{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T15:17:12Z","timestamp":1783351032503,"version":"3.54.6"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Augsburg","award":["2023-8660015"],"award-info":[{"award-number":["2023-8660015"]}]},{"name":"Universit\u00e4tsklinikum Augsburg"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurocrit Care"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Spontaneous intracerebral hemorrhage (ICH) is a subtype of stroke frequently resulting in severe disability. Secondary mechanisms after ICH include neuroinflammation and development of perihematomal edema. Neutrophil extracellular traps (NETs) mediate infection defense and are involved in disease processes affecting the nervous system, including immunothrombosis and blood\u2013brain barrier disruption. We aimed to assess NETs in ICH and their potential contribution to outcome measures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a prospective, single-center cohort study recruiting patients with ICH within 24\u00a0h after symptom onset and collected clinical, laboratory, imaging, and 3-month outcome data. NET components [citrullinated histone H3[H3Cit]\u2013DNA complexes and myeloperoxidase (MPO)\u2013DNA complexes, cell-free DNA (cfDNA)] and DNase activity were measured in plasma collected on admission, on day 2\/3, and on day 6 (\u00b1\u20091\u00a0day) after admission. We assessed ICH volume and perihematomal edema (PHE) semiquantitatively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We enrolled 50 patients with ICH (mean age 72\u00a0years) with mainly supratentorial ICH (86%), a median ICH volume of 16\u00a0ml [interquartile range (IQR) 5.8\u201338], and a median PHE volume of 11\u00a0ml (IQR 5\u201326). Compared with healthy controls, NETs were detectable in patients with ICH on admission at higher levels (H3Ccit-DNA,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001; cfDNA,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) together with lower DNase activity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.012). During the first 6\u00a0days after ICH, we observed an increase of NET components H3Cit\u2013DNA (baseline, median 6.0\u00a0ng\/ml [IQR 1.4\u20139.5] vs. day 6, 12.0\u00a0ng\/ml [IQR 5.7 vs. 19.0],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), MPO\u2013DNA (1.4\u00a0ng\/ml [IQR 0.59\u20132.2] vs. 2.6\u00a0ng\/ml [IQR 1.4\u20133.4],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and cfDNA (115\u00a0ng\/ml [IQR 106\u2013125] vs. 137\u00a0ng\/ml [IQR 127\u2013152],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), and a decline in DNase activity (median 85% [IQR 66\u2013102] vs. 66% [IQR 59\u201380],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). NET trajectories correlated with imaging outcomes (ICH volume, PHE volume) and clinical outcome measures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Increasing NETs and a decrease in DNase activity were observed during the early course after ICH onset and correlated with imaging and clinical outcomes. Future studies should evaluate the functional role of NETs in patients with ICH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12028-026-02577-1","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T14:50:34Z","timestamp":1783349434000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neutrophil Extracellular Traps in Patients with Intracerebral Hemorrhage"],"prefix":"10.1007","clinical-trial-number":[{"clinical-trial-number":"drks00025118","registry":"10.18810\/drks"}],"author":[{"given":"Leonie","family":"Gabor","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Zalghout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1026-6107","authenticated-orcid":false,"given":"Kimberly","family":"Martinod","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0305-0797","authenticated-orcid":false,"given":"Christoph J.","family":"Maurer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana","family":"Kremmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Culmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5016-9731","authenticated-orcid":false,"given":"Manuel","family":"Feisst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9641-0922","authenticated-orcid":false,"given":"Hauke","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"issue":"9675","key":"2577_CR1","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1016\/S0140-6736(09)60371-8","volume":"373","author":"AI Qureshi","year":"2009","unstructured":"Qureshi AI, Mendelow AD, Hanley DF. 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She is an inventor on granted US patent US10617742B2 for the methods for treating and preventing neutrophil-derived NET toxicity and thrombosis and granted US patent US11426405B2 on JAK\u2013STAT signaling inhibition preventing NET formation. All other authors declare that they have no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of Interest"}},{"value":"Institutional review board approval was obtained from the Ethics Committee of the Bavarian Medical Association before enrollment of patients (BL\u00c4K, EK 22098). Written informed consent for study participation was provided by each patient or their legally authorized representative. Conditional inclusion was possible for patients who were not able to consent initially. Consent was waived for patients who were not able to consent initially and who died during hospital stay.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval\/informed consent"}},{"value":"DRKS00025118, German Clinical Trials Register,\n                      \n                      .","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Clinical Trial registration"}},{"value":"The authors declare that no AI-assisted technologies were used in the production of the submitted work.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Artificial intelligence"}}]}}