{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:54:36Z","timestamp":1791510876093,"version":"4.3.4"},"reference-count":116,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T00:00:00Z","timestamp":1757289600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:p>Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating neurological disease, and one of the primary drivers of morbidity after aneurysm rupture is the phenomenon of delayed cerebral ischemia (DCI). Significant knowledge has been gained over the past two decades of the impact of neuroinflammation in DCI; and neutrophils are now believed to play a major role. There is significant human subject data showing the rise of neutrophil related inflammatory markers and neutrophil\u2019s association with poor outcome after aSAH, but as of yet no trials involving human subjects have been done specifically targeting neutrophils. There is however a growing body of evidence in animals models that targeting neutrophils, or their byproducts such as neutrophil extracellular traps improves outcomes. This review summarizes the available evidence of neutrophil\u2019s impact in both human subjects and animal models of aSAH and should serve as an impetuous to explore clinical trials in human subjects.<\/jats:p>","DOI":"10.1177\/0271678x251370858","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T09:52:50Z","timestamp":1757325170000},"page":"2269-2282","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["The role of neutrophils in vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: Is it time for a SAH clinical trial targeting neutrophils?"],"prefix":"10.1177","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1202-7249","authenticated-orcid":false,"given":"William W","family":"Wroe","sequence":"first","affiliation":[{"name":"The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussein A","family":"Zeineddine","sequence":"additional","affiliation":[{"name":"The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2902-5079","authenticated-orcid":false,"given":"Spiros L","family":"Blackburn","sequence":"additional","affiliation":[{"name":"The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9256-7973","authenticated-orcid":false,"given":"Jaroslaw","family":"Aronowski","sequence":"additional","affiliation":[{"name":"Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin W","family":"McBride","sequence":"additional","affiliation":[{"name":"The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70025-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/aes264"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.246"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.112.666693"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.3171\/2022.2.JNS212914"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3171\/2024.4.JNS232191"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/97.1.79"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2017.02.001"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/384342"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-019-00829-x"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-024-01242-z"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-1192-5_42"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-07447-6.00002-8"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.490128"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000124122.71702.64"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2016.11.010"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.116.013627"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.018120"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.034024"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.694996"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073636"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0680-x"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.118.021477"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.671098"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2021.105936"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1136\/neurintsurg-2019-014759"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2019.104631"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.3171\/2018.9.JNS181975"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S190477"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-021-01525-1"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.962760"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1080\/02688697.2017.1344615"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.1992.00400130135017"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2017.07.020"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.917987"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.2147\/IJGM.S323114"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/7458451"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-039860"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2022.03.027"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2020.12.084"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2023.107788"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-023-03433-x"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1629-7"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.1995.11740296"},{"issue":"1","key":"e_1_3_2_46_2","first-page":"141","article-title":"Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH","volume":"25","author":"Hendryk S","year":"2004","unstructured":"Hendryk S, Jarzab B, Josko J. Increase of the IL-1 beta and IL-6 levels in CSF in patients with vasospasm following aneurysmal SAH. Neuro Endocrinol Lett 2004; 25(1\u20132): 141\u2013147.","journal-title":"Neuro Endocrinol Lett"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1080\/01616412.1998.11740528"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-022-01001-y"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01078"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1998.89.4.0559"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2004.101.6.1030"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2021.577610"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-019-00871-9"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12028-009-9308-7"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40064-015-0970-2"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005743107"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01933-x"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200606027"},{"issue":"12","key":"e_1_3_2_60_2","first-page":"7413","article-title":"A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to","volume":"185","author":"Pilsczek FH","year":"2010","unstructured":"Pilsczek FH, Salina D, Poon KKH, et al. A novel mechanism of rapid nuclear neutrophil extracellular trap formation in response to Staphylococcus aureus. J Immunol 2010; 185(12): 7413\u20137425.","journal-title":"Staphylococcus aureus. J Immunol"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2009.96"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-022-01039-y"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232415823"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2011.1"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2016.05.029"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2021.724611"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-00591-7"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.766178"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-021-00909-1"},{"issue":"5","key":"e_1_3_2_70_2","article-title":"Neutrophil extracellular traps and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage","volume":"4","author":"Witsch J","year":"2022","unstructured":"Witsch J, Spalart V, Martinod K, et al. Neutrophil extracellular traps and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage. Crit Care Explor 2022; 4(5): E0692.","journal-title":"Crit Care Explor"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2024.1354224"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.123.320224"},{"key":"e_1_3_2_73_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-016-0513-3"},{"key":"e_1_3_2_74_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-018-0657-4"},{"key":"e_1_3_2_75_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-8-103"},{"key":"e_1_3_2_76_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-016-0485-3"},{"key":"e_1_3_2_77_2","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.228728"},{"key":"e_1_3_2_78_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0967-5868(99)90034-6"},{"key":"e_1_3_2_79_2","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.51.679"},{"key":"e_1_3_2_80_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1992.76.4.0571"},{"key":"e_1_3_2_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2010.10.016"},{"key":"e_1_3_2_82_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.02.007"},{"key":"e_1_3_2_83_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44906-9"},{"key":"e_1_3_2_84_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12975-022-01074-9"},{"key":"e_1_3_2_85_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2015.10.054"},{"key":"e_1_3_2_86_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.10.006"},{"key":"e_1_3_2_87_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2017.11.011"},{"key":"e_1_3_2_88_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.016705"},{"key":"e_1_3_2_89_2","doi-asserted-by":"publisher","DOI":"10.1093\/neuros\/nyaa495"},{"key":"e_1_3_2_90_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells10061510"},{"key":"e_1_3_2_91_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.033513"},{"key":"e_1_3_2_92_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.042308.113238"},{"key":"e_1_3_2_93_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.1.181"},{"key":"e_1_3_2_94_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.29.9.1930"},{"key":"e_1_3_2_95_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2004.101.1.0088"},{"key":"e_1_3_2_96_2","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2003.99.2.0376"},{"key":"e_1_3_2_97_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.surneu.2005.04.038"},{"key":"e_1_3_2_98_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.09.116"},{"key":"e_1_3_2_99_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200535300"},{"key":"e_1_3_2_100_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2015.01.047"},{"key":"e_1_3_2_101_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-023-01268-6"},{"issue":"3","key":"e_1_3_2_102_2","article-title":"Neutrophil extracellular traps in ischemic stroke thrombi are associated with poor clinical outcome","volume":"3","author":"Lapostolle A","year":"2023","unstructured":"Lapostolle A, Loyer C, Elhorany M, et al. Neutrophil extracellular traps in ischemic stroke thrombi are associated with poor clinical outcome. Stroke Vasc Interv Neurol 2023; 3(3): e000639.","journal-title":"Stroke Vasc Interv Neurol"},{"key":"e_1_3_2_103_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000009532"},{"key":"e_1_3_2_104_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.019896"},{"key":"e_1_3_2_105_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mvr.2023.104592"},{"key":"e_1_3_2_106_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.123.323897"},{"key":"e_1_3_2_107_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.124.047574"},{"key":"e_1_3_2_108_2","doi-asserted-by":"publisher","DOI":"10.18632\/aging.202993"},{"key":"e_1_3_2_109_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-21-4045"},{"key":"e_1_3_2_110_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700639"},{"key":"e_1_3_2_111_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.02.043"},{"key":"e_1_3_2_112_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.775267"},{"key":"e_1_3_2_113_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.121.035699"},{"key":"e_1_3_2_114_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25053007"},{"key":"e_1_3_2_115_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-84828-0_182"},{"key":"e_1_3_2_116_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-022-00845-6"},{"key":"e_1_3_2_117_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12113424"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X251370858","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X251370858","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X251370858","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:12:41Z","timestamp":1777493561000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X251370858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,8]]},"references-count":116,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1177\/0271678X251370858"],"URL":"https:\/\/doi.org\/10.1177\/0271678x251370858","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,8]]}}}