{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T06:02:06Z","timestamp":1775714526730,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2019,10,5]],"date-time":"2019-10-05T00:00:00Z","timestamp":1570233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:p>\n                    Tuberculous meningitis (TBM) is the most lethal form of tuberculosis infection, characterized by a dysregulated immune response that frequently leads to neurologic injury and death despite the best available treatment. The mechanisms driving the inflammatory response in TBM are not well understood. To gain insights into these mechanisms, we used a lipid mediator\u2013profiling approach to investigate the regulation of a novel group of host protective mediators, termed specialized proresolving mediators (SPMs), in the cerebrospinal fluid (CSF) of adults with TBM. Herein, using CSF from patients enrolled into a randomized placebo\u2010controlled trial of adjunctive aspirin treatment, we found distinct lipid mediator profiles with increasing disease severity. These changes were linked with an up\u2010regulation of inflammatory eicosanoids in patients with severe TBM and a decrease in the production of a number of SPMs. CSF proresolving mediator concentrations were also associated with 80\u2010d survival. In survivors, we found a significant increase in proresolving mediator concentrations, including the lipoxygenase 5\u2010derived 13\u2010series resolvin (RvT)2, RvT4, and 15\u2010epi\u2010lipoxin B\n                    <jats:sub>4<\/jats:sub>\n                    , compared with those who died. Of note, treatment of patients with high\u2010dose aspirin led to a decrease in the concentrations of the prothrombic mediator thromboxane A\n                    <jats:sub>2<\/jats:sub>\n                    , reduced brain infarcts, and decreased death in patients with TBM. Together, these findings identify a CSF SPM signature that is associated with disease severity and 80\u2010d mortality in TBM.\u2014Colas, R. A., Nhat, L. T. H., Thuong N. T. T., G\u00f3mez, E. A., Ly, L., Thanh, H. H., Mai, N. T. H., Phu, N. H., Thwaites, G. E., Dalli, J. Proresolving mediator profiles in cerebrospinal fluid are linked with disease severity and outcome in adults with tuberculous meningitis. FASEB J. 33, 13028\u201313039 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201901590r","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T23:25:52Z","timestamp":1568071552000},"page":"13028-13039","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Proresolving mediator profiles in cerebrospinal fluid are linked with disease severity and outcome in adults with tuberculous meningitis"],"prefix":"10.1096","volume":"33","author":[{"given":"Romain A.","family":"Colas","sequence":"first","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Le Thanh Hoang","family":"Nhat","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen Thuy Thuong","family":"Thuong","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esteban A.","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy","family":"Ly","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai Hoang","family":"Thanh","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen Thi Hoang","family":"Mai","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nguyen Hoan","family":"Phu","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit Ho Chi Minh City Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy E.","family":"Thwaites","sequence":"additional","affiliation":[{"name":"Oxford University Clinical Research Unit Ho Chi Minh City Vietnam"},{"name":"Nuffield Department of Medicine Centre for Tropical Medicine and Global Health, University of Oxford Oxford United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesmond","family":"Dalli","sequence":"additional","affiliation":[{"name":"William Harvey Research Institute, Barts and The London School of Medicine and Dentistry"},{"name":"Centre for Inflammation and Therapeutic Innovation Queen Mary University of London London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,10,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.120"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix050"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(12)70264-5"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1507062"},{"key":"e_1_2_8_6_1","first-page":"CD002244","article-title":"Corticosteroids for managing tuberculous meningitis","volume":"4","author":"Prasad K.","year":"2016","journal-title":"Cochrane Database Syst. 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