{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:01:22Z","timestamp":1791856882392,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,12,7]],"date-time":"2015-12-07T00:00:00Z","timestamp":1449446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81271383"],"award-info":[{"award-number":["81271383"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81471245"],"award-info":[{"award-number":["81471245"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2016,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Sirtuin 2 (<jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>2) is a member of the sirtuin family of <jats:styled-content style=\"fixed-case\">NAD<\/jats:styled-content><jats:sup>+<\/jats:sup>\u2010dependent protein deacetylases. In recent years, <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>2 inhibition has emerged as a promising treatment for neurodegenerative diseases. However, to date, there is no evidence of a specific role for <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>2 in traumatic brain injury (<jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content>). We investigated the effects of <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>2 inhibition on experimental <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> using the controlled cortical impact (<jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content>) injury model. Adult male mice underwent <jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content> or sham surgery. A selective brain\u2010permeable <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>2 inhibitor, <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>\u20107, was administrated 30\u00a0min before injury. The volume of the brain edema lesion and the water content of the brain were significantly increased in mice treated with <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>\u20107 (20\u00a0mg\/kg), compared with the vehicle group, following <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05 at 1\u00a0day and <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05 at 3\u00a0days, respectively). Concomitantly, <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>\u20107 administration greatly worsened neurobehavioral deficits on days 3 and 7 after <jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content>. Furthermore, blood\u2013brain barrier disruption and matrix metalloproteinases (<jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>)\u20109 activity increased following <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>2 inhibition. <jats:styled-content style=\"fixed-case\">AK<\/jats:styled-content>\u20107 treatment increased <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content>\u2010induced microglial activation both <jats:italic>in\u00a0vivo<\/jats:italic> and <jats:italic>in\u00a0vitro<\/jats:italic>, accompanied by a large increase in the expression and release of inflammatory cytokines. Mechanistically, <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>2 inhibition increased both K310 acetylation and nuclear translocation of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB p65, leading to enhanced <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB activation and up\u2010regulation of its target genes, including aquaporin 4 (<jats:styled-content style=\"fixed-case\">AQP<\/jats:styled-content>4), <jats:styled-content style=\"fixed-case\">MMP<\/jats:styled-content>\u20109, and pro\u2010inflammatory cytokines. Together, these data demonstrate that <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>2 inhibition exacerbates <jats:styled-content style=\"fixed-case\">TBI<\/jats:styled-content> by increasing <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB p65 acetylation and activation. Our findings provide additional evidence of an anti\u2010inflammatory effect of <jats:styled-content style=\"fixed-case\">SIRT<\/jats:styled-content>2.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13423-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nSIRT2 is a member of the sirtuin family of NAD+\u2010dependent protein deacetylases. Our study suggests that the SIRT2 inhibitor AK\u20107 exacerbates traumatic brain injury (TBI) via a potential mechanism involving increased acetylation and nuclear translocation of NF\u2010\u03baB p65, resulting in up\u2010regulation of NF\u2010\u03baB target genes, including aquaporin 4 (AQP4), matrix metalloproteinase 9 (MMP\u20109), and pro\u2010inflammatory cytokines. Our findings provide additional evidence of an anti\u2010inflammatory effect of SIRT2.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13423","type":"journal-article","created":{"date-parts":[[2015,11,7]],"date-time":"2015-11-07T07:21:56Z","timestamp":1446880916000},"page":"581-593","source":"Crossref","is-referenced-by-count":119,"title":["<scp>SIRT<\/scp>2 inhibition exacerbates neuroinflammation and blood\u2013brain barrier disruption in experimental traumatic brain injury by enhancing <scp>NF<\/scp>\u2010\u03baB p65 acetylation and activation"],"prefix":"10.1111","volume":"136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4060-7830","authenticated-orcid":false,"given":"Fang","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Ming","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Yan","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Radiology Shanghai Jiao Tong University Affiliated Sixth People's Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Nie","sequence":"additional","affiliation":[{"name":"Neuroscience and Neuroengineering Research Center Med\u2010X Research Institute Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei\u2010Hai","family":"Ying","sequence":"additional","affiliation":[{"name":"Neuroscience and Neuroengineering Research Center Med\u2010X Research Institute Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng\u2010Li","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Shanghai Jiao Tong University Affiliated Sixth People's Hospital School of Medicine Shanghai Jiao Tong University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,12,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034805"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.18.7966-7975.2005"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000000305"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116919"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.06.053"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.11.001"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201402431"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0b013e328337f451"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3442-11.2012"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1238858"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10942"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.487736"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3293"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601758"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.06.005"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06630.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2014.06.135"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2013.03.032"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.10.153"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103573"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1940"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002924107"},{"key":"e_1_2_7_24_1","first-page":"608732","article-title":"Traumatic brain injury, microglia, and Beta amyloid","volume":"2012","author":"Mannix R. 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