{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:58:04Z","timestamp":1790384284777,"version":"4.1.0"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>P2X7 participates in neuroinflammation underlying acute brain injury. In this study, we investigated the prognostic role of serum P2X7 in acute intracerebral hemorrhage (ICH).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This two-center observational analytic study enrolled 95 controls and 196 patients with acute supratentorial ICH. Serum P2X7 levels were measured at study entry in controls and at admission in all ICH patients, with serial measurements performed in a subgroup of 95 patients. Disease severity was assessed using the National Institutes of Health Stroke Scale (NIHSS) and hematoma volume. The primary neurological functional outcome was assessed using the modified Rankin Scale (mRS) at 6\u202fmonths post-ICH. Multivariable analysis was performed to model the associations between P2X7 levels, disease severity, and final functional prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In patients with ICH, serum P2X7 levels were markedly elevated upon admission, peaked at day 3, and gradually declined through to day 10. Patient serum P2X7 levels remained notably higher than those of controls throughout the 10-day period. Serum P2X7 levels were linearly correlated with NIHSS scores, hematoma volume, mRS scores, and poor prognosis (mRS 3\u20136) under restricted cubic spline analysis. These associations persisted after adjustment for potential confounding factors. Sensitivity analyses, subgroup analyses, and receiver operating characteristic (ROC) curve analysis consistently demonstrated that serum P2X7 levels were robustly associated with poor prognosis. Applying calibration curve, decision curve, ROC curve, and model improvement rate analyses, a combined model integrating serum P2X7 levels, NIHSS scores, and hematoma volume demonstrated strong performance. Furthermore, serum P2X7 levels partially mediated the correlations of NIHSS scores and hematoma volume with poor prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Increased serum P2X7 levels after ICH are markedly associated with disease severity and poor prognosis. Moreover, P2X7 may partially mediate the relationship between ICH severity and prognosis, underscoring its potential as a prognostic biomarker.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2025.1696189","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T06:30:54Z","timestamp":1768372254000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum P2X7 as a prognostic biomarker in acute supratentorial intracerebral hemorrhage: a two-center observational study"],"prefix":"10.3389","volume":"16","author":[{"given":"Xinle","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Zhejiang Rongjun Hospital","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Shan","sequence":"additional","affiliation":[{"name":"The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiancheng","family":"Lu","sequence":"additional","affiliation":[{"name":"The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boren","family":"Zheng","sequence":"additional","affiliation":[{"name":"The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiao","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Affiliated Hangzhou First People's Hospital, Westlake University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Zhejiang Rongjun Hospital","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Zhejiang Rongjun Hospital","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guozheng","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Zhejiang Rongjun Hospital","place":["Jiaxing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,14]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"123329","DOI":"10.1016\/j.jns.2024.123329","article-title":"Recent and future advances in intracerebral hemorrhage","volume":"467","author":"Puy","year":"2024","journal-title":"J Neurol Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1056\/NEJMra2201449","article-title":"Spontaneous intracerebral hemorrhage","volume":"387","author":"Sheth","year":"2022","journal-title":"N Engl J Med"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1080\/14737175.2019.1623671","article-title":"Intracerebral hemorrhage: an update on diagnosis and treatment","volume":"19","author":"Hostettler","year":"2019","journal-title":"Expert Rev Neurother"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000542566","article-title":"Intracerebral hemorrhage","volume":"15","author":"Lee","year":"2025","journal-title":"Cerebrovasc Dis Extra"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1161\/CIRCRESAHA.121.319949","article-title":"Cerebral hemorrhage: pathophysiology, treatment, and future directions","volume":"130","author":"Magid-Bernstein","year":"2022","journal-title":"Circ Res"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1161\/STROKEAHA.124.046130","article-title":"Pathophysiology of intracerebral hemorrhage: recovery trajectories","volume":"56","author":"Mai","year":"2025","journal-title":"Stroke"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1177\/17474930241292022","article-title":"Stroke severity and outcomes in patients with intracerebral hemorrhage on anticoagulants and antiplatelet agents: an analysis from the Japan stroke data Bank","volume":"20","author":"Arakaki","year":"2025","journal-title":"Int J Stroke"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1159\/000543362","article-title":"Functional outcome prediction in Japanese patients with nonsurgical intracerebral hemorrhage: the FSR ICH score","volume":"54","author":"Kiyohara","year":"2025","journal-title":"Cerebrovasc Dis"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"913926","DOI":"10.3389\/fneur.2022.913926","article-title":"Plasma PRPC levels correlate with severity and prognosis of intracerebral hemorrhage","volume":"13","author":"Wu","year":"2022","journal-title":"Front Neurol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.cca.2022.11.004","article-title":"\u0391-MSH as a potential biomarker of severity and prognosis after intracerebral hemorrhage: a prospective cohort study","volume":"538","author":"Hu","year":"2023","journal-title":"Clin Chim Acta"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.jphys.2013.12.012","article-title":"National Institutes of Health stroke scale (NIHSS)","volume":"60","author":"Kwah","year":"2014","journal-title":"J Physiother"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e70424","DOI":"10.1002\/brb3.70424","article-title":"Evaluation of prognostic implication of serum mixed lineage kinase domain-like protein in acute primary supratentorial intracerebral hemorrhage: a multicenter prospective cohort study","volume":"15","author":"Ma","year":"2025","journal-title":"Brain Behav"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/s12028-016-0276-4","article-title":"Intracerebral hemorrhage location and functional outcomes of patients: a systematic literature review and meta-analysis","volume":"25","author":"Sreekrishnan","year":"2016","journal-title":"Neurocrit Care"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"946","DOI":"10.1177\/15459683211041314","article-title":"Prognostic utility of serum biomarkers in intracerebral hemorrhage: a systematic review","volume":"35","author":"Troiani","year":"2021","journal-title":"Neurorehabil Neural Repair"},{"key":"ref15","first-page":"3000605211009689","article-title":"Serum glucose and potassium ratio as a predictive factor for prognosis of acute intracerebral hemorrhage","volume-title":"J Int Med Res","author":"Wu","year":"2021"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.cca.2022.06.018","article-title":"Role of plasma apo-J as a biomarker of severity and outcome after intracerebral hemorrhage: a prospective and cohort study","volume":"533","author":"Wu","year":"2022","journal-title":"Clin Chim Acta"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1007\/s00109-017-1545-1","article-title":"Purinergic signaling during intestinal inflammation","volume":"95","author":"Longhi","year":"2017","journal-title":"J Mol Med (Berl)"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"2770","DOI":"10.1093\/rheumatology\/keab859","article-title":"Purinergic signalling in systemic sclerosis","volume":"61","author":"H\u00f6ppner","year":"2022","journal-title":"Rheumatology (Oxford)"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.neuropharm.2015.05.005","article-title":"Purinergic signaling in retinal degeneration and regeneration","volume":"104","author":"Reichenbach","year":"2016","journal-title":"Neuropharmacology"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/s0014-2999(02)01848-4","article-title":"Extracellular ATP and P2X7 receptors in neurodegeneration","volume":"447","author":"Le Feuvre","year":"2002","journal-title":"Eur J Pharmacol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.brainres.2006.03.040","article-title":"P2X7 receptor immunoreactive profile confined to resting and activated microglia in the epileptic brain","volume":"1089","author":"Rappold","year":"2006","journal-title":"Brain Res"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"106229","DOI":"10.1016\/j.nbd.2023.106229","article-title":"Purinergic receptors in cognitive disturbances","volume":"185","author":"Illes","year":"2023","journal-title":"Neurobiol Dis"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1007\/s12264-013-1338-7","article-title":"P2X(7) receptors in cerebral ischemia","volume":"29","author":"Bai","year":"2013","journal-title":"Neurosci Bull"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1016\/j.arr.2015.10.001","article-title":"Emerging role of P2X7 receptors in CNS health and disease","volume":"24","author":"Tewari","year":"2015","journal-title":"Ageing Res Rev"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.pneurobio.2006.03.007","article-title":"P2X7 receptors in the nervous system","volume":"78","author":"Sperl\u00e1gh","year":"2006","journal-title":"Prog Neurobiol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.neuropharm.2017.09.030","article-title":"Ethanol differentially modulates P2X4 and P2X7 receptor activity and function in BV2 microglial cells","volume":"128","author":"Asatryan","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1753","DOI":"10.1016\/j.biocel.2010.06.021","article-title":"Microglia: proliferation and activation driven by the P2X7 receptor","volume":"42","author":"Monif","year":"2010","journal-title":"Int J Biochem Cell Biol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1080\/14728222.2023.2258281","article-title":"The neuroinflammatory astrocytic P2X7 receptor: Alzheimer's disease, ischemic brain injury, and epileptic state","volume":"27","author":"Ahn","year":"2023","journal-title":"Expert Opin Ther Targets"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"e41229","DOI":"10.1371\/journal.pone.0041229","article-title":"Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice","volume":"7","author":"Kimbler","year":"2012","journal-title":"PLoS One"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.4103\/1673-5374.303036","article-title":"P2X7 receptor activation aggravates NADPH oxidase 2-induced oxidative stress after intracerebral hemorrhage","volume":"16","author":"Deng","year":"2021","journal-title":"Neural Regen Res"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1097\/01.WCB.0000048519.34839.97","article-title":"Role of P2X7 receptors in ischemic and excitotoxic brain injury in vivo","volume":"23","author":"Le Feuvre","year":"2003","journal-title":"J Cereb Blood Flow Metab"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1007\/s11064-017-2257-1","article-title":"P2X7 participates in intracerebral hemorrhage-induced secondary brain injury in rats via MAPKs signaling pathways","volume":"42","author":"Wen","year":"2017","journal-title":"Neurochem Res"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1007\/s11302-017-9579-y","article-title":"Inhibition of P2X7 receptors improves outcomes after traumatic brain injury in rats","volume":"13","author":"Liu","year":"2017","journal-title":"Purinergic Signal"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1002\/med.21952","article-title":"Leveraging the ATP-P2X7 receptor signalling axis to alleviate traumatic CNS damage and related complications","volume":"43","author":"Yin","year":"2023","journal-title":"Med Res Rev"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.7150\/thno.97254","article-title":"P2X7R antagonism suppresses long-lasting brain hyperexcitability following traumatic brain injury in mice","volume":"15","author":"Alves","year":"2025","journal-title":"Theranostics"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"378","DOI":"10.3892\/etm.2023.12077","article-title":"Inhibition of P2X4 and P2X7 receptors improves histological and behavioral outcomes after experimental traumatic brain injury in rats","volume":"26","author":"Kobayashi","year":"2023","journal-title":"Exp Ther Med"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1186\/s12974-015-0409-2","article-title":"P2X7R blockade prevents NLRP3 inflammasome activation and brain injury in a rat model of intracerebral hemorrhage: involvement of peroxynitrite","volume":"12","author":"Feng","year":"2015","journal-title":"J Neuroinflammation"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1016\/j.nbd.2011.12.014","article-title":"P2X7 receptor blockade prevents ATP excitotoxicity in neurons and reduces brain damage after ischemia","volume":"45","author":"Arbeloa","year":"2012","journal-title":"Neurobiol Dis"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1007\/s11302-013-9379-y","article-title":"Block of P2X7 receptors could partly reverse the delayed neuronal death in area CA1 of the hippocampus after transient global cerebral ischemia","volume":"9","author":"Yu","year":"2013","journal-title":"Purinergic Signal"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1007\/s12035-022-03092-y","article-title":"Blocking P2RX7 attenuates ferroptosis in endothelium and reduces HG-induced hemorrhagic transformation after MCAO by inhibiting ERK1\/2 and P53 signaling pathways","volume":"60","author":"Liu","year":"2023","journal-title":"Mol Neurobiol"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"23286","DOI":"10.1038\/srep23286","article-title":"P2X7 receptor suppression preserves blood-brain barrier through inhibiting RhoA activation after experimental intracerebral hemorrhage in rats","volume":"6","author":"Zhao","year":"2016","journal-title":"Sci Rep"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"e466","DOI":"10.1097\/CCM.0b013e31829a8246","article-title":"P2X7 receptor antagonism inhibits p38 mitogen-activated protein kinase activation and ameliorates neuronal apoptosis after subarachnoid hemorrhage in rats","volume":"41","author":"Chen","year":"2013","journal-title":"Crit Care Med"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"114207","DOI":"10.1016\/j.expneurol.2022.114207","article-title":"P2X7 receptor as a potential therapeutic target for perinatal brain injury associated with preterm birth","volume":"357","author":"Zucker","year":"2022","journal-title":"Exp Neurol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"92","DOI":"10.3389\/fnmol.2020.00092","article-title":"P2X7 receptors as a therapeutic target in cerebrovascular diseases","volume":"13","author":"Cisneros-Mejorado","year":"2020","journal-title":"Front Mol Neurosci"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"237","DOI":"10.3389\/fncel.2013.00237","article-title":"P2X receptors as targets for the treatment of status epilepticus","volume":"7","author":"Henshall","year":"2013","journal-title":"Front Cell Neurosci"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"617036","DOI":"10.3389\/fncel.2021.617036","article-title":"P2X7 receptors in neurodegeneration: potential therapeutic applications from basic to clinical approaches","volume":"15","author":"Territo","year":"2021","journal-title":"Front Cell Neurosci"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1345625","DOI":"10.3389\/fimmu.2024.1345625","article-title":"Role and therapeutic targets of P2X7 receptors in neurodegenerative diseases","volume":"15","author":"Zheng","year":"2024","journal-title":"Front Immunol"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1161\/01.str.27.8.1304","article-title":"The ABCs of measuring intracerebral hemorrhage volumes","volume":"27","author":"Kothari","year":"1996","journal-title":"Stroke"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"e00294720","DOI":"10.1590\/0102-311X00294720","article-title":"On the use of the E-value for sensitivity analysis in epidemiologic studies","volume":"37","author":"Vale","year":"2021","journal-title":"Cad Saude Publica"},{"key":"ref50","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1002\/sim.3841","article-title":"Dose-response analyses using restricted cubic spline functions in public health research","volume":"29","author":"Desquilbet","year":"2010","journal-title":"Stat Med"},{"key":"ref51","first-page":"109","article-title":"Interaction, subgroup analysis and sample size","volume":"148","author":"Cuzick","year":"1999","journal-title":"IARC Sci Publ"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"558","DOI":"10.4097\/kja.19087","article-title":"Multicollinearity and misleading statistical results","volume":"72","author":"Kim","year":"2019","journal-title":"Korean J Anesthesiol"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1002\/sim.4348","article-title":"Novel metrics for evaluating improvement in discrimination: net reclassification and integrated discrimination improvement for normal variables and nested models","volume":"31","author":"Pencina","year":"2012","journal-title":"Stat Med"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"681","DOI":"10.3238\/arztebl.m2023.0175","article-title":"Mediation analysis in medical research","volume":"120","author":"T\u00f6nnies","year":"2023","journal-title":"Dtsch Arztebl Int"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s11302-012-9305-8","article-title":"ATP synthesis and storage","volume":"8","author":"Bonora","year":"2012","journal-title":"Purinergic Signal"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1097\/CCM.0000000000001603","article-title":"The role of extracellular adenosine triphosphate in ischemic organ injury","volume":"44","author":"Zhao","year":"2016","journal-title":"Crit Care Med"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.immuni.2017.06.020","article-title":"The P2X7 receptor in infection and inflammation","volume":"47","author":"Di Virgilio","year":"2017","journal-title":"Immunity"},{"key":"ref58","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1007\/5584_2017_59","article-title":"The P2X7 receptor","volume":"1051","author":"Sluyter","year":"2017","journal-title":"Adv Exp Med Biol"},{"key":"ref59","doi-asserted-by":"publisher","first-page":"e14853","DOI":"10.1111\/cns.14853","article-title":"Immune-mediated disruption of the blood-brain barrier after intracerebral hemorrhage: insights and potential therapeutic targets","volume":"30","author":"Jia","year":"2024","journal-title":"CNS Neurosci Ther"},{"key":"ref60","first-page":"193","article-title":"Effects of various inducers on the expression of P2X7 receptor in human peripheral blood mononuclear cells","volume":"57","author":"Zhang","year":"2005","journal-title":"Sheng Li Xue Bao"},{"key":"ref61","first-page":"779","article-title":"Expression of purinergic P2X7 receptors in subpopulations of peripheral blood mononuclear cells in early-stage of chronic kidney disease","volume":"68","author":"Lajdova","year":"2017","journal-title":"J Physiol Pharmacol"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"489","DOI":"10.17219\/acem\/145852","article-title":"Association between systemic inflammatory response syndrome and hematoma expansion in intracerebral hemorrhage","volume":"31","author":"Zhu","year":"2022","journal-title":"Adv Clin Exp Med"},{"key":"ref63","doi-asserted-by":"publisher","first-page":"e428","DOI":"10.1212\/NXI.0000000000000428","article-title":"Systemic inflammatory response syndrome, infection, and outcome in intracerebral hemorrhage","volume":"5","author":"Boehme","year":"2017","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"ref64","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1007\/s12028-016-0255-9","article-title":"Systemic inflammatory response syndrome and outcomes in intracerebral hemorrhage","volume":"25","author":"Boehme","year":"2016","journal-title":"Neurocrit Care"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3171\/foc.2007.22.5.7","article-title":"Brain edema after intracerebral hemorrhage: mechanisms, treatment options, management strategies, and operative indications","volume":"22","author":"Thiex","year":"2007","journal-title":"Neurosurg Focus"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1696189\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T06:30:55Z","timestamp":1768372255000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1696189\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,14]]},"references-count":65,"alternative-id":["10.3389\/fneur.2025.1696189"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1696189","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,14]]},"article-number":"1696189"}}