{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T03:40:19Z","timestamp":1793072419392,"version":"4.5.0"},"reference-count":70,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2024,9,14]],"date-time":"2024-09-14T00:00:00Z","timestamp":1726272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Acute brain injury (ABI) remains one of the leading causes of death and disability world-wide. Its treatment is challenging due to the heterogeneity of the mechanisms involved and the variability among individuals. This systematic review aims at evaluating the impact of anti-histone treatments on outcomes in ABI patients and experimental animals and defining the trend of nucleosome levels in biological samples post injury. We performed a search in Pubmed\/Medline and Embase databases for randomized controlled trials and cohort studies involving humans or experimental settings with various causes of ABI. We formulated the search using the PICO method, considering ABI patients or animal models as population (P), comparing pharmacological and non-pharmacological therapy targeting the nucleosome as Intervention (I) to standard of care or no treatment as Control (C). The outcome (O) was mortality or functional outcome in experimental animals and patients affected by ABI undergoing anti-NET treatments. We identified 28 studies from 1246 articles, of which 7 were experimental studies and 21 were human clinical studies. Among these studies, only four assessed the effect of anti-NET therapy on circulating markers. Three of them were preclinical and reported better outcome in the interventional arm compared to the control arm. All the studies observed a significant reduction in circulating NET-derived products. NETosis could be a target for new treatments. Monitoring NET markers in blood and cerebrospinal fluid might predict mortality and long-term outcomes. However, longitudinal studies and randomized controlled trials are warranted to fully evaluate their potential, as current evidence is limited.<\/jats:p>","DOI":"10.3390\/cells13181553","type":"journal-article","created":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T04:14:07Z","timestamp":1726460047000},"page":"1553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Targeting NETosis in Acute Brain Injury: A Systematic Review of Preclinical and Clinical Evidence"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7235-6215","authenticated-orcid":false,"given":"Marzia","family":"Savi","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20089 Milan, Italy"},{"name":"Department of Intensive Care, Erasme Hospital, Brussels University Hospital, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4962-7907","authenticated-orcid":false,"given":"Fuhong","family":"Su","sequence":"additional","affiliation":[{"name":"Laboratoire de Recherche Exp\u00e9rimentale des Soins Intensifs, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elda Diletta","family":"Sterchele","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Erasme Hospital, Brussels University Hospital, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Terapia Intensiva e del Dolore, Scuola di Anestesia Rianimazione, Universit\u00e0 degli Studi di Milano, 20089 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2062-465X","authenticated-orcid":false,"given":"Elisa Gouv\u00eaa","family":"Bogossian","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Erasme Hospital, Brussels University Hospital, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Laboratoire de Recherche Exp\u00e9rimentale des Soins Intensifs, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9768-0193","authenticated-orcid":false,"given":"Zo\u00e9","family":"Demailly","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Erasme Hospital, Brussels University Hospital, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Medical Intensive Care Unit, CHU Rouen, Normandie Universit\u00e9, F-76000 Rouen, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3447-6045","authenticated-orcid":false,"given":"Marta","family":"Baggiani","sequence":"additional","affiliation":[{"name":"Neurological Intensive Care Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico San Gerardo dei Tintori, 20900 Monza, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe Stefano","family":"Casu","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Erasme Hospital, Brussels University Hospital, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Laboratoire de Recherche Exp\u00e9rimentale des Soins Intensifs, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio Silvio","family":"Taccone","sequence":"additional","affiliation":[{"name":"Department of Intensive Care, Erasme Hospital, Brussels University Hospital, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"},{"name":"Laboratoire de Recherche Exp\u00e9rimentale des Soins Intensifs, Universit\u00e9 Libre de Bruxelles, 1070 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1001\/jamaneurol.2022.0114","article-title":"Traumatic Brain Injury in Older Adults\u2014A Public Health Perspective","volume":"79","author":"Waltzman","year":"2022","journal-title":"JAMA Neurol."},{"key":"ref_2","unstructured":"Peterson, A.B., Thomas, K.E., and Zhou, H. 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