{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T14:41:27Z","timestamp":1783348887685,"version":"3.54.6"},"reference-count":39,"publisher":"SAGE Publications","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2021,6,15]]},"abstract":"<jats:p>Background: Accumulating evidence has demonstrated that aging is associated with an exaggerated response to surgical trauma together with cognitive impairments. This has significant implications for the development of clinical phenotype such as perioperative neurocognitive disorders (PND), which is a common complication following surgery, especially for the elderly. However, the mechanism by which aging brain is vulnerable to surgical trauma remains to be elucidated. Objective: To test whether age-related alterations in hippocampal network activities contribute to increased risk of PND following surgery. Methods: Thirty-two adult and seventy-two aged male C57BL\/6 mice undergone sevoflurane anesthesia and exploratory laparotomy were used to mimic human abdominal surgery. For the interventional study, mice were treated with minocycline. Behavioral tests were performed post-surgery with open field, novel object recognition and fear conditioning tests, respectively. The brain tissues were then harvested and subjected to biochemistry studies. Local field potential (LFP) recording was performed in another separate experiment. Results: Aged mice displayed signs of neuroinflammation, as reflected by significantly increased proinflammatory mediators in the hippocampus. Also, aged mice displayed persistently decreased oscillation activities under different conditions, both before and after surgery. Further correlation analysis suggested that theta power was positively associated with time with novel object, while \u03b3 oscillation activity was positively associated with freezing time to context. Of note, downregulation of neuroinflammation by microglia inhibitor minocycline reversed some of these abnormities. Conclusion: Our study highlights that age-related hippocampal oscillation dysregulation increases the risk of PND incidence, which might provide diagnostic\/prognostic biomarkers for PND and possible other neurodegenerative diseases.<\/jats:p>","DOI":"10.3233\/jad-201590","type":"journal-article","created":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T05:23:47Z","timestamp":1620192227000},"page":"1685-1699","source":"Crossref","is-referenced-by-count":14,"title":["Aging-Related Neural Disruption Might Predispose to Postoperative Cognitive Impairment Following Surgical Trauma"],"prefix":"10.1177","volume":"81","author":[{"given":"Mu-huo","family":"Ji","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, the Second Affiliated Hospital of Nanjing Medical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"He","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-chun","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-jun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-201590_ref1","doi-asserted-by":"crossref","first-page":"112501","DOI":"10.1016\/j.bbr.2020.112501","article-title":"Effects of aging on the motor, cognitive and affective behaviors, neuroimmune responses and hippocampal gene expression","volume":"383","author":"Singhal","year":"2020","journal-title":"Behav Brain Res"},{"key":"10.3233\/JAD-201590_ref2","doi-asserted-by":"crossref","first-page":"e13057","DOI":"10.1111\/acel.13057","article-title":"mTOR drives cerebrovascular, synaptic, and cognitive dysfunction in normative aging","volume":"19","author":"Van Skike","year":"2020","journal-title":"Aging Cell"},{"key":"10.3233\/JAD-201590_ref3","doi-asserted-by":"crossref","first-page":"4900","DOI":"10.1038\/s41467-019-12921-z","article-title":"Tau deposition is associated with functional isolation of the hippocampus in aging","volume":"10","author":"Harrison","year":"2019","journal-title":"Nat Commun"},{"key":"10.3233\/JAD-201590_ref4","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.bbi.2017.01.010","article-title":"Pathophysiological and behavioral effects of systemic inflammation in aged and diseased rodents with relevance to delirium: A systematic review","volume":"62","author":"Schreuder","year":"2017","journal-title":"Brain Behav Immun"},{"key":"10.3233\/JAD-201590_ref5","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1186\/s12974-019-1582-5","article-title":"The broad spectrum mixed-lineage kinase 3 inhibitor URMC-099 prevents acute microgliosis and cognitive decline in a mouse model of perioperative neurocognitive disorders","volume":"16","author":"Miller-Rhodes","year":"2019","journal-title":"J Neuroinflammation"},{"key":"10.3233\/JAD-201590_ref6","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.3233\/JAD-201544","article-title":"Cerebrospinal fluid proteome changes in older non-cardiac surgical patients with postoperative cognitive dysfunction","volume":"80","author":"VanDusen","year":"2021","journal-title":"J Alzheimers Dis"},{"key":"10.3233\/JAD-201590_ref7","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12974-019-1695-x","article-title":"Dysregulation of BDNF\/TrkB signaling mediated by NMDAR\/Ca2+\/calpain might contribute to postoperative cognitive dysfunction in aging mice","volume":"17","author":"Qiu","year":"2020","journal-title":"J Neuroinflammation"},{"key":"10.3233\/JAD-201590_ref8","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1097\/ALN.0000000000002334","article-title":"Recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery-2018","volume":"129","author":"Evered","year":"2018","journal-title":"Anesthesiology"},{"key":"10.3233\/JAD-201590_ref9","doi-asserted-by":"crossref","first-page":"e86258","DOI":"10.1371\/journal.pone.0086258","article-title":"Association of structural global brain network properties with intelligence in normal aging","volume":"9","author":"Fischer","year":"2014","journal-title":"PLoS One"},{"key":"10.3233\/JAD-201590_ref10","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1097\/ALN.0000000000003181","article-title":"Preoperative cognitive abnormality, intraoperative electroencephalogram suppression, and postoperative delirium: A mediation analysis","volume":"132","author":"Fritz","year":"2020","journal-title":"Anesthesiology"},{"key":"10.3233\/JAD-201590_ref11","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1097\/ALN.0000000000000671","article-title":"Preexisting cognitive impairment is associated with postoperative cognitive dysfunction after hip joint replacement surgery","volume":"122","author":"Silbert","year":"2015","journal-title":"Anesthesiology"},{"key":"10.3233\/JAD-201590_ref12","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/s41583-018-0094-0","article-title":"Portraits of communication in neuronal networks","volume":"20","author":"Hahn","year":"2019","journal-title":"Nat Rev Neurosci"},{"key":"10.3233\/JAD-201590_ref13","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.biopsych.2015.04.016","article-title":"Dynamic network communication as a unifying neural basis for cognition, development, aging, and disease","volume":"77","author":"Voytek","year":"2015","journal-title":"Biol Psychiatry"},{"key":"10.3233\/JAD-201590_ref14","doi-asserted-by":"crossref","unstructured":"Law CSH , Leung LS (2018) Long-term potentiation and excitability in the hippocampus are modulated differently by \u03b8 rhythm. eNeuro 5, ENEURO.0236-182018.","DOI":"10.1523\/ENEURO.0236-18.2018"},{"key":"10.3233\/JAD-201590_ref15","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.neuron.2018.09.019","article-title":"Gamma synchronization between v1 and v4 improves behavioral performance","volume":"100","author":"Rohenkohl","year":"2018","journal-title":"Neuron"},{"key":"10.3233\/JAD-201590_ref16","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.neuron.2019.09.039","article-title":"A distinct class of bursting neurons with strong gamma synchronization and stimulus selectivity in monkey V1","volume":"105","author":"Onorato","year":"2020","journal-title":"Neuron"},{"key":"10.3233\/JAD-201590_ref17","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1016\/j.celrep.2019.11.075","article-title":"Physiological signature of memory age in the prefrontal-hippocampal circuit","volume":"29","author":"Makino","year":"2019","journal-title":"Cell Rep"},{"key":"10.3233\/JAD-201590_ref18","doi-asserted-by":"crossref","first-page":"1255263","DOI":"10.1126\/science.1255263","article-title":"Interneurons. fast-spiking, parvalbumin GABAergic interneurons: From cellular design to microcircuit function","volume":"345","author":"Hu","year":"2014","journal-title":"Science"},{"key":"10.3233\/JAD-201590_ref19","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1016\/j.neuron.2016.04.009","article-title":"Apolipoprotein E4 causes age-dependent disruption of slow gamma oscillations during hippocampal sharp-wave ripples","volume":"90","author":"Gillespie","year":"2016","journal-title":"Neuron"},{"key":"10.3233\/JAD-201590_ref20","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.celrep.2019.08.103","article-title":"The amyloid precursor protein C-terminal domain alters ca1 neuron firing, modifying hippocampus oscillations and impairing spatial memory encoding","volume":"29","author":"Fernandez","year":"2019","journal-title":"Cell Rep"},{"key":"10.3233\/JAD-201590_ref21","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.brainres.2014.05.043","article-title":"Age-related differences in working memory evoked gamma oscillations","volume":"1576","author":"Barr","year":"2014","journal-title":"Brain Res"},{"key":"10.3233\/JAD-201590_ref22","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1002\/ana.22082","article-title":"Role of interleukin-1beta in postoperative cognitive dysfunction","volume":"68","author":"Cibelli","year":"2010","journal-title":"Ann Neurol"},{"key":"10.3233\/JAD-201590_ref23","doi-asserted-by":"crossref","first-page":"2471","DOI":"10.18632\/aging.102755","article-title":"Sepsis induced cognitive impairments by disrupting hippocampal parvalbumin interneuron-mediated inhibitory network via a D4-receptor mechanism","volume":"12","author":"Ji","year":"2020","journal-title":"Aging (Albany NY)"},{"key":"10.3233\/JAD-201590_ref24","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/nature10357","article-title":"The ageing systemic milieu negatively regulates neurogenesis and cognitive function","volume":"477","author":"Villeda","year":"2011","journal-title":"Nature"},{"key":"10.3233\/JAD-201590_ref25","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1007\/s11357-011-9301-x","article-title":"The association between systemic inflammation and cognitive performance in the elderly: The Sydney Memory and Ageing Study","volume":"34","author":"Trollor","year":"2012","journal-title":"Age (Dordr)"},{"key":"10.3233\/JAD-201590_ref26","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1136\/bmj.327.7407.128","article-title":"Effect of non-steroidal anti-inflammatory drugs on risk of Alzheimer\u2019s disease: Systematic review and meta-analysis of observational studies","volume":"327","author":"Etminan","year":"2003","journal-title":"BMJ"},{"key":"10.3233\/JAD-201590_ref27","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1002\/glia.23563","article-title":"TREM2 triggers microglial density and age-related neuronal loss","volume":"67","author":"Linnartz-Gerlach","year":"2019","journal-title":"Glia"},{"key":"10.3233\/JAD-201590_ref28","doi-asserted-by":"crossref","unstructured":"Tanaka N , Cortese GP , Barrientos RM , Maier SF , Patterson SL (2018) Aging and an immune challenge interact to produce prolonged, but not permanent, reductions in hippocampal L-LTP and mBDNF in a rodent model with features of delirium. eNeuro 5, ENEURO.0009-18.2018.","DOI":"10.1523\/ENEURO.0009-18.2018"},{"key":"10.3233\/JAD-201590_ref29","doi-asserted-by":"crossref","first-page":"14641","DOI":"10.1523\/JNEUROSCI.2173-12.2012","article-title":"Intracisternal interleukin-1 receptor antagonist prevents postoperative cognitive decline and neuroinflammatory response in aged rats","volume":"32","author":"Barrientos","year":"2012","journal-title":"J Neurosci"},{"key":"10.3233\/JAD-201590_ref30","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.biopsych.2015.03.010","article-title":"Alterations in cortical network oscillations and parvalbumin neurons in schizophrenia","volume":"77","author":"Gonzalez-Burgos","year":"2015","journal-title":"Biol Psychiatry"},{"key":"10.3233\/JAD-201590_ref31","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.ymthe.2016.10.010","article-title":"Correcting miR92a-vGAT-mediated GABAergic dysfunctions rescues human Tau-induced anxiety in mice","volume":"25","author":"Li","year":"2017","journal-title":"Mol Ther"},{"key":"10.3233\/JAD-201590_ref32","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1038\/jcbfm.2014.104","article-title":"Highly energized inhibitory interneurons are a central element for information processing in cortical networks","volume":"34","author":"Kann","year":"2014","journal-title":"J Cereb Blood Flow Metab"},{"key":"10.3233\/JAD-201590_ref33","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.neurobiolaging.2018.08.024","article-title":"Early disruption of parvalbumin expression and perineuronal nets in the hippocampus of the Tg2576 mouse model of Alzheimer\u2019s disease can be rescued by enriched environment","volume":"72","author":"Cattaud","year":"2018","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-201590_ref34","doi-asserted-by":"crossref","first-page":"234","DOI":"10.3389\/fnagi.2016.00234","article-title":"Nox-2-mediated phenotype loss of hippocampal parvalbumin interneurons might contribute to postoperative cognitive decline in aging mice","volume":"8","author":"Qiu","year":"2016","journal-title":"Front Aging Neurosci"},{"key":"10.3233\/JAD-201590_ref35","doi-asserted-by":"crossref","first-page":"431.e1","DOI":"10.1016\/j.neurobiolaging.2010.12.014","article-title":"Interneuron loss reduces dendritic inhibition and GABA release in hippocampus of aged rats","volume":"33","author":"Stanley","year":"2012","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-201590_ref36","doi-asserted-by":"crossref","first-page":"e5518","DOI":"10.1371\/journal.pone.0005518","article-title":"IL-6 mediated degeneration of forebrain GABAergic interneurons and cognitive impairment in aged mice through activation of neuronal NADPH oxidase","volume":"4","author":"Dugan","year":"2009","journal-title":"PLoS One"},{"key":"10.3233\/JAD-201590_ref37","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1007\/s11064-008-9699-4","article-title":"Parvalbumin immunoreactivity and protein level are altered in the gerbil hippocampus during normal aging","volume":"33","author":"Lee","year":"2008","journal-title":"Neurochem Res"},{"key":"10.3233\/JAD-201590_ref38","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/j.neurobiolaging.2011.12.010","article-title":"Age-dependent disruption in hippocampal \u03b8 oscillation in amyloid-\u03b2 overproducing transgenic mice","volume":"33","author":"Scott","year":"2012","journal-title":"Neurobiol Aging"},{"key":"10.3233\/JAD-201590_ref39","doi-asserted-by":"crossref","first-page":"16331","DOI":"10.1523\/JNEUROSCI.1577-12.2012","article-title":"Reduced gamma frequency in the medial frontal cortex of aged rats during behavior and rest: Implications for age-related behavioral slowing","volume":"32","author":"Insel","year":"2012","journal-title":"J Neurosci"}],"container-title":["Journal of Alzheimer's Disease"],"original-title":[],"link":[{"URL":"https:\/\/content.iospress.com\/download?id=10.3233\/JAD-201590","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T10:05:55Z","timestamp":1777370755000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.3233\/JAD-201590"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,15]]},"references-count":39,"journal-issue":{"issue":"4"},"URL":"https:\/\/doi.org\/10.3233\/jad-201590","relation":{},"ISSN":["1387-2877","1875-8908"],"issn-type":[{"value":"1387-2877","type":"print"},{"value":"1875-8908","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,15]]}}}