{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T22:19:57Z","timestamp":1792016397946,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,12,21]],"date-time":"2011-12-21T00:00:00Z","timestamp":1324425600000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2011,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Cognitive decline accompanies acute illness and surgery, especially in the elderly. Surgery engages the innate immune system that launches a systemic inflammatory response that, if unchecked, can cause multiple organ dysfunction. We sought to understand the mechanisms whereby the brain is targeted by the inflammatory response and how this can be resolved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      C57BL\/6J,\n                      <jats:italic>\n                        Ccr2\n                        <jats:sup>RFP\/+<\/jats:sup>\n                        Cx3cr1\n                        <jats:sup>GFP\/+<\/jats:sup>\n                      <\/jats:italic>\n                      ,\n                      <jats:italic>\n                        Ikk\n                        <jats:sup>F\/F<\/jats:sup>\n                      <\/jats:italic>\n                      mice and\n                      <jats:italic>\n                        LysM\u2010Cre\/Ikk\n                        <jats:sup>F\/F<\/jats:sup>\n                      <\/jats:italic>\n                      mice underwent stabilized tibial fracture operation under analgesia and general anesthesia. Separate cohorts of mice were tested for systemic and hippocampal inflammation, integrity of the blood\u2013brain barrier (BBB), and cognition. The putative resolving effects of the cholinergic pathway on these postoperative responses were also studied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Peripheral surgery disrupts the BBB via release of tumor necrosis factor\u2010alpha (TNF\u03b1), which facilitates the migration of macrophages into the hippocampus. Macrophage\u2010specific deletion of Ikappa B kinase (IKK)\u03b2, a central coordinator of TNF\u03b1 signaling through activation of nuclear factor (NF) \u03baB, prevents BBB disruption and macrophage infiltration in the hippocampus following surgery. Activation of the \u03b17 subtype of nicotinic acetylcholine receptors, an endogenous inflammation\u2010resolving pathway, prevents TNF\u03b1\u2010induced NF\u2010\u03baB activation, macrophage migration into the hippocampus, and cognitive decline following surgery.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation:<\/jats:title>\n                    <jats:p>These data reveal the mechanisms for bidirectional communication between the brain and immune system following aseptic trauma. Pivotal molecular mechanisms can be targeted to prevent and\/or resolve postoperative neuroinflammation and cognitive decline. ANN NEUROL 2011;70:986\u2013995<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.22664","type":"journal-article","created":{"date-parts":[[2011,10,31]],"date-time":"2011-10-31T07:44:29Z","timestamp":1320047069000},"page":"986-995","source":"Crossref","is-referenced-by-count":523,"title":["Resolving postoperative neuroinflammation and cognitive decline"],"prefix":"10.1002","volume":"70","author":[{"given":"Niccol\u00f2","family":"Terrando","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars I.","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae","family":"Kyu Ryu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Monaco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Feldmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin","family":"Jonsson Fagerlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel F.","family":"Charo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Akassoglou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervyn","family":"Maze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,12,21]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2010.167"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.14.1753"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e318195b569"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature08780"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22082"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1014557107"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/35013070"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24177"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00240.2007"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013693"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1008942828960"},{"key":"e_1_2_7_13_2","first-page":"2190","article-title":"The autophagy\u2010related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice","volume":"118","author":"Pickford F","year":"2008","journal-title":"J Clin Invest"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0137-10.2010"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1819"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.psych.56.091103.070213"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2522-07.2007"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401030101"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni0302-221"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn230"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00434.x"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01339"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2566"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-5728(92)90087-2"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2927"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3242-07.2007"},{"key":"e_1_2_7_27_2","doi-asserted-by":"crossref","first-page":"206","DOI":"10.2310\/7290.2010.00042","article-title":"Superparamagnetic iron oxide\u2010enhanced magnetic resonance imaging of neuroinflammation in a rat model of radicular pain","volume":"10","author":"Thorek DL","year":"2011","journal-title":"Mol Imaging"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(95)93890-A"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1186\/1744-8069-6-74"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200603000-00005"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.9.5611"},{"key":"e_1_2_7_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.11.032"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2004.01988.x"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.174.6.1549"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2004.07.040"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201141550"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1018501108"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)07382-0"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7046051"},{"key":"e_1_2_7_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00540-011-1137-0"}],"container-title":["Annals of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fana.22664","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ana.22664","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,16]],"date-time":"2023-10-16T22:48:17Z","timestamp":1697496497000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ana.22664"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12]]},"references-count":39,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,12]]}},"alternative-id":["10.1002\/ana.22664"],"URL":"https:\/\/doi.org\/10.1002\/ana.22664","archive":["Portico"],"relation":{},"ISSN":["0364-5134","1531-8249"],"issn-type":[{"value":"0364-5134","type":"print"},{"value":"1531-8249","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,12]]}}}