{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:51:31Z","timestamp":1786632691643,"version":"build-2736575974"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"National Science and Technology Major Project for Noncommunicable Chronic Diseases","award":["2023ZD0505000"],"award-info":[{"award-number":["2023ZD0505000"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82403930"],"award-info":[{"award-number":["82403930"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401724"],"award-info":[{"award-number":["82401724"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371299"],"award-info":[{"award-number":["82371299"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82501751"],"award-info":[{"award-number":["82501751"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LMS26H090001"],"award-info":[{"award-number":["LMS26H090001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Education Project, Zhejiang Province, China","award":["Y202045451"],"award-info":[{"award-number":["Y202045451"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Transl Med"],"DOI":"10.1186\/s12967-026-08523-1","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T11:00:03Z","timestamp":1782817203000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["CTSS regulates macrophage lipid metabolic reprogramming and white matter repair after intracerebral hemorrhage"],"prefix":"10.1186","volume":"24","author":[{"given":"Xian","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahe","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yirui","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaijun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linfeng","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghe","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shandong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0437-0239","authenticated-orcid":false,"given":"Chi","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"issue":"2","key":"8523_CR1","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/S1474-4422(09)70340-0","volume":"9","author":"CJ van Asch","year":"2010","unstructured":"van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: a systematic review and meta-analysis. Lancet Neurol. 2010;9(2):167\u201376.","journal-title":"Lancet Neurol"},{"issue":"6","key":"8523_CR2","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1136\/jnnp-2013-306476","volume":"85","author":"MT Poon","year":"2014","unstructured":"Poon MT, Fonville AF, Al-Shahi Salman R. Long-term prognosis after intracerebral haemorrhage: systematic review and meta-analysis. J Neurol Neurosurg Psychiatry. 2014;85(6):660\u20137.","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"5","key":"8523_CR3","doi-asserted-by":"publisher","first-page":"e259","DOI":"10.1016\/S2214-109X(13)70089-5","volume":"1","author":"RV Krishnamurthi","year":"2013","unstructured":"Krishnamurthi RV, Feigin VL, Forouzanfar MH, Mensah GA, Connor M, Bennett DA, et al. Global and regional burden of first-ever ischaemic and haemorrhagic stroke during 1990\u20132010: findings from the Global Burden of Disease Study 2010. Lancet Glob Health. 2013;1(5):e259\u201381.","journal-title":"Lancet Glob Health"},{"issue":"5","key":"8523_CR4","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1161\/STROKEAHA.123.044622","volume":"55","author":"JR Senff","year":"2024","unstructured":"Senff JR, Singh SD, Pasi M, Jolink WMT, Rodrigues MA, Schreuder F, et al. Long-Term Outcomes in Patients With Spontaneous Cerebellar Hemorrhage: An International Cohort Study. Stroke. 2024;55(5):1210\u20137.","journal-title":"Stroke"},{"issue":"8","key":"8523_CR5","doi-asserted-by":"publisher","first-page":"820","DOI":"10.1016\/S1474-4422(16)00130-7","volume":"15","author":"S Moulin","year":"2016","unstructured":"Moulin S, Labreuche J, Bombois S, Rossi C, Boulouis G, H\u00e9non H, et al. Dementia risk after spontaneous intracerebral haemorrhage: a prospective cohort study. Lancet Neurol. 2016;15(8):820\u20139.","journal-title":"Lancet Neurol"},{"key":"8523_CR6","doi-asserted-by":"crossref","unstructured":"Correction to Lancet Neurol. 2021;20:437\u201347. Lancet Neurol. 2021;20(8):e5.","DOI":"10.1016\/S1474-4422(21)00185-X"},{"key":"8523_CR7","doi-asserted-by":"crossref","unstructured":"Novakovic N, Linzey JR, Chenevert TL, Gemmete JJ, Troost JP, Xi G, et al. White matter survival within and around the hematoma: quantification by MRI in patients with intracerebral hemorrhage. Biomolecules. 2021;11(6).","DOI":"10.3390\/biom11060910"},{"issue":"3","key":"8523_CR8","doi-asserted-by":"publisher","first-page":"669","DOI":"10.2174\/1570159X20666220830115018","volume":"21","author":"L Xiao","year":"2023","unstructured":"Xiao L, Wang M, Shi Y, Xu Y, Gao Y, Zhang W, et al. Secondary White Matter Injury Mediated by Neuroinflammation after Intracerebral Hemorrhage and Promising Therapeutic Strategies of Targeting the NLRP3 Inflammasome. Curr Neuropharmacol. 2023;21(3):669\u201386.","journal-title":"Curr Neuropharmacol"},{"issue":"1","key":"8523_CR9","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1186\/s12974-025-03483-7","volume":"22","author":"H Huang","year":"2025","unstructured":"Huang H, Kuang Y, Chen Y, Zhang Y, Zhou J, Yu X, et al. Pro-repair macrophages driven by CGRP rescue white matter integrity following intracerebral hemorrhage. J Neuroinflammation. 2025;22(1):161.","journal-title":"J Neuroinflammation"},{"issue":"1","key":"8523_CR10","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1186\/s12974-022-02561-4","volume":"19","author":"M Yao","year":"2022","unstructured":"Yao M, Fang J, Li J, Ng ACK, Liu J, Leung GKK, et al. Modulation of the proteoglycan receptor PTP\u03c3 promotes white matter integrity and functional recovery after intracerebral hemorrhage stroke in mice. J Neuroinflammation. 2022;19(1):207.","journal-title":"J Neuroinflammation"},{"issue":"9","key":"8523_CR11","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1038\/s41577-019-0167-y","volume":"19","author":"G Lemke","year":"2019","unstructured":"Lemke G. How macrophages deal with death. Nat Rev Immunol. 2019;19(9):539\u201349.","journal-title":"Nat Rev Immunol"},{"issue":"1","key":"8523_CR12","doi-asserted-by":"publisher","first-page":"e70041","DOI":"10.1002\/jev2.70041","volume":"14","author":"L Hu","year":"2025","unstructured":"Hu L, Chen Z, Lu J, Jiang S, Lin H, Zhou J, et al. Extracellular Vesicles From Bone Marrow-Derived Macrophages Enriched in ARG1 Enhance Microglial Phagocytosis and Haematoma Clearance Following Intracerebral Haemorrhage. J Extracell Vesicles. 2025;14(1):e70041.","journal-title":"J Extracell Vesicles"},{"issue":"1","key":"8523_CR13","doi-asserted-by":"publisher","first-page":"283","DOI":"10.7150\/thno.90370","volume":"14","author":"L Fan","year":"2024","unstructured":"Fan L, Jin L, Tang T, Zheng Y, Chen Z, Lin H, et al. Neutrophil-like pH-responsive pro-efferocytic nanoparticles improve neurological recovery by promoting erythrophagocytosis after intracerebral hemorrhage. Theranostics. 2024;14(1):283\u2013303.","journal-title":"Theranostics"},{"issue":"1","key":"8523_CR14","doi-asserted-by":"publisher","first-page":"8077","DOI":"10.1038\/s41467-025-62053-w","volume":"16","author":"M Loix","year":"2025","unstructured":"Loix M, Vanherle S, Bolkaerts L, Verberk SGS, Punt M, Wouters F, et al. UBE3A promotes foam cell formation and counters remyelination by targeting ABCA1 for proteasomal degradation. Nat Commun. 2025;16(1):8077.","journal-title":"Nat Commun"},{"key":"8523_CR15","doi-asserted-by":"publisher","first-page":"103857","DOI":"10.1016\/j.redox.2025.103857","volume":"86","author":"M Xia","year":"2025","unstructured":"Xia M, Li C, Zhang Y, Wang T, Zhang C, Zhou J, et al. GLP-1R activation restores Gas6-driven efferocytosis in senescent foamy macrophages to promote neural repair. Redox Biol. 2025;86:103857.","journal-title":"Redox Biol"},{"key":"8523_CR16","doi-asserted-by":"publisher","first-page":"101106","DOI":"10.1016\/j.mam.2022.101106","volume":"88","author":"P Smyth","year":"2022","unstructured":"Smyth P, Sasiwachirangkul J, Williams R, Scott CJ. Cathepsin S (CTSS) activity in health and disease - A treasure trove of untapped clinical potential. Mol Aspects Med. 2022;88:101106.","journal-title":"Mol Aspects Med"},{"issue":"3","key":"8523_CR17","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1053\/j.gastro.2023.05.039","volume":"165","author":"T Zuo","year":"2023","unstructured":"Zuo T, Xie Q, Liu J, Yang J, Shi J, Kong D, et al. Macrophage-Derived Cathepsin S Remodels the Extracellular Matrix to Promote Liver Fibrogenesis. Gastroenterology. 2023;165(3):746\u2013e6116.","journal-title":"Gastroenterology"},{"key":"8523_CR18","doi-asserted-by":"publisher","first-page":"1531125","DOI":"10.3389\/fcimb.2025.1531125","volume":"15","author":"XT Luo","year":"2025","unstructured":"Luo XT, Hu HR, Sun ZD, Zhang LH, Li Y. Multi-omics analysis reveals that low cathepsin S expression aggravates sepsis progression and worse prognosis via inducing monocyte polarization. Front Cell Infect Microbiol. 2025;15:1531125.","journal-title":"Front Cell Infect Microbiol"},{"issue":"1","key":"8523_CR19","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1186\/s12974-023-02943-2","volume":"20","author":"E Oshima","year":"2023","unstructured":"Oshima E, Hayashi Y, Xie Z, Sato H, Hitomi S, Shibuta I, et al. M2 macrophage-derived cathepsin S promotes peripheral nerve regeneration via fibroblast-Schwann cell-signaling relay. J Neuroinflammation. 2023;20(1):258.","journal-title":"J Neuroinflammation"},{"issue":"1","key":"8523_CR20","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1007\/s12035-026-05732-z","volume":"63","author":"S Xu","year":"2026","unstructured":"Xu S, Liang J, Wang J, Li J, Wang S, Wang X, et al. Macrophage-Derived Amphiregulin Enhances Schwann Cell Phagocytosis Through the EGFR\/CTSS Signaling Pathway. Mol Neurobiol. 2026;63(1):457.","journal-title":"Mol Neurobiol"},{"issue":"1","key":"8523_CR21","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s12903-018-0518-2","volume":"18","author":"S Memmert","year":"2018","unstructured":"Memmert S, Nokhbehsaim M, Damanaki A, Nogueira AVB, Papadopoulou AK, Piperi C, et al. Role of cathepsin S In periodontal wound healing-an in vitro study on human PDL cells. BMC Oral Health. 2018;18(1):60.","journal-title":"BMC Oral Health"},{"key":"8523_CR22","doi-asserted-by":"crossref","unstructured":"Pandey SP, Yang D, Hedden L, Laughlin CR, Wang W, Soto AS, et al. Gasdermin C cleavage by Cathepsin S modulates Rab7 vesicles in intestinal epithelial cells to amplify anti-helminth immunity. Immunity. 2025;58(10):2439-2455.e8.","DOI":"10.1016\/j.immuni.2025.06.018"},{"key":"8523_CR23","doi-asserted-by":"publisher","first-page":"103815","DOI":"10.1016\/j.redox.2025.103815","volume":"86","author":"RC Xu","year":"2025","unstructured":"Xu RC, Sun JL, Wang F, Liu HH, Qi ZR, Shi X, et al. Cathepsin S regulates ferroptosis sensitivity in hepatocellular carcinoma through the KEAP1-NRF2 signaling pathway. Redox Biol. 2025;86:103815.","journal-title":"Redox Biol"},{"issue":"1","key":"8523_CR24","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1172\/JCI88647","volume":"127","author":"RA Taylor","year":"2017","unstructured":"Taylor RA, Chang CF, Goods BA, Hammond MD, Mac Grory B, Ai Y, et al. TGF-\u03b21 modulates microglial phenotype and promotes recovery after intracerebral hemorrhage. J Clin Invest. 2017;127(1):280\u201392.","journal-title":"J Clin Invest"},{"issue":"1","key":"8523_CR25","doi-asserted-by":"publisher","first-page":"2739","DOI":"10.1038\/s41598-025-32489-7","volume":"16","author":"BM Anderson","year":"2025","unstructured":"Anderson BM, Ziegler AR, Campden RI, Wu H, Xu B, McQuade RM, et al. Probing the activity of cysteine cathepsins in inflammatory bowel diseases. Sci Rep. 2025;16(1):2739.","journal-title":"Sci Rep"},{"issue":"1","key":"8523_CR26","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s13041-023-01051-9","volume":"16","author":"HJ Lee","year":"2023","unstructured":"Lee HJ, Hwang JW, Park JH, Jeong YJ, Jang JY, Hoe HS. Profiling tyrosine kinase inhibitors as AD therapeutics in a mouse model of AD. Mol Brain. 2023;16(1):63.","journal-title":"Mol Brain"},{"key":"8523_CR27","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.bbi.2022.11.001","volume":"107","author":"L Xie","year":"2023","unstructured":"Xie L, Zhang S, Huang L, Peng Z, Lu H, He Q, et al. Single-cell RNA sequencing of peripheral blood reveals that monocytes with high cathepsin S expression aggravate cerebral ischemia-reperfusion injury. Brain Behav Immun. 2023;107:330\u201344.","journal-title":"Brain Behav Immun"},{"key":"8523_CR28","doi-asserted-by":"publisher","first-page":"118744","DOI":"10.1016\/j.biopha.2025.118744","volume":"193","author":"C Fr\u00f8rup","year":"2025","unstructured":"Fr\u00f8rup C, Svane CAB, H\u00f8j Jensen M, Holm LJ, Pedersen K, M\u00f8nsted M, et al. Evaluation of the pharmacological cathepsin S inhibitor LY3000328 on autoimmune diabetes in mice. Biomed Pharmacother. 2025;193:118744.","journal-title":"Biomed Pharmacother"},{"issue":"6","key":"8523_CR29","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1136\/svn-2023-002331","volume":"8","author":"R Zhang","year":"2023","unstructured":"Zhang R, Dong Y, Liu Y, Moezzi D, Ghorbani S, Mirzaei R, et al. Enhanced liver X receptor signalling reduces brain injury and promotes tissue regeneration following experimental intracerebral haemorrhage: roles of microglia\/macrophages. Stroke Vasc Neurol. 2023;8(6):486\u2013502.","journal-title":"Stroke Vasc Neurol"},{"issue":"1","key":"8523_CR30","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1038\/nprot.2014.011","volume":"9","author":"H Peng","year":"2014","unstructured":"Peng H, Bria A, Zhou Z, Iannello G, Long F. Extensible visualization and analysis for multidimensional images using Vaa3D. Nat Protoc. 2014;9(1):193\u2013208.","journal-title":"Nat Protoc"},{"issue":"1","key":"8523_CR31","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/cdd.2016.109","volume":"24","author":"C Rodr\u00edguez","year":"2017","unstructured":"Rodr\u00edguez C, Sobrino T, Agulla J, Bobo-Jim\u00e9nez V, Ramos-Araque ME, Duarte JJ, et al. Neovascularization and functional recovery after intracerebral hemorrhage is conditioned by the Tp53 Arg72Pro single-nucleotide polymorphism. Cell Death Differ. 2017;24(1):144\u201354.","journal-title":"Cell Death Differ"},{"issue":"10","key":"8523_CR32","doi-asserted-by":"publisher","first-page":"1560","DOI":"10.1038\/nprot.2009.125","volume":"4","author":"V Bouet","year":"2009","unstructured":"Bouet V, Boulouard M, Toutain J, Divoux D, Bernaudin M, Schumann-Bard P, et al. The adhesive removal test: a sensitive method to assess sensorimotor deficits in mice. Nat Protoc. 2009;4(10):1560\u20134.","journal-title":"Nat Protoc"},{"issue":"6","key":"8523_CR33","doi-asserted-by":"publisher","first-page":"e3000330","DOI":"10.1371\/journal.pbio.3000330","volume":"17","author":"Q Zhang","year":"2019","unstructured":"Zhang Q, Zhu W, Xu F, Dai X, Shi L, Cai W, et al. The interleukin-4\/PPAR\u03b3 signaling axis promotes oligodendrocyte differentiation and remyelination after brain injury. PLoS Biol. 2019;17(6):e3000330.","journal-title":"PLoS Biol"},{"issue":"14","key":"8523_CR34","doi-asserted-by":"publisher","first-page":"6628","DOI":"10.7150\/thno.113764","volume":"15","author":"Y Zheng","year":"2025","unstructured":"Zheng Y, Li Y, He X, Zhu Y, Xu S, Feng Y, et al. Gut microbiota depletion accelerates hematoma resolution and neurological recovery after intracerebral hemorrhage via p-coumaric acid-promoted Treg differentiation. Theranostics. 2025;15(14):6628\u201350.","journal-title":"Theranostics"},{"issue":"1","key":"8523_CR35","doi-asserted-by":"publisher","first-page":"3089","DOI":"10.1038\/s41467-025-58254-y","volume":"16","author":"X Zhang","year":"2025","unstructured":"Zhang X, Li H, Gu Y, Ping A, Chen J, Zhang Q, et al. Repair-associated macrophages increase after early-phase microglia attenuation to promote ischemic stroke recovery. Nat Commun. 2025;16(1):3089.","journal-title":"Nat Commun"},{"issue":"15","key":"8523_CR36","doi-asserted-by":"publisher","first-page":"5418","DOI":"10.7150\/thno.86103","volume":"13","author":"S Luo","year":"2023","unstructured":"Luo S, Zhao X, Jiang J, Deng B, Liu S, Xu H, et al. Piezo1 specific deletion in macrophage protects the progression of liver fibrosis in mice. Theranostics. 2023;13(15):5418\u201334.","journal-title":"Theranostics"},{"key":"8523_CR37","doi-asserted-by":"publisher","first-page":"106089","DOI":"10.1016\/j.bbi.2025.106089","volume":"130","author":"H Zang","year":"2025","unstructured":"Zang H, Hu Y, Ji X, Chen Y, He X, Wan L, et al. LXR-\u03b2 regulates microglial efferocytosis and neuroinflammation in CPSP via STAT6 activation. Brain Behav Immun. 2025;130:106089.","journal-title":"Brain Behav Immun"},{"issue":"1","key":"8523_CR38","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.jneumeth.2012.06.017","volume":"209","author":"TA Dincman","year":"2012","unstructured":"Dincman TA, Beare JE, Ohri SS, Whittemore SR. Isolation of cortical mouse oligodendrocyte precursor cells. J Neurosci Methods. 2012;209(1):219\u201326.","journal-title":"J Neurosci Methods"},{"issue":"7","key":"8523_CR39","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1016\/j.immuni.2021.04.022","volume":"54","author":"L Shi","year":"2021","unstructured":"Shi L, Sun Z, Su W, Xu F, Xie D, Zhang Q, et al. Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke. Immunity. 2021;54(7):1527\u2013e428.","journal-title":"Immunity"},{"key":"8523_CR40","doi-asserted-by":"publisher","first-page":"2510847","DOI":"10.1155\/2021\/2510847","volume":"2021","author":"Y Shen","year":"2021","unstructured":"Shen Y, Yang W, Xiong X, Li X, Xiao Z, Yu J, et al. Integrated Multiomics Analysis Identifies a Novel Biomarker Associated with Prognosis in Intracerebral Hemorrhage. Oxid Med Cell Longev. 2021;2021:2510847.","journal-title":"Oxid Med Cell Longev"},{"issue":"1","key":"8523_CR41","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s12974-025-03460-0","volume":"22","author":"B Zhu","year":"2025","unstructured":"Zhu B, Liu C, Luo M, Chen J, Tian S, Zhan T, et al. Spatiotemporal dynamic changes of meningeal microenvironment influence meningeal lymphatic function following subarachnoid hemorrhage: from inflammatory response to tissue remodeling. J Neuroinflammation. 2025;22(1):131.","journal-title":"J Neuroinflammation"},{"issue":"8077","key":"8523_CR42","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1038\/s41586-025-09233-2","volume":"644","author":"AMA Miranda","year":"2025","unstructured":"Miranda AMA, McAllan L, Mazzei G, Andrew I, Davies I, Ertugrul M, et al. Selective remodelling of the adipose niche in obesity and weight loss. Nature. 2025;644(8077):769\u201379.","journal-title":"Nature"},{"issue":"1","key":"8523_CR43","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1186\/s12967-025-06346-0","volume":"23","author":"J Chen","year":"2025","unstructured":"Chen J, Cui N, He SH, Xia CY, Li WQ. Single-cell transcriptomics reveals metabolic remodeling and functional specialization in the immune microenvironment of bone tumors. J Transl Med. 2025;23(1):554.","journal-title":"J Transl Med"},{"issue":"1","key":"8523_CR44","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1186\/s12974-022-02629-1","volume":"19","author":"M Hwang","year":"2022","unstructured":"Hwang M, Savarin C, Kim J, Powers J, Towne N, Oh H, et al. Trem2 deficiency impairs recovery and phagocytosis and dysregulates myeloid gene expression during virus-induced demyelination. J Neuroinflammation. 2022;19(1):267.","journal-title":"J Neuroinflammation"},{"issue":"1","key":"8523_CR45","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1186\/s12974-016-0524-8","volume":"13","author":"CH Wu","year":"2016","unstructured":"Wu CH, Chen CC, Lai CY, Hung TH, Lin CC, Chao M, et al. Treatment with TO901317, a synthetic liver X receptor agonist, reduces brain damage and attenuates neuroinflammation in experimental intracerebral hemorrhage. J Neuroinflammation. 2016;13(1):62.","journal-title":"J Neuroinflammation"},{"issue":"1","key":"8523_CR46","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1186\/s12931-020-01381-5","volume":"21","author":"R Brown","year":"2020","unstructured":"Brown R, Nath S, Lora A, Samaha G, Elgamal Z, Kaiser R, et al. Cathepsin S: investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics. Respir Res. 2020;21(1):111.","journal-title":"Respir Res"},{"issue":"1","key":"8523_CR47","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1007\/s00018-024-05274-4","volume":"81","author":"L Gallwitz","year":"2024","unstructured":"Gallwitz L, Bleibaum F, Voss M, Schweizer M, Spengler K, Winter D, et al. Cellular depletion of major cathepsin proteases reveals their concerted activities for lysosomal proteolysis. Cell Mol Life Sci. 2024;81(1):227.","journal-title":"Cell Mol Life Sci"},{"key":"8523_CR48","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s12989-016-0129-5","volume":"13","author":"CS Hughes","year":"2016","unstructured":"Hughes CS, Colhoun LM, Bains BK, Kilgour JD, Burden RE, Burrows JF, et al. Extracellular cathepsin S and intracellular caspase 1 activation are surrogate biomarkers of particulate-induced lysosomal disruption in macrophages. Part Fibre Toxicol. 2016;13:19.","journal-title":"Part Fibre Toxicol"},{"issue":"52","key":"8523_CR49","doi-asserted-by":"publisher","first-page":"14470","DOI":"10.1523\/JNEUROSCI.4823-07.2007","volume":"27","author":"JJ Repa","year":"2007","unstructured":"Repa JJ, Li H, Frank-Cannon TC, Valasek MA, Turley SD, Tansey MG, et al. Liver X receptor activation enhances cholesterol loss from the brain, decreases neuroinflammation, and increases survival of the NPC1 mouse. J Neurosci. 2007;27(52):14470\u201380.","journal-title":"J Neurosci"},{"issue":"7","key":"8523_CR50","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1161\/01.RES.0000184678.43488.9f","volume":"97","author":"E Rigamonti","year":"2005","unstructured":"Rigamonti E, Helin L, Lestavel S, Mutka AL, Lepore M, Fontaine C, et al. Liver X receptor activation controls intracellular cholesterol trafficking and esterification in human macrophages. Circ Res. 2005;97(7):682\u20139.","journal-title":"Circ Res"},{"issue":"10","key":"8523_CR51","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.7150\/ijbs.35266","volume":"15","author":"Y Feng","year":"2019","unstructured":"Feng Y, Feng F, Zheng C, Zhou Z, Jiang M, Liu Z, et al. Tanshinone IIA attenuates demyelination and promotes remyelination in A. cantonensis-infected BALB\/c mice. Int J Biol Sci. 2019;15(10):2211\u201323.","journal-title":"Int J Biol Sci"},{"issue":"1","key":"8523_CR52","doi-asserted-by":"publisher","first-page":"72","DOI":"10.14336\/AD.2020.0406","volume":"12","author":"S Ping","year":"2021","unstructured":"Ping S, Qiu X, Kyle M, Zhao LR. Brain-derived CCR5 Contributes to Neuroprotection and Brain Repair after Experimental Stroke. Aging Dis. 2021;12(1):72\u201392.","journal-title":"Aging Dis"},{"issue":"1","key":"8523_CR53","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1186\/s40478-018-0628-8","volume":"6","author":"E Grajchen","year":"2018","unstructured":"Grajchen E, Hendriks JJA, Bogie JFJ. The physiology of foamy phagocytes in multiple sclerosis. Acta Neuropathol Commun. 2018;6(1):124.","journal-title":"Acta Neuropathol Commun"},{"issue":"7","key":"8523_CR54","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1016\/j.cell.2009.03.049","volume":"137","author":"HJ Kwon","year":"2009","unstructured":"Kwon HJ, Abi-Mosleh L, Wang ML, Deisenhofer J, Goldstein JL, Brown MS, et al. Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol. Cell. 2009;137(7):1213\u201324.","journal-title":"Cell"},{"issue":"2","key":"8523_CR55","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1097\/00041433-199804000-00010","volume":"9","author":"TF Osborne","year":"1998","unstructured":"Osborne TF, Rosenfeld JM. Related membrane domains in proteins of sterol sensing and cell signaling provide a glimpse of treasures still buried within the dynamic realm of intracellular metabolic regulation. Curr Opin Lipidol. 1998;9(2):137\u201340.","journal-title":"Curr Opin Lipidol"},{"issue":"6","key":"8523_CR56","first-page":"2281","volume":"118","author":"JR Zhang","year":"2008","unstructured":"Zhang JR, Coleman T, Langmade SJ, Scherrer DE, Lane L, Lanier MH, et al. Niemann-Pick C1 protects against atherosclerosis in mice via regulation of macrophage intracellular cholesterol trafficking. J Clin Invest. 2008;118(6):2281\u201390.","journal-title":"J Clin Invest"},{"issue":"6","key":"8523_CR57","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1161\/STROKEAHA.118.024578","volume":"50","author":"C Jing","year":"2019","unstructured":"Jing C, Bian L, Wang M, Keep RF, Xi G, Hua Y. Enhancement of Hematoma Clearance With CD47 Blocking Antibody in Experimental Intracerebral Hemorrhage. Stroke. 2019;50(6):1539\u201347.","journal-title":"Stroke"},{"issue":"1","key":"8523_CR58","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/s41593-020-00757-6","volume":"24","author":"SA Berghoff","year":"2021","unstructured":"Berghoff SA, Spieth L, Sun T, Hosang L, Schlaphoff L, Depp C, et al. Microglia facilitate repair of demyelinated lesions via post-squalene sterol synthesis. Nat Neurosci. 2021;24(1):47\u201360.","journal-title":"Nat Neurosci"},{"key":"8523_CR59","doi-asserted-by":"crossref","unstructured":"Zhu W, Shi R, Li Y, Zhang G, Feng X, Cong J, et al. Stress-induced cholesterol metabolic dysregulation and differentiation trajectory shift in oligodendrocytes synergistically drive demyelination. Int J Mol Sci. 2025;26(8).","DOI":"10.3390\/ijms26083517"},{"key":"8523_CR60","doi-asserted-by":"crossref","unstructured":"Li L, Li R, Zacharek A, Wang F, Landschoot-Ward J, Chopp M, et al. ABCA1\/ApoE\/HDL signaling pathway facilitates myelination and oligodendrogenesis after stroke. Int J Mol Sci. 2020;21(12).","DOI":"10.3390\/ijms21124369"},{"key":"8523_CR61","doi-asserted-by":"crossref","unstructured":"Barnes-V\u00e9lez JA, Zhang X, Pe\u00f1a Se\u00f1eriz YL, Scott KA, Guan Y, Hu J. Peroxisomal integrity in demyelination-associated microglia enables cellular debris clearance and myelin renewal in mice. J Clin Invest. 2026;136(1).","DOI":"10.1172\/JCI179985"},{"issue":"5","key":"8523_CR62","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/j.neuron.2019.12.007","volume":"105","author":"AA Nugent","year":"2020","unstructured":"Nugent AA, Lin K, van Lengerich B, Lianoglou S, Przybyla L, Davis SS, et al. TREM2 Regulates Microglial Cholesterol Metabolism upon Chronic Phagocytic Challenge. Neuron. 2020;105(5):837\u2013e549.","journal-title":"Neuron"},{"issue":"10","key":"8523_CR63","doi-asserted-by":"publisher","first-page":"1138","DOI":"10.1021\/ml500283g","volume":"5","author":"PK Jadhav","year":"2014","unstructured":"Jadhav PK, Schiffler MA, Gavardinas K, Kim EJ, Matthews DP, Staszak MA, et al. Discovery of Cathepsin S Inhibitor LY3000328 for the Treatment of Abdominal Aortic Aneurysm. ACS Med Chem Lett. 2014;5(10):1138\u201342.","journal-title":"ACS Med Chem Lett"},{"issue":"6","key":"8523_CR64","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1111\/bcp.12470","volume":"78","author":"CD Payne","year":"2014","unstructured":"Payne CD, Deeg MA, Chan M, Tan LH, LaBell ES, Shen T, et al. Pharmacokinetics and pharmacodynamics of the cathepsin S inhibitor, LY3000328, in healthy subjects. Br J Clin Pharmacol. 2014;78(6):1334\u201342.","journal-title":"Br J Clin Pharmacol"},{"key":"8523_CR65","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/978-3-7091-0693-8_2","volume":"111","author":"A Manaenko","year":"2011","unstructured":"Manaenko A, Chen H, Zhang JH, Tang J. Comparison of different preclinical models of intracerebral hemorrhage. Acta Neurochir Suppl. 2011;111:9\u201314.","journal-title":"Acta Neurochir Suppl"},{"issue":"1","key":"8523_CR66","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3892\/etm.2022.11719","volume":"25","author":"WS Paiva","year":"2023","unstructured":"Paiva WS, Zippo E, Miranda C, Brasil S, Godoy DA, De Andrade AF, et al. Animal models for the study of intracranial hematomas (Review). Exp Ther Med. 2023;25(1):20.","journal-title":"Exp Ther Med"},{"issue":"6","key":"8523_CR67","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1007\/s12975-020-00830-z","volume":"11","author":"SE Withers","year":"2020","unstructured":"Withers SE, Parry-Jones AR, Allan SM, Kasher PR. A Multi-Model Pipeline for Translational Intracerebral Haemorrhage Research. Transl Stroke Res. 2020;11(6):1229\u201342.","journal-title":"Transl Stroke Res"}],"container-title":["Journal of Translational Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12967-026-08523-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08523-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12967-026-08523-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:13:23Z","timestamp":1786630403000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12967-026-08523-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,30]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["8523"],"URL":"https:\/\/doi.org\/10.1186\/s12967-026-08523-1","relation":{},"ISSN":["1479-5876"],"issn-type":[{"value":"1479-5876","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,30]]},"assertion":[{"value":"1 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 June 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2026","order":6,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":7,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Article updated to include the equal contribution statement of first authors","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal procedures were approved by the Animal Ethics Committee of the Second Affiliated Hospital of Zhejiang University (Approval No. 2024\u2009\u2212\u2009302) and were conducted in accordance with the Guiding Principles for the Care and Use of Laboratory Animals issued by the National Science and Technology Committee of China. All animals (8\u201310 weeks old, 20\u201325\u00a0g) were obtained from Charles River Laboratories (Zhejiang, China; animal license No. XK[Zhe]2024-0001)","order":1,"name":"Ethics","label":"Ethics approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"All authors have read and approved the publication of this manuscript.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"837"}}