{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:04:20Z","timestamp":1788289460163,"version":"build-2803163510"},"reference-count":87,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":40,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32300821"],"award-info":[{"award-number":["32300821"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100013061","name":"Jilin Scientific and Technological Development Program","doi-asserted-by":"crossref","award":["20240402038GH"],"award-info":[{"award-number":["20240402038GH"]}],"id":[{"id":"10.13039\/501100013061","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["2023M741353"],"award-info":[{"award-number":["2023M741353"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neuroinflammation"],"DOI":"10.1186\/s12974-026-03778-3","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T04:35:27Z","timestamp":1774499727000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ginsenoside Rg2 attenuates secondary brain injury following intracerebral hemorrhage by inhibiting NLRP3-mediated pyroptosis"],"prefix":"10.1186","volume":"23","author":[{"given":"Han","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenwen","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huifeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenli","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunfang","family":"Zuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huali","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Dityatev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"key":"3778_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.103880","volume":"76","author":"M Zille","year":"2022","unstructured":"Zille M, Farr TD, Keep RF, R\u00f6mer C, Xi G, Boltze J. Novel targets, treatments, and advanced models for intracerebral haemorrhage. EBioMedicine. 2022;76:103880.","journal-title":"EBioMedicine"},{"key":"3778_CR2","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1136\/svn-2020-000334","volume":"5","author":"Q Bai","year":"2020","unstructured":"Bai Q, Sheng Z, Liu Y, Zhang R, Yong VW, Xue M. Intracerebral haemorrhage: from clinical settings to animal models. Stroke Vasc Neurol. 2020;5:388\u201395.","journal-title":"Stroke Vasc Neurol"},{"key":"3778_CR3","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1016\/S1474-4422(24)00369-7","volume":"23","author":"VL Feigin","year":"2024","unstructured":"Feigin VL, Abate MD, Abate YH, Abd ElHafeez S, Abd-Allah F, Abdelalim A, et al. Global, regional, and national burden of stroke and its risk factors, 1990\u20132021: a systematic analysis for the Global Burden of Disease Study 2021. The Lancet Neurology. 2024;23:973\u20131003.","journal-title":"The Lancet Neurology"},{"key":"3778_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.101180","volume":"49","author":"A Wolsink","year":"2025","unstructured":"Wolsink A, Cliteur MP, van Asch CJ, Boogaarts HD, Dammers R, Hannink G, et al. Incidence, case fatality, and functional outcome of intracerebral haemorrhage, according to age, sex, and country income level: a systematic review and meta-analysis. Lancet Reg Health Eur. 2025;49:101180.","journal-title":"Lancet Reg Health Eur"},{"key":"3778_CR5","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/S1474-4422(12)70104-7","volume":"11","author":"RF Keep","year":"2012","unstructured":"Keep RF, Hua Y, Xi G. Intracerebral haemorrhage: mechanisms of injury and therapeutic targets. Lancet Neurol. 2012;11:720\u201331.","journal-title":"Lancet Neurol"},{"key":"3778_CR6","doi-asserted-by":"publisher","first-page":"11382","DOI":"10.1007\/s12035-025-04950-1","volume":"62","author":"Y Fang","year":"2025","unstructured":"Fang Y, Sadike D, Jiang N, Xu Y, Wang Y, Liu Y, et al. TREK- 1 Ameliorates Secondary Brain Injury by Regulating Inflammatory Microenvironment via CX3 CL1-CX3 CR1 Pathway After Intracerebral Hemorrhage. Mol Neurobiol. 2025;62:11382\u2013402.","journal-title":"Mol Neurobiol"},{"key":"3778_CR7","doi-asserted-by":"crossref","unstructured":"Puy L, Parry-Jones\u00a0AR, Sandset\u00a0EC, Dowlatshahi\u00a0D, Ziai\u00a0W, Cordonnier\u00a0C. Intracerebral haemorrhage. Nat Rev Dis Primers. 2023; 9:14","DOI":"10.1038\/s41572-023-00424-7"},{"key":"3778_CR8","doi-asserted-by":"publisher","first-page":"1589","DOI":"10.1056\/NEJMra2201449","volume":"387","author":"N Sheth Kevin","year":"2022","unstructured":"Sheth Kevin N. Spontaneous Intracerebral Hemorrhage. N Engl J Med. 2022;387:1589\u201396.","journal-title":"N Engl J Med"},{"key":"3778_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105948","volume":"176","author":"Y Wan","year":"2023","unstructured":"Wan Y, Holste KG, Hua Y, Keep RF, Xi G. Brain edema formation and therapy after intracerebral hemorrhage. Neurobiol Dis. 2023;176:105948.","journal-title":"Neurobiol Dis"},{"key":"3778_CR10","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.pneurobio.2010.08.001","volume":"92","author":"J Wang","year":"2010","unstructured":"Wang J. Preclinical and clinical research on inflammation after intracerebral hemorrhage. Prog Neurobiol. 2010;92:463\u201377.","journal-title":"Prog Neurobiol"},{"key":"3778_CR11","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01588-0","volume":"8","author":"C Gao","year":"2023","unstructured":"Gao C, Jiang J, Tan Y, Chen S. Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets. Signal Transduct Target Ther. 2023;8:359.","journal-title":"Signal Transduct Target Ther"},{"key":"3778_CR12","doi-asserted-by":"publisher","first-page":"29","DOI":"10.5853\/jos.2019.02236","volume":"22","author":"C Tschoe","year":"2020","unstructured":"Tschoe C, Bushnell CD, Duncan PW, Alexander-Miller MA, Wolfe SQ. Neuroinflammation after intracerebral hemorrhage and potential therapeutic targets. J Stroke. 2020;22:29\u201346.","journal-title":"J Stroke"},{"key":"3778_CR13","doi-asserted-by":"publisher","first-page":"5130","DOI":"10.1007\/s12035-020-02082-2","volume":"57","author":"L Xiao","year":"2020","unstructured":"Xiao L, Zheng H, Li J, Wang Q, Sun H. Neuroinflammation mediated by NLRP3 inflammasome after intracerebral hemorrhage and potential therapeutic targets. Mol Neurobiol. 2020;57:5130\u201349.","journal-title":"Mol Neurobiol"},{"key":"3778_CR14","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.tins.2019.11.005","volume":"43","author":"BA McKenzie","year":"2020","unstructured":"McKenzie BA, Dixit VM, Power C. Fiery cell death: pyroptosis in the central nervous system. Trends Neurosci. 2020;43:55\u201373.","journal-title":"Trends Neurosci"},{"key":"3778_CR15","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102960","volume":"68","author":"C Liu","year":"2023","unstructured":"Liu C, Yao K, Tian Q, Guo Y, Wang G, He P, et al. CXCR4-BTK axis mediate pyroptosis and lipid peroxidation in early brain injury after subarachnoid hemorrhage via NLRP3 inflammasome and NF-\u03baB pathway. Redox Biol. 2023;68:102960.","journal-title":"Redox Biol"},{"key":"3778_CR16","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1186\/s12974-022-02558-z","volume":"19","author":"P Jin","year":"2022","unstructured":"Jin P, Qi D, Cui Y, Lenahan C, Zhang JH, Tao X, et al. Aprepitant attenuates NLRC4-dependent neuronal pyroptosis via NK1R\/PKC\u03b4 pathway in a mouse model of intracerebral hemorrhage. J Neuroinflammation. 2022;19:198.","journal-title":"J Neuroinflammation"},{"key":"3778_CR17","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1161\/STROKEAHA.123.043391","volume":"54","author":"M Yang","year":"2023","unstructured":"Yang M, Deng S, Jiang J, Tian M, Xiao L, Gong Y. Oxytocin improves intracerebral hemorrhage outcomes by suppressing neuronal pyroptosis and mitochondrial fission. Stroke. 2023;54:1888\u2013900.","journal-title":"Stroke"},{"key":"3778_CR18","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nri.2016.58","volume":"16","author":"P Broz","year":"2016","unstructured":"Broz P, Dixit VM. Inflammasomes: mechanism of assembly, regulation and signalling. Nat Rev Immunol. 2016;16:407\u201320.","journal-title":"Nat Rev Immunol"},{"key":"3778_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2024.114950","volume":"382","author":"F Gu","year":"2024","unstructured":"Gu F, Wang Z, Ding H, Tao X, Zhang J, Dai K, et al. Microglial mitochondrial DNA release contributes to neuroinflammation after intracerebral hemorrhage through activating AIM2 inflammasome. Exp Neurol. 2024;382:114950.","journal-title":"Exp Neurol"},{"key":"3778_CR20","doi-asserted-by":"publisher","first-page":"4050","DOI":"10.1073\/pnas.1419090112","volume":"112","author":"A Denes","year":"2015","unstructured":"Denes A, Coutts G, L\u00e9n\u00e1rt N, Cruickshank SM, Pelegrin P, Skinner J, et al. AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3. Proc Natl Acad Sci U S A. 2015;112:4050\u20135.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3778_CR21","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02207-x","volume":"18","author":"WS Dodd","year":"2021","unstructured":"Dodd WS, Noda I, Martinez M, Hosaka K, Hoh BL. Nlrp3 inhibition attenuates early brain injury and delayed cerebral vasospasm after subarachnoid hemorrhage. J Neuroinflammation. 2021;18:163.","journal-title":"J Neuroinflammation"},{"key":"3778_CR22","doi-asserted-by":"publisher","DOI":"10.3390\/cells12182327","author":"CR Harrell","year":"2023","unstructured":"Harrell CR, Djonov V, Antonijevic A, Volarevic V. Nlrp3 inflammasome as a potentially new therapeutic target of mesenchymal stem cells and their exosomes in the treatment of inflammatory eye diseases. Cells. 2023.","journal-title":"Cells"},{"key":"3778_CR23","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1146\/annurev-pathmechdis-012419-032847","volume":"15","author":"J Zindel","year":"2020","unstructured":"Zindel J, Kubes P. DAMPs, PAMPs, and LAMPs in immunity and sterile inflammation. Annu Rev Pathol. 2020;15:493\u2013518.","journal-title":"Annu Rev Pathol"},{"key":"3778_CR24","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/s41418-018-0124-5","volume":"26","author":"E Lee","year":"2019","unstructured":"Lee E, Hwang I, Park S, Hong S, Hwang B, Cho Y, et al. MPTP-driven Nlrp3 inflammasome activation in microglia plays a central role in dopaminergic neurodegeneration. Cell Death Differ. 2019;26:213\u201328.","journal-title":"Cell Death Differ"},{"key":"3778_CR25","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1016\/j.tips.2022.04.003","volume":"43","author":"RC Coll","year":"2022","unstructured":"Coll RC, Schroder K, Pelegr\u00edn P. Nlrp3 and pyroptosis blockers for treating inflammatory diseases. Trends Pharmacol Sci. 2022;43:653\u201368.","journal-title":"Trends Pharmacol Sci"},{"key":"3778_CR26","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.bbi.2024.03.038","volume":"119","author":"X Zhang","year":"2024","unstructured":"Zhang X, Zhang Y, Wang B, Xie C, Wang J, Fang R, et al. Pyroptosis-mediator GSDMD promotes Parkinson\u2019s disease pathology via microglial activation and dopaminergic neuronal death. Brain Behav Immun. 2024;119:129\u201345.","journal-title":"Brain Behav Immun"},{"key":"3778_CR27","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1038\/nm.3806","volume":"21","author":"RC Coll","year":"2015","unstructured":"Coll RC, Robertson AA, Chae JJ, Higgins SC, Mu\u00f1oz-Planillo R, Inserra MC, et al. A small-molecule inhibitor of the Nlrp3 inflammasome for the treatment of inflammatory diseases. Nat Med. 2015;21:248\u201355.","journal-title":"Nat Med"},{"key":"3778_CR28","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1038\/s41401-021-00664-x","volume":"42","author":"LL Kong","year":"2021","unstructured":"Kong LL, Gao L, Wang KX, Liu NN, Liu CD, Ma GD, et al. Pinocembrin attenuates hemorrhagic transformation after delayed t-PA treatment in thromboembolic stroke rats by regulating endogenous metabolites. Acta Pharmacol Sin. 2021;42:1223\u201334.","journal-title":"Acta Pharmacol Sin"},{"key":"3778_CR29","doi-asserted-by":"publisher","DOI":"10.1186\/s12951-024-02368-w","volume":"22","author":"X Tang","year":"2024","unstructured":"Tang X, Yang X, Yu Y, Wu M, Li Y, Zhang Z, et al. Carbon quantum dots of ginsenoside Rb1 for application in a mouse model of intracerebral hemorrhage. J Nanobiotechnology. 2024;22:125.","journal-title":"J Nanobiotechnology"},{"key":"3778_CR30","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.jep.2007.10.026","volume":"115","author":"G Zhang","year":"2008","unstructured":"Zhang G, Liu A, Zhou Y, San X, Jin T, Jin Y. Panax ginseng ginsenoside-Rg2 protects memory impairment via anti-apoptosis in a rat model with vascular dementia. J Ethnopharmacol. 2008;115:441\u20138.","journal-title":"J Ethnopharmacol"},{"key":"3778_CR31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.113466","volume":"266","author":"J Cui","year":"2021","unstructured":"Cui J, Shan R, Cao Y, Zhou Y, Liu C, Fan Y. Protective effects of ginsenoside Rg2 against memory impairment and neuronal death induced by A\u03b225-35 in rats. J Ethnopharmacol. 2021;266:113466.","journal-title":"J Ethnopharmacol"},{"key":"3778_CR32","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2024.156063","volume":"135","author":"YW Lu","year":"2024","unstructured":"Lu YW, Wang YJ, Wang Z, Ren S, Gong XJ, Hu JN, et al. Ginsenoside Rg2 alleviates astrocyte inflammation and ameliorates the permeability of the Alzheimer\u2019s disease related blood-brain barrier. Phytomedicine. 2024;135:156063.","journal-title":"Phytomedicine"},{"key":"3778_CR33","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154341","volume":"104","author":"JJ Zhang","year":"2022","unstructured":"Zhang JJ, Chen KC, Zhou Y, Wei H, Qi MH, Wang Z, et al. Evaluating the effects of mitochondrial autophagy flux on ginsenoside Rg2 for delaying D-galactose induced brain aging in mice. Phytomedicine. 2022;104:154341.","journal-title":"Phytomedicine"},{"key":"3778_CR34","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.jgr.2015.04.006","volume":"40","author":"N Li","year":"2016","unstructured":"Li N, Liu Y, Li W, Zhou L, Li Q, Wang X, et al. A UPLC\/MS-based metabolomics investigation of the protective effect of ginsenosides Rg1 and Rg2 in mice with Alzheimer\u2019s disease. J Ginseng Res. 2016;40:9\u201317.","journal-title":"J Ginseng Res"},{"key":"3778_CR35","doi-asserted-by":"publisher","DOI":"10.3390\/cells7120270","author":"W Xie","year":"2018","unstructured":"Xie W, Zhou P, Sun Y, Meng X, Dai Z, Sun G, et al. Protective effects and target network analysis of Ginsenoside Rg1 in cerebral ischemia and reperfusion injury: a comprehensive overview of experimental studies. Cells. 2018.","journal-title":"Cells"},{"key":"3778_CR36","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1142\/S0192415X2550034X","volume":"53","author":"K Li","year":"2025","unstructured":"Li K, Wang YJ, Wei K, Li WL, Liu YB, Hu JN, et al. Ginsenoside Rg2 alleviates HFD\/STZ-induced diabetic nephropathy by inhibiting pyroptosis via NF-\u03baB\/NLRP3 signaling pathways. Am J Chin Med. 2025;53:909\u201330.","journal-title":"Am J Chin Med"},{"key":"3778_CR37","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.jgr.2025.02.001","volume":"49","author":"J Zhang","year":"2025","unstructured":"Zhang J, Xie J, Niu Z, You L, Liu Y, Guo R, et al. Ginsenoside Rg2, a principal effective ingredient of Panax ginseng, attenuates DSS-induced ulcerative colitis through NF-\u03baB\/NLRP3 pathway. J Ginseng Res. 2025;49:282\u201393.","journal-title":"J Ginseng Res"},{"key":"3778_CR38","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1016\/j.jgr.2019.06.005","volume":"44","author":"D Gou","year":"2020","unstructured":"Gou D, Pei X, Wang J, Wang Y, Hu C, Song C, et al. Antiarrhythmic effects of ginsenoside Rg2 on calcium chloride-induced arrhythmias without oral toxicity. J Ginseng Res. 2020;44:717\u201324.","journal-title":"J Ginseng Res"},{"key":"3778_CR39","doi-asserted-by":"publisher","first-page":"23947","DOI":"10.1039\/C8RA02316F","volume":"8","author":"W Fu","year":"2018","unstructured":"Fu W, Xu H, Yu X, Lyu C, Tian Y, Guo M, et al. 20(S)-Ginsenoside Rg2 attenuates myocardial ischemia\/reperfusion injury by reducing oxidative stress and inflammation: role of SIRT1. RSC Adv. 2018;8:23947\u201362.","journal-title":"RSC Adv"},{"key":"3778_CR40","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.118.011699","volume":"8","author":"K Matsumura","year":"2019","unstructured":"Matsumura K, Kumar TP, Guddanti T, Yan Y, Blackburn SL, McBride DW. Neurobehavioral deficits after subarachnoid hemorrhage in mice: sensitivity analysis and development of a new composite score. J Am Heart Assoc. 2019;8:e011699.","journal-title":"J Am Heart Assoc"},{"key":"3778_CR41","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103026","volume":"69","author":"ZJ Yang","year":"2024","unstructured":"Yang ZJ, Huang SY, Zhong KY, Huang WG, Huang ZH, He TT, et al. Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m(6)A-YTHDF2-dependent manner. Redox Biol. 2024;69:103026.","journal-title":"Redox Biol"},{"key":"3778_CR42","doi-asserted-by":"publisher","first-page":"W720","DOI":"10.1093\/nar\/gkl167","volume":"34","author":"J Wu","year":"2006","unstructured":"Wu J, Mao X, Cai T, Luo J, Wei L. KOBAS server: a web-based platform for automated annotation and pathway identification. Nucleic Acids Res. 2006;34:W720-724.","journal-title":"Nucleic Acids Res"},{"key":"3778_CR43","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-025-00818-z","volume":"20","author":"RX Zhu","year":"2025","unstructured":"Zhu RX, Han RX, Chen YH, Huang L, Liu T, Jiang J, et al. Inactivation of NLRP3 inflammasome by dephosphorylation at Serine 658 alleviates glial inflammation in the mouse model of Parkinson\u2019s disease. Mol Neurodegener. 2025;20:27.","journal-title":"Mol Neurodegener"},{"key":"3778_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.114609","volume":"43","author":"J Xu","year":"2024","unstructured":"Xu J, Pickard JM, N\u00fa\u00f1ez G. FDA-approved disulfiram inhibits the NLRP3 inflammasome by regulating NLRP3 palmitoylation. Cell Rep. 2024;43:114609.","journal-title":"Cell Rep"},{"key":"3778_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101310","volume":"4","author":"X Jin","year":"2023","unstructured":"Jin X, Liu D, Zhou X, Luo X, Huang Q, Huang Y. Entrectinib inhibits NLRP3 inflammasome and inflammatory diseases by directly targeting NEK7. Cell Rep Med. 2023;4:101310.","journal-title":"Cell Rep Med"},{"key":"3778_CR46","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1161\/STROKEAHA.121.037769","volume":"53","author":"J Liu","year":"2022","unstructured":"Liu J, Li N, Zhu Z, Kiang KM-Y, Ng ACK, Dong CM, et al. Vitamin D enhances hematoma clearance and neurologic recovery in intracerebral hemorrhage. Stroke. 2022;53:2058\u201368.","journal-title":"Stroke"},{"key":"3778_CR47","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01853-x","volume":"17","author":"S Chen","year":"2020","unstructured":"Chen S, Peng J, Sherchan P, Ma Y, Xiang S, Yan F, et al. TREM2 activation attenuates neuroinflammation and neuronal apoptosis via PI3K\/Akt pathway after intracerebral hemorrhage in mice. J Neuroinflammation. 2020;17:168.","journal-title":"J Neuroinflammation"},{"key":"3778_CR48","doi-asserted-by":"publisher","first-page":"1314","DOI":"10.1126\/science.1110647","volume":"308","author":"A Nimmerjahn","year":"2005","unstructured":"Nimmerjahn A, Kirchhoff F, Helmchen F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science. 2005;308:1314\u20138.","journal-title":"Science"},{"key":"3778_CR49","doi-asserted-by":"publisher","first-page":"1488","DOI":"10.1038\/s12276-024-01261-8","volume":"56","author":"R Ramachandran","year":"2024","unstructured":"Ramachandran R, Manan A, Kim J, Choi S. NLRP3 inflammasome: a key player in the pathogenesis of life-style disorders. Exp Mol Med. 2024;56:1488\u2013500.","journal-title":"Exp Mol Med"},{"key":"3778_CR50","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1038\/s41577-019-0165-0","volume":"19","author":"KV Swanson","year":"2019","unstructured":"Swanson KV, Deng M, Ting JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19:477\u201389.","journal-title":"Nat Rev Immunol"},{"key":"3778_CR51","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117382","volume":"179","author":"Z Jin","year":"2024","unstructured":"Jin Z, Lu J, Xu H, Zhang Y, Zhang S, Zhang D, et al. Exploring the correlation between innate immune activation of inflammasome and regulation of pyroptosis after intracerebral hemorrhage: from mechanism to treatment. Biomed Pharmacother. 2024;179:117382.","journal-title":"Biomed Pharmacother"},{"key":"3778_CR52","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111442","volume":"138","author":"QL Chen","year":"2021","unstructured":"Chen QL, Yin HR, He QY, Wang Y. Targeting the NLRP3 inflammasome as new therapeutic avenue for inflammatory bowel disease. Biomed Pharmacother. 2021;138:111442.","journal-title":"Biomed Pharmacother"},{"key":"3778_CR53","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02641-5","volume":"19","author":"K Akeret","year":"2022","unstructured":"Akeret K, Buzzi RM, Thomson BR, Schwendinger N, Klohs J, Schulthess-Lutz N, et al. MyD88-TLR4-dependent choroid plexus activation precedes perilesional inflammation and secondary brain edema in a mouse model of intracerebral hemorrhage. J Neuroinflammation. 2022;19:290.","journal-title":"J Neuroinflammation"},{"key":"3778_CR54","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-46","volume":"9","author":"S Lin","year":"2012","unstructured":"Lin S, Yin Q, Zhong Q, Lv FL, Zhou Y, Li JQ, et al. Heme activates TLR4-mediated inflammatory injury via MyD88\/TRIF signaling pathway in intracerebral hemorrhage. J Neuroinflammation. 2012;9:46.","journal-title":"J Neuroinflammation"},{"key":"3778_CR55","doi-asserted-by":"publisher","first-page":"745","DOI":"10.2147\/IJGM.S507518","volume":"18","author":"Y Cai","year":"2025","unstructured":"Cai Y, Ma Y, Tang C, Li W, Lv X, Xie Z, et al. Prognostic significance of serum NLRP3 in spontaneous intracerebral hemorrhage. Int J Gen Med. 2025;18:745\u201357.","journal-title":"Int J Gen Med"},{"key":"3778_CR56","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1007\/s12975-022-01064-x","volume":"14","author":"E D\u00edaz-Garc\u00eda","year":"2023","unstructured":"D\u00edaz-Garc\u00eda E, Nanwani-Nanwani K, Garc\u00eda-Tovar S, Alfaro E, L\u00f3pez-Collazo E, Quintana-D\u00edaz M, et al. NLRP3 inflammasome overactivation in patients with aneurysmal subarachnoid hemorrhage. Transl Stroke Res. 2023;14:334\u201346.","journal-title":"Transl Stroke Res"},{"key":"3778_CR57","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1007\/s12975-014-0384-4","volume":"6","author":"S Chen","year":"2015","unstructured":"Chen S, Yang Q, Chen G, Zhang JH. An update on inflammation in the acute phase of intracerebral hemorrhage. Transl Stroke Res. 2015;6:4\u20138.","journal-title":"Transl Stroke Res"},{"key":"3778_CR58","doi-asserted-by":"publisher","first-page":"3431","DOI":"10.1007\/s43032-021-00692-2","volume":"28","author":"L Cai","year":"2021","unstructured":"Cai L, Hu F, Fu W, Yu X, Zhong W, Liu F, et al. Ginsenoside Rg2 ameliorates brain injury after intracerebral hemorrhage in a rat model of preeclampsia. Reprod Sci. 2021;28:3431\u20139.","journal-title":"Reprod Sci"},{"key":"3778_CR59","doi-asserted-by":"publisher","first-page":"14640","DOI":"10.1021\/acs.jafc.4c00181","volume":"72","author":"P Yin","year":"2024","unstructured":"Yin P, Wang H, Xue T, Yu X, Meng X, Mi Q, et al. Four-dimensional label-free quantitative proteomics of ginsenoside Rg(2) ameliorated scopolamine-induced memory impairment in mice through the lysosomal pathway. J Agric Food Chem. 2024;72:14640\u201352.","journal-title":"J Agric Food Chem"},{"key":"3778_CR60","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.330589","author":"J Chen","year":"2022","unstructured":"Chen J, Zheng ZV, Lu G, Chan WY, Zhang Y, Wong GKC. Microglia activation, classification and microglia-mediated neuroinflammatory modulators in subarachnoid hemorrhage. Neural Regen Res. 2022.","journal-title":"Neural Regen Res"},{"key":"3778_CR61","doi-asserted-by":"publisher","first-page":"32679","DOI":"10.1073\/pnas.2018497117","volume":"117","author":"J Xu","year":"2020","unstructured":"Xu J, Chen Z, Yu F, Liu H, Ma C, Xie D, et al. IL-4\/STAT6 signaling facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice. Proc Natl Acad Sci U S A. 2020;117:32679\u201390.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3778_CR62","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03105-8","volume":"21","author":"X Deng","year":"2024","unstructured":"Deng X, Ren J, Chen K, Zhang J, Zhang Q, Zeng J, et al. Mas receptor activation facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice. J Neuroinflammation. 2024;21:106.","journal-title":"J Neuroinflammation"},{"key":"3778_CR63","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1161\/STROKEAHA.116.015609","volume":"48","author":"M Zille","year":"2017","unstructured":"Zille M, Karuppagounder SS, Chen Y, Gough PJ, Bertin J, Finger J, Milner TA, Jonas EA, Ratan RR. Neuronal death after hemorrhagic stroke in vitro and in vivo shares features of ferroptosis and necroptosis. Stroke. 2017;48:1033\u201343.","journal-title":"Stroke"},{"key":"3778_CR64","doi-asserted-by":"publisher","DOI":"10.31083\/j.jin2206168","volume":"22","author":"XY Xiong","year":"2023","unstructured":"Xiong XY, Liang YJ, Zhang XX, Yang SH, Zhong ZQ, Liu SQ, et al. PKM2 Nuclear Translocation Promotes Glial Cell Activation and Aggravates the Brain Injury of Intracerebral Hemorrhage. J Integr Neurosci. 2023;22:168.","journal-title":"J Integr Neurosci"},{"key":"3778_CR65","doi-asserted-by":"publisher","DOI":"10.3390\/nu13030856","author":"F Wang","year":"2021","unstructured":"Wang F, Park JS, Ma Y, Ma H, Lee YJ, Lee GR, et al. Ginseng saponin enriched in Rh1 and Rg2 ameliorates nonalcoholic fatty liver disease by inhibiting inflammasome activation. Nutrients. 2021.","journal-title":"Nutrients"},{"key":"3778_CR66","doi-asserted-by":"publisher","first-page":"4021","DOI":"10.1161\/STROKEAHA.120.033285","volume":"52","author":"J Yan","year":"2021","unstructured":"Yan J, Xu W, Lenahan C, Huang L, Wen J, Li G, et al. CCR5 Activation Promotes NLRP1-Dependent Neuronal Pyroptosis via CCR5\/PKA\/CREB Pathway After Intracerebral Hemorrhage. Stroke. 2021;52:4021\u201332.","journal-title":"Stroke"},{"key":"3778_CR67","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.1177\/0271678X16666551","volume":"37","author":"M Li","year":"2017","unstructured":"Li M, Li Z, Ren H, Jin WN, Wood K, Liu Q, et al. Colony stimulating factor 1 receptor inhibition eliminates microglia and attenuates brain injury after intracerebral hemorrhage. J Cereb Blood Flow Metab. 2017;37:2383\u201395.","journal-title":"J Cereb Blood Flow Metab"},{"key":"3778_CR68","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.51796","author":"L Zhan","year":"2020","unstructured":"Zhan L, Fan L, Kodama L, Sohn PD, Wong MY, Mousa GA, et al. A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain. Elife. 2020.","journal-title":"Elife"},{"key":"3778_CR69","doi-asserted-by":"publisher","first-page":"3238","DOI":"10.1016\/j.cell.2025.03.041","volume":"188","author":"AC Geraghty","year":"2025","unstructured":"Geraghty AC, Acosta-Alvarez L, Rotiroti MC, Dutton S, O\u2019Dea MR, Kim W, et al. Immunotherapy-related cognitive impairment after CAR T cell therapy in mice. Cell. 2025;188:3238-3258.e3225.","journal-title":"Cell"},{"key":"3778_CR70","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1186\/s13023-023-02926-9","volume":"18","author":"C McCabe","year":"2023","unstructured":"McCabe C, Wright H, Polson K, Wagner AJ. Supporting patients in the transition to the revised pexidartinib dosing regimen: perspectives from the multidisciplinary clinical and allied health professional team. Orphanet J Rare Dis. 2023;18:313.","journal-title":"Orphanet J Rare Dis"},{"key":"3778_CR71","doi-asserted-by":"publisher","first-page":"23336","DOI":"10.1073\/pnas.1922788117","volume":"117","author":"F Lei","year":"2020","unstructured":"Lei F, Cui N, Zhou C, Chodosh J, Vavvas DG, Paschalis EI. CSF1R inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages. Proc Natl Acad Sci U S A. 2020;117:23336\u20138.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3778_CR72","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1283711","volume":"14","author":"W Claeys","year":"2023","unstructured":"Claeys W, Verhaege D, Van Imschoot G, Van Wonterghem E, Van Acker L, Amelinck L, et al. Limitations of PLX3397 as a microglial investigational tool: peripheral and off-target effects dictate the response to inflammation. Front Immunol. 2023;14:1283711.","journal-title":"Front Immunol"},{"key":"3778_CR73","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1161\/STROKEAHA.117.018904","volume":"49","author":"H Ren","year":"2018","unstructured":"Ren H, Kong Y, Liu Z, Zang D, Yang X, Wood K, et al. Selective NLRP3 (Pyrin Domain-Containing Protein 3) Inflammasome Inhibitor Reduces Brain Injury After Intracerebral Hemorrhage. Stroke. 2018;49:184\u201392.","journal-title":"Stroke"},{"key":"3778_CR74","doi-asserted-by":"publisher","first-page":"4215","DOI":"10.1021\/acs.jafc.0c00833","volume":"68","author":"B Cheng","year":"2020","unstructured":"Cheng B, Gao W, Wu X, Zheng M, Yu Y, Song C, et al. Ginsenoside Rg2 Ameliorates High-Fat Diet-Induced Metabolic Disease through SIRT1. J Agric Food Chem. 2020;68:4215\u201326.","journal-title":"J Agric Food Chem"},{"key":"3778_CR75","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.brainresbull.2017.08.009","volume":"134","author":"Y Ren","year":"2017","unstructured":"Ren Y, Wang JL, Zhang X, Wang H, Ye Y, Song L, et al. Antidepressant-like effects of ginsenoside Rg2 in a chronic mild stress model of depression. Brain Res Bull. 2017;134:211\u20139.","journal-title":"Brain Res Bull"},{"key":"3778_CR76","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.jep.2006.12.015","volume":"111","author":"N Li","year":"2007","unstructured":"Li N, Liu B, Dluzen DE, Jin Y. Protective effects of ginsenoside Rg2 against glutamate-induced neurotoxicity in PC12 cells. J Ethnopharmacol. 2007;111:458\u201363.","journal-title":"J Ethnopharmacol"},{"key":"3778_CR77","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1038\/s41423-021-00740-6","volume":"18","author":"Y Huang","year":"2021","unstructured":"Huang Y, Xu W, Zhou R. NLRP3 inflammasome activation and cell death. Cell Mol Immunol. 2021;18:2114\u201327.","journal-title":"Cell Mol Immunol"},{"key":"3778_CR78","doi-asserted-by":"publisher","first-page":"E4110","DOI":"10.1073\/pnas.1405023111","volume":"111","author":"FF Dutra","year":"2014","unstructured":"Dutra FF, Alves LS, Rodrigues D, Fernandez PL, de Oliveira RB, Golenbock DT, et al. Hemolysis-induced lethality involves inflammasome activation by heme. Proc Natl Acad Sci U S A. 2014;111:E4110-4118.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"3778_CR79","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186656","author":"DTN Huynh","year":"2020","unstructured":"Huynh DTN, Baek N, Sim S, Myung CS, Heo KS. Minor Ginsenoside Rg2 and Rh1 attenuates LPS-induced acute liver and kidney damages via downregulating activation of TLR4-STAT1 and inflammatory cytokine production in macrophages. Int J Mol Sci. 2020.","journal-title":"Int J Mol Sci"},{"key":"3778_CR80","doi-asserted-by":"publisher","DOI":"10.31083\/j.jin2206171","volume":"22","author":"B Wang","year":"2023","unstructured":"Wang B, Chen J, Wang S, Chen L, Zhang X, Zhou T, et al. Kv1.3 blockade alleviates white matter injury through reshaping M1\/M2 phenotypes via the NF-\u03baB signaling pathway after intracerebral hemorrhage. J Integr Neurosci. 2023;22:171.","journal-title":"J Integr Neurosci"},{"key":"3778_CR81","first-page":"2883","volume":"13","author":"Q Li","year":"2021","unstructured":"Li Q, Zhao Z, Si K, Zhou J, Du L, Liu H, et al. Correlation between the levels of NLRP3, Hcy, IL-1\u03b2, IL-18 and the prognosis in patients with hemorrhagic stroke. Am J Transl Res. 2021;13:2883\u201390.","journal-title":"Am J Transl Res"},{"key":"3778_CR82","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1002\/ana.24070","volume":"75","author":"Q Ma","year":"2014","unstructured":"Ma Q, Chen S, Hu Q, Feng H, Zhang JH, Tang J. NLRP3 inflammasome contributes to inflammation after intracerebral hemorrhage. Ann Neurol. 2014;75:209\u201319.","journal-title":"Ann Neurol"},{"key":"3778_CR83","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1526786","volume":"16","author":"KL He","year":"2025","unstructured":"He KL, Yu X, Xia L, Xie YD, Qi EB, Wan L, et al. A new perspective on the regulation of neuroinflammation in intracerebral hemorrhage: mechanisms of NLRP3 inflammasome activation and therapeutic strategies. Front Immunol. 2025;16:1526786.","journal-title":"Front Immunol"},{"key":"3778_CR84","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/s41582-024-01035-w","volume":"20","author":"DJ Seiffge","year":"2024","unstructured":"Seiffge DJ, Fandler-H\u00f6fler S, Du Y, Goeldlin MB, Jolink WMT, Klijn CJM, et al. Intracerebral haemorrhage - mechanisms, diagnosis and prospects for treatment and prevention. Nat Rev Neurol. 2024;20:708\u201323.","journal-title":"Nat Rev Neurol"},{"key":"3778_CR85","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1007\/s12975-017-0559-x","volume":"9","author":"Z Wang","year":"2018","unstructured":"Wang Z, Zhou F, Dou Y, Tian X, Liu C, Li H, et al. Melatonin alleviates intracerebral hemorrhage-induced secondary brain injury in rats via suppressing apoptosis, inflammation, oxidative stress, DNA damage, and mitochondria injury. Transl Stroke Res. 2018;9:74\u201391.","journal-title":"Transl Stroke Res"},{"key":"3778_CR86","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1177\/0271678X17753590","volume":"38","author":"DA Wilkinson","year":"2018","unstructured":"Wilkinson DA, Keep RF, Hua Y, Xi G. Hematoma clearance as a therapeutic target in intracerebral hemorrhage: from macro to micro. J Cereb Blood Flow Metab. 2018;38:741\u20135.","journal-title":"J Cereb Blood Flow Metab"},{"key":"3778_CR87","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1007\/s12975-021-00889-2","volume":"12","author":"X Fu","year":"2021","unstructured":"Fu X, Zeng H, Zhao J, Zhou G, Zhou H, Zhuang J, et al. Inhibition of Dectin-1 ameliorates neuroinflammation by regulating microglia\/macrophage phenotype after intracerebral hemorrhage in mice. Transl Stroke Res. 2021;12:1018\u201334.","journal-title":"Transl Stroke Res"}],"container-title":["Journal of Neuroinflammation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12974-026-03778-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-026-03778-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12974-026-03778-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T19:03:08Z","timestamp":1778007788000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12974-026-03778-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,26]]},"references-count":87,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3778"],"URL":"https:\/\/doi.org\/10.1186\/s12974-026-03778-3","relation":{},"ISSN":["1742-2094"],"issn-type":[{"value":"1742-2094","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,26]]},"assertion":[{"value":"6 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All experimental procedures involving animals were conducted in accordance with the guidelines of the Laboratory Animal Ethics Committee of the School of Pharmaceutical Sciences, Jilin University (Approval No. 20240090). This study was approved by the Ethics Committee of the Second Hospital of Jilin University (Approval No. 2025\u2013188), and informed consent was obtained from all participants or their legal guardians.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"150"}}