015; 51: 109–18Google Scholar

Tian, A, Ma, H, Zhang, R, et al. Interleukin17A promotes postoperative cognitive dysfunction by triggering β-amyloid accumulation via the transforming growth factor-β (TGFβ)/smad signaling pathway. PLoS One 2015; 10: e0141596Google Scholar

Tian, XS, Tong, YW, Li, ZQ, et al. Surgical stress induces brain-derived neurotrophic factor reduction and postoperative cognitive dysfunction via glucocorticoid receptor phosphorylation in aged mice. CNS Neurosci Ther 2015; 21: 398–409Google Scholar

Wang, HL, Ma, RH, Fang, H, Xue, ZG, Liao, QW. Impaired spatial learning memory after isoflurane anesthesia or appendectomy in aged mice is associated with microglia activation. J Cell Death 2015; 8: 9–19Google Scholar

Kawano, T, Iwata, H, Aoyama, B, et al. The role of hippocampal insulin signaling on postoperative cognitive dysfunction in an aged rat model of abdominal surgery. Life Sci 2016; 162: 87–94Google Scholar

Kawano, T, Eguchi, S, Iwata, H, et al. Pregabalin can prevent, but not treat, cognitive dysfunction following abdominal surgery in aged rats. Life Sci 2016; 148: 211–19Google Scholar

Li, Y, Pan, K, Chen, L, et al. Deferoxamine regulates neuroinflammation and iron homeostasis in a mouse model of postoperative cognitive dysfunction. J Neuroinflammation 2016; 13: 268Google Scholar

Pan, K, Li, X, Chen, Y, et al. Deferoxamine pre-treatment protects against postoperative cognitive dysfunction of aged rats by depressing microglial activation via ameliorating iron accumulation in hippocampus. Neuropharmacology 2016; 111: 180–94Google Scholar

Terrando, N, Yang, T, Wang, X, et al. Systemic HMGB1 neutralization prevents postoperative neurocognitive dysfunction in aged rats. Front Immunol 2016; 7: 441Google Scholar

Xiong, B, Shi, Q, Fang, H. Dexmedetomidine alleviates postoperative cognitive dysfunction by inhibiting neuron excitation in aged rats. Am J Transl Res 2016; 8: 70–80Google Scholar

Zhang, Z, Li, X, Li, F, An, L. Berberine alleviates postoperative cognitive dysfunction by suppressing neuroinflammation in aged mice. Int Immunopharmacol 2016; 38: 426–33Google Scholar

Feng, X, Uchida, Y, Koch, L, et al. Exercise prevents enhanced postoperative neuroinflammation and cognitive decline and rectifies the gut microbiome in a rat model of metabolic syndrome. Front Immunol 2017; 8: 1768Google Scholar

Feng, PP, Deng, P, Liu, LH, et al. Electroacupuncture alleviates postoperative cognitive dysfunction in aged rats by inhibiting hippocampal neuroinflammation activated via microglia/TLRs pathway. Evid Based Complement Alternat Med 2017; 2017: 6421260Google Scholar

Li, Z, Liu, F, Ma, H, et al. Age exacerbates surgery-induced cognitive impairment and neuroinflammation in Sprague-Dawley rats: the role of IL-4. Brain Res 2017; 1665: 65–73Google Scholar

Liu, PR, Zhou, Y, Zhang, Y, Diao, S. Electroacupuncture alleviates surgery-induced cognitive dysfunction by increasing alpha7-nAChR expression and inhibiting inflammatory pathway in aged rats. Neurosci Lett 2017; 659: 1–6Google Scholar

Miao, H, Dong, Y, Zhang, Y, et al. Anesthetic isoflurane or desflurane plus surgery differently affects cognitive function in Alzheimer's disease transgenic mice. Mol Neurobiol 2017; 55: 5623–38Google Scholar

Qi, Z, Tianbao, Y, Yanan, L, Xi, X, Jinhua, H, Qiujun, W. Pre-treatment with nimodipine and 7.5% hypertonic saline protects aged rats against postoperative cognitive dysfunction via inhibiting hippocampal neuronal apoptosis. Behav Brain Res 2017; 321: 1–7Google Scholar

Tian, A, Ma, H, Zhang, R, Cui, Y, Wan, C. Edaravone improves spatial memory and modulates endoplasmic reticulum stress-mediated apoptosis after abdominal surgery in mice. Exp Ther Med 2017; 14: 355–60Google Scholar

Tian, Y, Guo, S, Zhang, Y, Xu, Y, Zhao, P, Zhao, X. Effects of hydrogen-rich saline on hepatectomy-induced postoperative cognitive dysfunction in old mice. Mol Neurobiol 2017; 54: 2579–84Google Scholar

Wang, W, Zhang, XY, Feng, ZG, et al. Overexpression of phosphodiesterase-4 subtypes involved in surgery-induced neuroinflammation and cognitive dysfunction in mice. Brain Res Bull 2017; 130: 274–82Google Scholar

Wei, P, Zheng, Q, Liu, H, et al. Nicotine-induced neuroprotection against cognitive dysfunction after partial hepatectomy involves activation of BDNF/TrkB signaling pathway and inhibition of NF-kappaB signaling pathway in aged rats. Nicotine Tob Res 2018; 20: 515–22Google Scholar

Wei, C, Luo, T, Zou, S, et al. Differentially expressed lncRNAs and miRNAs with associated ceRNA networks in aged mice with postoperative cognitive dysfunction. Oncotarget 2017; 8: 55901–14Google Scholar

Zhang, C, Zhang, Y, Shen, Y, Zhao, G, Xie, Z, Dong, Y. Anesthesia/surgery induces cognitive impairment in female Alzheimer’s disease transgenic mice. J Alzheimers Dis 2017; 57: 505–18Google Scholar

Zhang, Z, Yuan, H, Zhao, H, Qi, B, Li, F, An, L. PPARgamma activation ameliorates postoperative cognitive decline probably through suppressing hippocampal neuroinflammation in aged mice. Int Immunopharmacol 2017; 43: 53–61Google Scholar

Cao, M, Fang, J, Wang, X, et al. Activation of AMP-activated protein kinase (AMPK) aggravated postoperative cognitive dysfunction and pathogenesis in aged rats. Brain Res 2018; 1684: 21–9Google Scholar

Kong, ZH, Chen, X, Hua, HP, Liang, L, Liu, LJ. The oral pretreatment of glycyrrhizin prevents surgery-induced cognitive impairment in aged mice by reducing neuroinflammation and Alzheimer’s-related pathology via HMGB1 inhibition. J Mol Neurosci 2017; 63: 385–95Google Scholar

Li, W, Chai, Q, Zhang, H, et al. High doses of minocycline may induce delayed activation of microglia in aged rats and thus cannot prevent postoperative cognitive dysfunction. J Int Med Res 2018; 46: 1404–13Google Scholar

Wei, L, Yao, M, Zhao, Z, Jiang, H, Ge, S. High-fat diet aggravates postoperative cognitive dysfunction in aged mice. BMC Anesthesiol 2018; 18: 20Google Scholar

Xiao, JY, Xiong, BR, Zhang, W, et al. PGE2-EP3 signaling exacerbates hippocampus-dependent cognitive impairment after laparotomy by reducing expression levels of hippocampal synaptic plasticity-related proteins in aged mice. CNS Neurosci Ther 2018; doi:10.1111/cns.12832. 24: 917–29Google Scholar

Eckenhoff, R. G., Johansson, J. S., Wei, H., Carnini, A., Kang, B., Wei, W., et al. Inhaled anesthetic enhancement of amyloid-beta oligomerization and cytotoxicity. Anesthesiology 2004; 101: 703–9.Google Scholar

Moller, J. T., Cluitmans, P., Rasmussen, L. S., Houx, P., Rasmussen, H., Canet, J., et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study: ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. The Lancet 1998; 351: 857–61.Google Scholar

Zhang, G., Dong, Y., Zhang, B., Ichinose, F., Wu, X., Culley, D. J., et al. Isoflurane-induced caspase-3 activation is dependent on cytosolic calcium and can be attenuated by memantine. J Neurosci 2008; 28: 4551–60.Google Scholar

Zhang, Y., Xu, Z., Wang, H., Dong, Y., Shi, H. N., Culley, D. J., et al. Anesthetics isoflurane and desflurane differently affect mitochondrial function, learning, and memory. Ann Neurol 2012; 71: 687–98.Google Scholar

Wang, H., Dong, Y., Zhang, J., Xu, Z., Wang, G., Swain, C. A., et al. Isoflurane induces endoplasmic reticulum stress and caspase activation through ryanodine receptors. Br J Anaesth 2014; 113: 695–707.Google Scholar

Ni, C., Li, Z., Qian, M., Zhou, Y., Wang, J., Guo, X.. Isoflurane induced cognitive impairment in aged rats through hippocampal calcineurin/NFAT signaling. Biochem Biophys Res Commun 2015; 460: 889–95.Google Scholar

Stratmann, G., Sall, J. W., Bell, J. S., Alvi, R. S., May, L., Ku, B., et al. Isoflurane does not affect brain cell death, hippocampal neurogenesis, or long-term neurocognitive outcome in aged rats. Anesthesiology 2010; 112: 305–15.Google Scholar

Dong, Y., Zhang, G., Zhang, B., Moir, R. D., Xia, W., Marcantonio, E. R., et al. The common inhalational anesthetic sevoflurane induces apoptosis and increases beta-amyloid protein levels. Arch Neurol 2009; 66: 620–31.Google Scholar

Satomoto, M., Satoh, Y., Terui, K., Miyao, H., Takishima, K., Ito, M., et al. Neonatal exposure to sevoflurane induces abnormal social behaviors and deficits in fear conditioning in mice. Anesthesiology 2009; 110: 628–37.Google Scholar

Shih, J., May, L. D., Gonzalez, H. E., Lee, E. W., Alvi, R. S., Sall, J. W., et al. Delayed environmental enrichment reverses sevoflurane-induced memory impairment in rats. Anesthesiology 2012; 116: 586–602.Google Scholar

Kodama, M., Satoh, Y., Otsubo, Y., Araki, Y., Yonamine, R., Masui, K., et al. Neonatal desflurane exposure induces more robust neuroapoptosis than do isoflurane and sevoflurane and impairs working memory. Anesthesiology 2011; 115: 979–91.Google Scholar

Istaphanous, G. K., Howard, J., Nan, X., Hughes, E. A., McCann, J. C., McAuliffe, J. J., et al. Comparison of the neuroapoptotic properties of equipotent anesthetic concentrations of desflurane, isoflurane, or sevoflurane in neonatal mice. Anesthesiology 2011; 114: 578–87.Google Scholar

Yamakura, T., Harris, R. A.. Effects of gaseous anesthetics nitrous oxide and xenon on ligand-gated ion channels: comparison with isoflurane and ethanol. Anesthesiology 2000; 93: 1095–101.Google Scholar

Deacon, R., Lumb, M., Perry, J., Chanarin, I., Minty, B., Halsey, M. J., et al. Selective inactivation of vitamin B12 in rats by nitrous oxide. The Lancet 1978; 2: 1023–4.Google Scholar

Cohen Aubart, F., Sedel, F., Vicart, S., Lyon-Caen, O., Fontaine, B.. Nitric-oxide triggered neurological disorders in subjects with vitamin B12 deficiency. Rev Neurol (Paris) 2007; 163: 362–4.Google Scholar

Layzer, R. B.. Myeloneuropathy after prolonged exposure to nitrous oxide. The Lancet 1978; 2: 1227–30.Google Scholar

Jevtović-Todorović, V., Beals, J., Benshoff, N., Olney, J. W.. Prolonged exposure to inhalational anesthetic nitrous oxide kills neurons in adult rat brain. Neuroscience 2003; 122: 609–16.Google Scholar

Zhen, Y., Dong, Y., Wu, X., Xu, Z., Lu, Y., Zhang, Y., et al. Nitrous oxide plus isoflurane induces apoptosis and increases beta-amyloid protein levels. Anesthesiology 2009; 111: 741–52.Google Scholar

Young, C., Jevtović-Todorović, V., Qin, Y. Q., Tenkova, T., Wang, H., Labruyere, J., et al. Potential of ketamine and midazolam, individually or in combination, to induce apoptotic neurodegeneration in the infant mouse brain. Br J Pharmacol 2005; 146: 189–97.Google Scholar

Kahraman, S., Zup, S. L., McCarthy, M. M., Fiskum, G.. GABAergic mechanism of propofol toxicity in immature neurons. J Neurosurg Anesthesiol 2008; 20: 233–40.Google Scholar

Pearn, M. L., Hu, Y., Niesman, I. R., Patel, H. H., Drummond, J. C., Roth, D. M., et al. Propofol neurotoxicity is mediated by p75 neurotrophin receptor activation. Anesthesiology 2012; 116: 352–61.Google Scholar

Cattano, D., Young, C., Straiko, M. M., Olney, J. W.. Subanesthetic doses of propofol induce neuroapoptosis in the infant mouse brain. Anesth Analg 2008; 106: 1712–14.Google Scholar

Sun, L. S., Li, G., DiMaggio, C. J., Byrne, M. W., Ing, C., Miller, T. L., et al. Feasibility and pilot study of the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project. J Neurosurg Anesthesiol 2012; 24: 382–8.Google Scholar

Whittington, R. A., Virag, L., Marcouiller, F., Papon, M. A., El Khoury, N. B., Julien, C., et al. Propofol directly increases tau phosphorylation. PLoS One 2011; 6: e16648.Google Scholar

Grundke-Iqbal, I., Iqbal, K., Tung, Y. C., Quinlan, M., Wisniewski, H. M., Binder, L. I.. Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci USA 1986; 83: 4913–17.Google Scholar

Paule, M. G., Li, M., Allen, R. R., Liu, F., Zou, X., Hotchkiss, C., et al. Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys. Neurotoxicol Teratol 2011; 33: 220–30.Google Scholar

Wang, C., Sadovova, N., Fu, X., Schmued, L., Scallet, A., Hanig, J., et al. The role of the N-methyl-D-aspartate receptor in ketamine-induced apoptosis in rat forebrain culture. Neuroscience 2005; 132: 967–77.Google Scholar

Dasgupta, M., Dumbrell, A. C.. Preoperative risk assessment for delirium after noncardiac surgery: a systematic review. J Am Geriatr Soc 2006; 54: 1578–89.Google Scholar

Zhang, B., Tian, M., Zheng, H., Zhen, Y., Yue, Y., Li, T., et al. Effects of anesthetic isoflurane and desflurane on human cerebrospinal fluid Aβ and tau level. Anesthesiology 2013; 119: 52–60.Google Scholar

Xie, Z., McAuliffe, S., Swain, C. A., Ward, S. A., Crosby, C. A., Zheng, H., et al. Cerebrospinal fluid aβ to tau ratio and postoperative cognitive change. Ann Surg 2013; 258: 364–9.Google Scholar

Shaw, L. M., Vanderstichele, H., Knapik-Czajka, M., Clark, C. M., Aisen, P. S., Petersen, R. C., et al. Cerebrospinal fluid biomarker signature in Alzheimer’s disease neuroimaging initiative subjects. Ann Neurol 2009; 65: 403–13.Google Scholar

Zhang, B., Tian, M., Zhen, Y., Yue, Y., Sherman, J., Zheng, H., et al. The effects of isoflurane and desflurane on cognitive function in humans. Anesth Analg 2012; 114: 410–15.Google Scholar

Michenfelder, J. D., Theye, R. A.. Cerebral protection by thiopental during hypoxia. Anesthesiology 1973; 39: 510–17.Google Scholar

Lavine, S. D., Masri, L. S., Levy, M. L., Giannotta, S. L.. Temporary occlusion of the middle cerebral artery in intracranial aneurysm surgery: time limitation and advantage of brain protection. J Neurosurg 1997; 87: 817–24.Google Scholar

Zaidan, J. R., Klochany, A., Martin, W. M., Ziegler, J. S., Harless, D. M., Andrews, R. B.. Effect of thiopental on neurologic outcome following coronary artery bypass grafting. Anesthesiology 1991; 74: 406–11.Google Scholar

Kaisti, K. K., Langsjo, J. W., Aalto, S., Oikonen, V., Sipila, H., Teras, M., et al. Effects of sevoflurane, propofol, and adjunct nitrous oxide on regional cerebral blood flow, oxygen consumption, and blood volume in humans. Anesthesiology 2003; 99: 603–13.Google Scholar

Gelb, A. W., Bayona, N. A., Wilson, J. X., Cechetto, D. F.. Propofol anesthesia compared to awake reduces infarct size in rats. Anesthesiology 2002; 96: 1183–90.Google Scholar

Green, T. R., Bennett, S. R., Nelson, V. M.. Specificity and properties of propofol as an antioxidant free radical scavenger. Toxicol Appl Pharmacol 1994; 129: 163–9.Google Scholar

Adembri, C., Venturi, L., Tani, A., Chiarugi, A., Gramigni, E., Cozzi, A., et al. Neuroprotective effects of propofol in models of cerebral ischemia: inhibition of mitochondrial swelling as a possible mechanism. Anesthesiology 2006; 104: 80–9.Google Scholar

Wei, H., Inan, S.. Dual effects of neuroprotection and neurotoxicity by general anesthetics: role of intracellular calcium homeostasis. Prog Neuropsychopharmacol Biol Psychiatry 2013; 47: 156–61.Google Scholar

Lee, J. J., Li, L., Jung, H. H., Zuo, Z.. Postconditioning with isoflurane reduced ischemia-induced brain injury in rats. Anesthesiology 2008; 108: 1055–62.Google Scholar

Sakai, H., Sheng, H., Yates, R. B., Ishida, K., Pearlstein, R. D., Warner, D. S.. Isoflurane provides long-term protection against focal cerebral ischemia in the rat. Anesthesiology 2007; 106: 92–9; discussion 8–10.Google Scholar

Bilotta, F., Gelb, A. W., Stazi, E., Titi, L., Paoloni, F. P., Rosa, G.. Pharmacological perioperative brain neuroprotection: a qualitative review of randomized clinical trials. Br J Anaesth 2013; 110 Suppl 1: 113–20.Google Scholar

Ishida, K., Berger, M., Nadler, J., Warner, D. S.. Anesthetic neuroprotection: antecedents and an appraisal of preclinical and clinical data quality. Curr Pharm Des 2014; 20: 5751–65.Google Scholar

Xie, Z., Dong, Y., Maeda, U., Alfille, P., Culley, D. J., Crosby, G., et al. The common inhalation anesthetic isoflurane induces apoptosis and increases amyloid beta protein levels. Anesthesiology 2006; 104: 988–94.Google Scholar

Shen, X., Dong, Y., Xu, Z., Wang, H., Miao, C., Soriano, S. G., et al. Selective anesthesia-induced neuroinflammation in developing mouse brain and cognitive impairment. Anesthesiology 2013; 118: 502–15.Google Scholar

Hu, N., Guo, D., Wang, H., Xie, K., Wang, C., Li, Y., et al. Involvement of the blood-brain barrier opening in cognitive decline in aged rats following orthopedic surgery and high concentration of sevoflurane inhalation. Brain Res 2014; 1551: 13–24.Google Scholar

Zhang, B., Dong, Y., Zhang, G., Moir, R. D., Xia, W., Yue, Y., et al. The inhalation anesthetic desflurane induces caspase activation and increases amyloid beta-protein levels under hypoxic conditions. J Biol Chem 2008; 283: 11866–75.Google Scholar

Callaway, J. K., Jones, N. C., Royse, A. G., Royse, C. F.. Memory impairment in rats after desflurane anesthesia is age and dose dependent. J Alzheimers Dis 2015; 44: 995–1005.Google Scholar

Moller, J. T., Cluitmans, P., Rasmussen, L. S., et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. The Lancet. 1998; 351:857–61.Google Scholar

Monk, T. G., Weldon, B. C., Garvan, C. W., et al. Predictors of cognitive dysfunction after major noncardiac surgery. Anesthesiology. 2008; 108:18–30.Google Scholar

Newman, M. F., Kirchner, J. L., Phillips-Bute, B., et al. Longitudinal assessment of neurocognitive function after coronary-artery bypass surgery. N Engl J Med. 2001; 344:395–402.Google Scholar

Steinmetz, J., Christensen, K. B., Lund, T., et al. Long-term consequences of postoperative cognitive dysfunction. Anesthesiology. 2009; 110:548–55.Google Scholar

Riedel, G., Platt, B., Micheau, J.. Glutamate receptor function in learning and memory. Behav Brain Res. 2003; 140:1–47.Google Scholar

Solomonia, R. O., McCabe, B. J.. Molecular mechanisms of memory in imprinting. Neurosci Biobehav Rev. 2015; 50:56–69.Google Scholar

Wevers, A.. Localisation of pre- and postsynaptic cholinergic markers in the human brain. Behav Brain Res. 2011; 221:341–55.Google Scholar

Cheng, Q., Yakel, J. L.. The effect of alpha7 nicotinic receptor activation on glutamatergic transmission in the hippocampus. Biochem Pharmacol. 2015; http://dx.doi.org/10.1016/j.bcp.2015.07.015Google Scholar

Asztely, F., Gustafsson, B.. Ionotropic glutamate receptors: their possible role in the expression of hippocampal synaptic plasticity. Mol Neurobiol. 1996; 12:1–11.Google Scholar

Ulas, J., Brunner, L. C., Geddes, J. W., et al. N-methyl-D-aspartate receptor complex in the hippocampus of elderly, normal individuals and those with Alzheimer’s disease. Neuroscience. 1992; 49:45–61.Google Scholar

Cao, J., Tan, H., Mi, W., et al. Glutamate transporter type 3 regulates mouse hippocampal GluR1 trafficking. Biochim Biophys Acta. 2014; 1840:1640–5.Google Scholar

Sivilotti, L., Nistri, A.. GABA receptor mechanisms in the central nervous system. Prog Neurobiol. 1991; 36:35–92.Google Scholar

Udden, J., Folia, V., Petersson, K. M.. The neuropharmacology of implicit learning. Curr Neuropharmacol. 2010; 8:367–81.Google Scholar

Molas, S., Dierssen, M.. The role of nicotinic receptors in shaping and functioning of the glutamatergic system: a window into cognitive pathology. Neurosci Biobehav Rev. 2014; 46 Pt 2:315–25.Google Scholar

Davies, P., Maloney, A. J.. Selective loss of central cholinergic neurons in Alzheimer’s disease. The Lancet. 1976; 2:1403.Google Scholar

Miyazawa, A., Fujiyoshi, Y., Unwin, N.. Structure and gating mechanism of the acetylcholine receptor pore. Nature. 2003; 423:949–55.Google Scholar

Deiana, S., Platt, B., Riedel, G.. The cholinergic system and spatial learning. Behav Brain Res. 2011; 221:389–411.Google Scholar

Zhang, X., Xin, X., Dong, Y., et al. Surgical incision-induced nociception causes cognitive impairment and reduction in synaptic NMDA receptor 2B in mice. J Neurosci. 2013; 33:17737–48.Google Scholar

Chi, H., Kawano, T., Tamura, T., et al. Postoperative pain impairs subsequent performance on a spatial memory task via effects on N-methyl-D-aspartate receptor in aged rats. Life Sci. 2013; 93:986–93.Google Scholar

Zuo, Z.. Are volatile anesthetics neuroprotective or neurotoxic? Med Gas Res. 2012; 2:10.Google Scholar

Rammes, G., Starker, L. K., Haseneder, R., et al. Isoflurane anaesthesia reversibly improves cognitive function and long-term potentiation (LTP) via an up-regulation in NMDA receptor 2B subunit expression. Neuropharmacology. 2009; 56:626–36.Google Scholar

Hu, N., Wang, M., Xie, K., et al. Internalization of GluA2 and the underlying mechanisms of cognitive decline in aged rats following surgery and prolonged exposure to sevoflurane. Neurotoxicology. 2015; 49:94–103.Google Scholar

Liu, J., Wang, P., Zhang, X., et al. Effects of different concentration and duration time of isoflurane on acute and long-term neurocognitive function of young adult C57BL/6 mouse. Int J Clin Exp Pathol. 2014; 7:5828–36.Google Scholar

Mawhinney, L. J., de Rivero Vaccari, J. P., Alonso, O. F., et al. Isoflurane/nitrous oxide anesthesia induces increases in NMDA receptor subunit NR2B protein expression in the aged rat brain. Brain Res. 2012; 1431:23–34.Google Scholar

Lin, D., Zuo, Z.. Isoflurane induces hippocampal cell injury and cognitive impairments in adult rats. Neuropharmacology. 2011; 61:1354–9.Google Scholar

Cao, L., Li, L., Lin, D., et al. Isoflurane induces learning impairment that is mediated by interleukin 1β in rodents. PLoS One. 2012; 7:e51431.Google Scholar

Zhang, J., Tan, H., Jiang, W., et al. Amantadine alleviates postoperative cognitive dysfunction possibly by increasing glial cell line-derived neurotrophic factor in rats. Anesthesiology. 2014; 121:773–85.Google Scholar

Zhang, J., Jiang, W., Zuo, Z.. Pyrrolidine dithiocarbamate attenuates surgery-induced neuroinflammation and cognitive dysfunction possibly via inhibition of nuclear factor kappaB. Neuroscience. 2014; 261:1–10.Google Scholar

Terrando, N., Eriksson, L. I., Ryu, J. K., et al. Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol. 2011; 70:986–95.Google Scholar

Xie, W., Yang, Y., Gu, X., et al. Senegenin attenuates hepatic ischemia-reperfusion induced cognitive dysfunction by increasing hippocampal NR2B expression in rats. PLoS One. 2012; 7:e45575.Google Scholar

Tan, H., Cao, J., Zhang, J., et al. Critical role of inflammatory cytokines in impairing biochemical processes for learning and memory after surgery in rats. J Neuroinflammation. 2014; 11:93.Google Scholar

Rossi, A., Burkhart, C., Dell-Kuster, S., et al. Serum anticholinergic activity and postoperative cognitive dysfunction in elderly patients. Anesth Analg. 2014; 119:947–55.Google Scholar

Plaschke, K., Hauth, S., Jansen, C., et al. The influence of preoperative serum anticholinergic activity and other risk factors for the development of postoperative cognitive dysfunction after cardiac surgery. J Thorac Cardiovasc Surg. 2013; 145:805–11.Google Scholar

Xiong, J., Xue, F. S., Liu, J. H., et al. Transcutaneous vagus nerve stimulation may attenuate postoperative cognitive dysfunction in elderly patients. Med Hypotheses. 2009; 73:938–41.Google Scholar

Wang, H., Xu, Z. P., Feng, C. S., et al. Correlation of hippocampal acetylcholine and learning and study capability after anesthesia in senescent rats. Zhonghua Yi Xue Za Zhi. 2009; 89:2309–14.Google Scholar

Kalb, A., von Haefen, C., Sifringer, M., et al. Acetylcholinesterase inhibitors reduce neuroinflammation and -degeneration in the cortex and hippocampus of a surgery stress rat model. PLoS One. 2013; 8:e62679.Google Scholar

Terrando, N., Yang, T., Ryu, J. K., et al. Stimulation of the alpha7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice. Mol Med. 2014; 20:667–75.Google Scholar

Li, Z., Cao, Y., Li, L., et al. Prophylactic angiotensin type 1 receptor antagonism confers neuroprotection in an aged rat model of postoperative cognitive dysfunction. Biochem Biophys Res Commun. 2014; 449:74–80.Google Scholar

Saavedra, J. M.. Angiotensin II AT(1) receptor blockers as treatments for inflammatory brain disorders. Clin Sci (Lond). 2012; 123:567–90.Google Scholar

Takeda, S., Sato, N., Takeuchi, D., et al. Angiotensin receptor blocker prevented beta-amyloid-induced cognitive impairment associated with recovery of neurovascular coupling. Hypertension. 2009; 54:1345–52.Google Scholar

Saab, B. J., Maclean, A. J., Kanisek, M., et al. Short-term memory impairment after isoflurane in mice is prevented by the alpha5 gamma-aminobutyric acid type A receptor inverse agonist L-655,708. Anesthesiology. 2010; 113:1061–71.Google Scholar

Zurek, A., Yu, J., Wang, D. S., et al. Sustained increase in alpha5GABAA receptor function impairs memory after anesthesia. J Clin Invest. 2014; 124:5437–41.Google Scholar

Wang, D. S., Zurek, A. A., Lecker, I., et al. Memory deficits induced by inflammation are regulated by alpha5-subunit-containing GABAA receptors. Cell Rep. 2012; 2:488–96.Google Scholar

Health and Social Care Information Centre. National Statistics hospital episode statistics, admitted patient care, England – 2013–14. 2015.Google Scholar

Alam, A, Hana, Z, Zhaosheng, JK, Suen, KC, Ma D. Surgery, neuroinflammation and cognitive impairment. EBioMedicine 2018; S2352-3964(18):30432–30438.Google Scholar

Bone, RC, Grodzin, CJ, Balk, RA. Sepsis: a new hypothesis for pathogenesis of the disease process. Chest 1997;112(1):235–243.Google Scholar

Bone, RC, Balk, RA, Cerra, FB, Dellinger, RP, Fein, AM, Knaus, WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest 1992; 101(6):1644–1655.Google Scholar

Ologunde, R, Zhao, H, Lu, K, Ma, D. Organ cross talk and remote organ damage following acute kidney injury. Int Urol Nephrol 2014;46(12):2337–2345.Google Scholar

Mann, DL. Mechanisms and models in heart failure: a combinatorial approach. Circulation 1999;100(9):999–1008.Google Scholar

Lyman, M, Ma, D. Surgery, neuroinflammation and long-term outcome. J Anesth Perioper Med 2014 2014;1(2):122.Google Scholar

Zakharova, M, Ziegler, HK. Paradoxical anti-inflammatory actions of TNF-alpha: inhibition of IL-12 and IL-23 via TNF receptor 1 in macrophages and dendritic cells. J Immunol 2005;175(8):5024–5033.Google Scholar

Beggs, S, Liu, XJ, Kwan, C, Salter, MW. Peripheral nerve injury and TRPV1-expressing primary afferent C-fibers cause opening of the blood-brain barrier. Mol Pain 2010;6:74.Google Scholar

Lyman, M, Lloyd, DG, Ji, X, Vizcaychipi, MP, Ma, D. Neuroinflammation: the role and consequences. Neurosci Res 2014;79:1–12.Google Scholar

Kuhn, HG, Dickinson-Anson, H, Gage, FH. Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci 1996;16(6):2027–2033.Google Scholar

Ekdahl, CT, Claasen, JH, Bonde, S, Kokaia, Z, Lindvall, O. Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci USA 2003;100(23):13632–13637.Google Scholar

Terrando, N, Eriksson, LI, Ryu, JK, Yang, T, Monaco, C, Feldmann, M, et al. Resolving postoperative neuroinflammation and cognitive decline. Ann Neurol 2011;70(6):986–995.Google Scholar

Moller, JT, Cluitmans, P, Rasmussen, LS, Houx, P, Rasmussen, H, Canet, J, et al. Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. The Lancet 1998;351(9106):857–861.Google Scholar

Hebert, LE, Bienias, JL, Aggarwal, NT, Wilson, RS, Bennett, DA, Shah, RC, et al. Change in risk of Alzheimer disease over time. Neurology 2010;75(9):786–791.Google Scholar

Vanderweyde, T, Bednar, MM, Forman, SA, Wolozin, B. Iatrogenic risk factors for Alzheimer’s disease: surgery and anesthesia. J Alzheimers Dis 2010;22 Suppl 3:91–104.Google Scholar

Kapila, AK, Watts, HR, Wang, T, Ma, D. The impact of surgery and anesthesia on post-operative cognitive decline and Alzheimer’s disease development: biomarkers and preventive strategies. J Alzheimers Dis 2014;41(1):1–13.Google Scholar

Vizcaychipi, MP, Watts, HR, O’Dea, KP, Lloyd, DG, Penn, JW, Wan, Y, et al. The therapeutic potential of atorvastatin in a mouse model of postoperative cognitive decline. Ann Surg 2014;259(6):1235–1244.Google Scholar

Pac-Soo, C, Lloyd, DG, Vizcaychipi, MP, Ma, D. Statins: the role in the treatment and prevention of Alzheimer’s neurodegeneration. J Alzheimers Dis 2011;27(1):1–10.Google Scholar

Vizcaychipi, MP, Lloyd, DG, Wan, Y, Palazzo, MG, Maze, M, Ma, D. Xenon pretreatment may prevent early memory decline after isoflurane anesthesia and surgery in mice. PLoS One 2011;6(11):e26394.Google Scholar

Saravanan, P, Exley, AR, Valchanov, K, Casey, ND, Falter, F. Impact of xenon anaesthesia in isolated cardiopulmonary bypass on very early leucocyte and platelet activation and clearance: a randomized, controlled study. Br J Anaesth 2009;103(6):805–810.Google Scholar

Terrando, N, Yang, T, Ryu, JK, Newton, PT, Monaco, C, Feldmann, M, et al. Stimulation of the alpha7 nicotinic acetylcholine receptor protects against neuroinflammation after tibia fracture and endotoxemia in mice. Mol Med 2015;20:667–675.Google Scholar

Ancelin, ML, et al. (2001) Exposure to anaesthetic agents, cognitive functioning and depressive symptomatology in the elderly. British Journal of Psychiatry 178:360–366.Google Scholar

Hudetz, JA, Patterson, KM, Amole, O, Riley, AV, & Pagel, PS (2011) Postoperative cognitive dysfunction after noncardiac surgery: effects of metabolic syndrome. Journal of Anesthesia 25(3):337–344.Google Scholar

Hudetz, JA, Patterson, KM, Iqbal, Z, Gandhi, SD, & Pagel, PS (2011) Metabolic syndrome exacerbates short-term postoperative cognitive dysfunction in patients undergoing cardiac surgery: results of a pilot study. Journal of Cardiothoracic and Vascular Anesthesia 25(2):282–287.Google Scholar

Moller, JT, et al. (1998) Long-term postoperative cognitive dysfunction in the elderly ISPOCD1 study. ISPOCD investigators. International Study of Post-Operative Cognitive Dysfunction. The Lancet 351(9106):857–861.Google Scholar

Weiser, TG, et al. (2008) An estimation of the global volume of surgery: a modelling strategy based on available data. The Lancet 372(9633):139–144.Google Scholar

Krenk, L, Rasmussen, LS, & Kehlet, H (2010) New insights into the pathophysiology of postoperative cognitive dysfunction. Acta Anaesthesiologica Scandinavica 54(8):951–956.Google Scholar

Ansaloni, L, et al. (2010) Risk factors and incidence of postoperative delirium in elderly patients after elective and emergency surgery. British Journal of Surgery 97(2):273–280.Google Scholar

Abildstrom, H, et al. (2000) Cognitive dysfunction 1–2 years after non-cardiac surgery in the elderly. ISPOCD group. International Study of Post-Operative Cognitive Dysfunction. Acta Anaesthesiologica Scandinavica 44(10):1246–1251.Google Scholar

Roach, GW, et al. (1996) Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. New England Journal of Medicine 335(25):1857–1863.Google Scholar

Stockton, P, Cohen-Mansfield, J, & Billig, N (2000) Mental status change in older surgical patients: cognition, depression, and other comorbidity. American Journal of Geriatric Psychiatry 8(1):40–46.Google Scholar

Rasmussen, LS (2006) Postoperative cognitive dysfunction: incidence and prevention: best practice and research. Clinical Anaesthesiology 20(2):315–330.Google Scholar

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. Journal of Neuroscience 32(42):14641–14648.Google Scholar

Cibelli, M, et al. (2010) Role of interleukin-1beta in postoperative cognitive dysfunction. Annals of Neurology 68(3):360–368.Google Scholar

Tang, JX, et al. (2011) Human Alzheimer and inflammation biomarkers after anesthesia and surgery. Anesthesiology 115(4):727–732.Google Scholar

Wan, Y, et al. (2007) Postoperative impairment of cognitive function in rats: a possible role for cytokine-mediated inflammation in the hippocampus. Anesthesiology 106(3):436–443.Google Scholar

Yirmiya, R & Goshen, I (2011) Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain, Behavior, and Immunity 25(2):181–213.Google Scholar

Fidalgo, AR, et al. (2011) Peripheral orthopaedic surgery down-regulates hippocampal brain-derived neurotrophic factor and impairs remote memory in mouse. Neuroscience 190:194–199.Google Scholar

Hovens, IB, et al. (2014) Postoperative cognitive dysfunction: involvement of neuroinflammation and neuronal functioning. Brain, Behavior, and Immunity 38:202–210.Google Scholar

Peng, L, Xu, L, & Ouyang, W (2013) Role of peripheral inflammatory markers in postoperative cognitive dysfunction (POCD): a meta-analysis. PLoS One 8(11):e79624.Google Scholar

Ramlawi, B, et al. (2006) C-Reactive protein and inflammatory response associated to neurocognitive decline following cardiac surgery. Surgery 140(2):221–226.Google Scholar

Terrando, N, et al. (2010) Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proceedings of the National Academy of Sciences of the United States of America 107(47):20518–20522.Google Scholar

Dilger, RN & Johnson, RW (2008) Aging, microglial cell priming, and the discordant central inflammatory response to signals from the peripheral immune system. Journal of Leukocyte Biology 84(4):932–939.Google Scholar

Luz Correa, B, et al. (2014) The inverted CD4:CD8 ratio is associated with cytomegalovirus, poor cognitive and functional states in older adults. Neuroimmunomodulation 21(4):206–212.Google Scholar

Martorana, A, et al. (2012) Immunosenescence, inflammation and Alzheimer’s disease. Longevity and Healthspan 1:8.Google Scholar

Shaw, AC, Joshi, S, Greenwood, H, Panda, A, & Lord, JM (2010) Aging of the innate immune system. Current Opinion in Immunology 22(4):507–513.Google Scholar

Lucin, KM & Wyss-Coray, T (2009) Immune activation in brain aging and neurodegeneration: too much or too little? Neuron 64(1):110–122.Google Scholar

Tracey, KJ (2009) Reflex control of immunity. Nature Reviews Immunology 9(6):418–428.Google Scholar

Serhan, CN (2011) The resolution of inflammation: the devil in the flask and in the details. FASEB Journal 25(5):1441–1448.Google Scholar

Serhan, CN, Chiang, N, & Van Dyke, TE (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nature Reviews Immunology 8(5):349–361.Google Scholar

Spite, M & Serhan, CN (2010) Novel lipid mediators promote resolution of acute inflammation: impact of aspirin and statins. Circulation Research 107(10):1170–1184.Google Scholar

Chawla, A, Nguyen, KD, & Goh, YP (2011) Macrophage-mediated inflammation in metabolic disease. Nature Reviews Immunology 11(11):738–749.Google Scholar

Odegaard, JI, et al. (2008) Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. Cell Metabolism 7(6):496–507.Google Scholar

Abeywardena, MY & Patten, GS (2011) Role of omega3 long-chain polyunsaturated fatty acids in reducing cardio-metabolic risk factors. Endocrine, Metabolic and Immune Disorders Drug Targets 11(3):232–246.Google Scholar

Masson, CJ & Mensink, RP (2011) Exchanging saturated fatty acids for (n-6) polyunsaturated fatty acids in a mixed meal may decrease postprandial lipemia and markers of inflammation and endothelial activity in overweight men. Journal of Nutrition 141(5):816–821.Google Scholar

Bernik, TR, et al. (2002) Pharmacological stimulation of the cholinergic antiinflammatory pathway. Journal of Experimental Medicine 195(6):781–788.Google Scholar

Wang, H, et al. (2003) Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 421(6921):384–388.Google Scholar

Borovikova, LV, et al. (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405(6785):458–462.Google Scholar

van Maanen, MA, Stoof, SP, Larosa, GJ, Vervoordeldonk, MJ, & Tak, PP (2010) Role of the cholinergic nervous system in rheumatoid arthritis: aggravation of arthritis in nicotinic acetylcholine receptor alpha7 subunit gene knockout mice. Annals of the Rheumatic Diseases 69(9):1717–1723.Google Scholar

Ghia, JE, Blennerhassett, P, El-Sharkawy, RT, & Collins, SM (2007) The protective effect of the vagus nerve in a murine model of chronic relapsing colitis. Gastrointestinal and Liver Physiology 293(4):711–718.Google Scholar

O’Mahony, C, van der Kleij, H, Bienenstock, J, Shanahan, F, & O’Mahony, L (2009) Loss of vagal anti-inflammatory effect: in vivo visualization and adoptive transfer. American Journal of Physiology 297(4):1118–1126.Google Scholar

Rosas-Ballina, M, et al. (2011) Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science 334(6052):98–101.Google Scholar

de Jonge, WJ, et al. (2005) Stimulation of the vagus nerve attenuates macrophage activation by activating the Jak2-STAT3 signaling pathway. Nature Immunology 6(8):844–851.Google Scholar

Fujisaka, S, et al. (2009) Regulatory mechanisms for adipose tissue M1 and M2 macrophages in diet-induced obese mice. Diabetes 58(11):2574–2582.Google Scholar

Godbout, JP & Johnson, RW (2009) Age and neuroinflammation: a lifetime of psychoneuroimmune consequences. Immunology and Allergy Clinics of North America 29(2):321–337.Google Scholar

Hovens, IB, et al. (2015) Prior infection exacerbates postoperative cognitive dysfunction in aged rats. American Journal of Physiology 309(2):148–159.Google Scholar

Hudetz, JA, et al. (2011) Postoperative delirium and short-term cognitive dysfunction occur more frequently in patients undergoing valve surgery with or without coronary artery bypass graft surgery compared with coronary artery bypass graft surgery alone: results of a pilot study. Journal of Cardiothoracic and Vascular Anesthesia 25(5):811–816.Google Scholar

Eckel, RH, Alberti, KG, Grundy, SM, & Zimmet, PZ (2010) The metabolic syndrome. The Lancet 375(9710):181–183.Google Scholar

Kajimoto, K, et al. (2009) Metabolic syndrome is an independent risk factor for stroke and acute renal failure after coronary artery bypass grafting. Journal of Thoracic and Cardiovascular Surgery 137(3):658–663.Google Scholar

Feng, X, et al. (2013) Surgery results in exaggerated and persistent cognitive decline in a rat model of the metabolic syndrome. Anesthesiology 118(5):1098–1105.Google Scholar

Su, X, et al. (2012) Dysfunction of inflammation-resolving pathways is associated with exaggerated postoperative cognitive decline in a rat model of the metabolic syndrome. Molecular Medicine 18:1481–1490.Google Scholar

Terrando, N, et al. (2011) Resolving postoperative neuroinflammation and cognitive decline. Annals of Neurology 70(6):986–995.Google Scholar

Buechler, C, Wanninger, J, & Neumeier, M (2010) Adiponectin receptor binding proteins – recent advances in elucidating adiponectin signalling pathways. FEBS Letters 584(20):4280–4286.Google Scholar

Choudhary, S, et al. (2011) NF-kappaB-inducing kinase (NIK) mediates skeletal muscle insulin resistance: blockade by adiponectin. Endocrinology 152(10):3622–3627.Google Scholar

Puntener, U, Booth, SG, Perry, VH, & Teeling, JL (2012) Long-term impact of systemic bacterial infection on the cerebral vasculature and microglia. Journal of Neuroinflammation 9:146.Google Scholar

Bilbo, SD (2010) Early-life infection is a vulnerability factor for aging-related glial alterations and cognitive decline. Neurobiology of Learning and Memory 94(1):57–64.Google Scholar

Cortese, GP, Barrientos, RM, Maier, SF, & Patterson, SL (2011) Aging and a peripheral immune challenge interact to reduce mature brain-derived neurotrophic factor and activation of TrkB, PLCgamma1, and ERK in hippocampal synaptoneurosomes. Journal of Neuroscience 31(11):4274–4279.Google Scholar

Barrientos, RM, et al. (2006) Peripheral infection and aging interact to impair hippocampal memory consolidation. Neurobiology of Aging 27(5):723–732.Google Scholar

O’Connor, JC, et al. (2009) Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin. Journal of Neuroscience 29(13):4200–4209.Google Scholar

Rector, JL, et al. (2014) Consistent associations between measures of psychological stress and CMV antibody levels in a large occupational sample. Brain, Behavior, and Immunity 38:133–141.Google Scholar

Strandberg, TE, Pitkala, KH, Linnavuori, KH, & Tilvis, RS (2003) Impact of viral and bacterial burden on cognitive impairment in elderly persons with cardiovascular diseases. Stroke 34(9):2126–2131.Google Scholar

Wichmann, MA, et al. (2014) Long-term systemic inflammation and cognitive impairment in a population-based cohort. Journal of the American Geriatrics Society 62(9):1683–1691.Google Scholar

Hovens, IB, et al. (2015) Postoperative cognitive dysfunction and microglial activation in associated brain regions in old rats. Neurobiology of Learning and Memory 118:74–79.Google Scholar

Fidalgo, AR, et al. (2011) Systemic inflammation enhances surgery-induced cognitive dysfunction in mice. Neuroscience Letters 498(1):63–66.Google Scholar