{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T02:04:06Z","timestamp":1785895446075,"version":"3.56.0"},"reference-count":88,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Myeloid cells, such as resident microglia (MG), infiltrating monocytes (Mo), macrophages (M\u03a6), and CNS border-associated macrophages (BAM) in the brain, participate in aged brain injury. Aged microglial replacement is protective against brain injury in aged mice; however, whether\/how the molecular changes in myeloid cells are affected by this replacement in injured brains remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Aged microglia in mice were eliminated by PLX3397 for 21 consecutive days and repopulated following withdrawal for 21 days; then, intracerebral hemorrhage (ICH) models were constructed. Then, a single-nucleus transcriptomic analysis of acutely injured brains in aged mice with microglial replacement was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We observed similarities but strong divergence in the composition and molecular change features of myeloid cells between the replacement (Rep) and control (Con) groups, indicating retention of the core transcriptome and development of differential genes in myeloid cells after microglial replacement in response to brain injury. Both MG and Mo\/M\u03a6 experience modification of immune responses after microglial repopulation, with more prominent changes in MG. Gene Ontology (GO) analysis showed that one term directly related to the \u201cimmune response\u201d was shared between upregulated genes in Rep-MG and Rep-Mo\/M\u03a6, while the other terms related to immune functions and other biofunctions were different between Rep-MG and Rep-Mo\/M\u03a6, indicative of significantly different immune responses to brain injury between MG and M\u03a6. Furthermore, the trajectory analysis showed a significant transition from aged to young state in Rep-MG compared to  only  a  modest  youthful shift  in Rep-Mo\/M\u03a6, suggesting a rejuvenation process of aged microglia and macrophages toward young ones in response to brain injury after the treatment of microglial replacement.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our data indicate that microglial replacement-induced changes in the molecular heterogeneity and state transition of myeloid cells may be neuroprotective against acute brain injury.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1625673","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T04:10:48Z","timestamp":1753330248000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Single-nucleus RNA sequencing reveals the specific molecular signatures of myeloid cells responding to brain injury after microglial replacement"],"prefix":"10.3389","volume":"16","author":[{"given":"Xiao-Yi","family":"Xiong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haicheng","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Mu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Shuang","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Xin","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Ru","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Fei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.859067","article-title":"Intracerebral hemorrhage: the effects of aging on brain injury","volume":"14","author":"Watson","year":"2022","journal-title":"Front Aging Neurosci"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12974-019-1516-2","article-title":"Neuroinflammation: friend and foe for ischemic stroke","volume":"16","author":"Jayaraj","year":"2019","journal-title":"J Neuroinflammation"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.108.534503","article-title":"Temporal and spatial dynamics of cerebral immune cell accumulation in stroke","volume":"40","author":"Gelderblom","year":"2009","journal-title":"Stroke"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2013.217","article-title":"Immune cell infiltration in Malignant middle cerebral artery infarction: comparison with transient cerebral ischemia","volume":"34","author":"Chu","year":"2014","journal-title":"J Cereb Blood Flow Metab"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1172\/JCI135530","article-title":"Immune responses to stroke: mechanisms, modulation, and therapeutic potential","volume":"130","author":"Iadecola","year":"2020","journal-title":"J Clin Invest"},{"key":"B6","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s40035-024-00402-3","article-title":"Emerging role of senescent microglia in brain aging-related neurodegenerative diseases","volume":"13","author":"Rim","year":"2024","journal-title":"Transl Neurodegener"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2016.185","article-title":"Microglia priming with aging and stress","volume":"42","author":"Niraula","year":"2017","journal-title":"Neuropsychopharmacology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4597","article-title":"Transcriptomic analysis of purified human cortical microglia reveals age-associated changes","volume":"20","author":"Galatro","year":"2017","journal-title":"Nat Neurosci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4222","article-title":"Microglial brain region-dependent diversity and selective regional sensitivities to aging","volume":"19","author":"Grabert","year":"2016","journal-title":"Nat Neurosci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.12.011","article-title":"Major shifts in glial regional identity are a transcriptional hallmark of human brain aging","volume":"18","author":"Soreq","year":"2017","journal-title":"Cell Rep"},{"key":"B11","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1016\/j.bcp.2014.01.008","article-title":"Microglial dysfunction in brain aging and Alzheimer\u2019s disease","volume":"88","author":"Mosher","year":"2014","journal-title":"Biochem Pharmacol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e12832","DOI":"10.1111\/acel.12832","article-title":"Replacement of microglia in the aged brain reverses cognitive, synaptic, and neuronal deficits in mice","volume":"17","author":"Elmore","year":"2018","journal-title":"Aging Cell"},{"key":"B13","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41419-021-04424-x","article-title":"Microglial replacement in the aged brain restricts neuroinflammation following intracerebral hemorrhage","volume":"13","author":"Li","year":"2022","journal-title":"Cell Death Dis"},{"key":"B14","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1016\/j.immuni.2018.01.011","article-title":"High-dimensional single-cell mapping of central nervous system immune cells reveals distinct myeloid subsets in health, aging, and disease","volume":"48","author":"Mrdjen","year":"2018","journal-title":"Immunity"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0654-0","article-title":"Transcriptional profiling and therapeutic targeting of oxidative stress in neuroinflammation","volume":"21","author":"Mendiola","year":"2020","journal-title":"Nat Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat7554","article-title":"Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation","volume":"363","author":"Jord\u00e3o","year":"2019","journal-title":"Science"},{"key":"B17","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.immuni.2018.11.004","article-title":"Single-cell RNA sequencing of microglia throughout the mouse lifespan and in the injured brain reveals complex cell-state changes","volume":"50","author":"Hammond","year":"2019","journal-title":"Immunity"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1016\/j.cell.2017.05.018","article-title":"A unique microglia type associated with restricting development of Alzheimer\u2019s disease","volume":"169","author":"Keren-Shaul","year":"2017","journal-title":"Cell"},{"key":"B19","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1177\/0271678X211026770","article-title":"Single-cell RNA-seq reveals the transcriptional landscape in ischemic stroke","volume":"42","author":"Zheng","year":"2022","journal-title":"J Cereb Blood Flow Metab"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1527","DOI":"10.1016\/j.immuni.2021.04.022","article-title":"Treg cell-derived osteopontin promotes microglia-mediated white matter repair after ischemic stroke","volume":"54","author":"Shi","year":"2021","journal-title":"Immunity"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.02.040","article-title":"Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain","volume":"82","author":"Elmore","year":"2014","journal-title":"Neuron"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-021-01144-w","article-title":"Deep succinylproteomics of brain tissues from intracerebral hemorrhage with inhibition of toll-like receptor 4 signaling","volume":"42","author":"Liang","year":"2022","journal-title":"Cell Mol Neurobiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"168","DOI":"10.31083\/j.jin2206168","article-title":"PKM2 nuclear translocation promotes glial cell activation and aggravates the brain injury of intracerebral hemorrhage","volume":"22","author":"Xiong","year":"2023","journal-title":"J Integr Neurosci"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.021881","article-title":"Toll-like receptor 4\/myD88-mediated signaling of hepcidin expression causing brain iron accumulation, oxidative injury, and cognitive impairment after intracerebral hemorrhage","volume":"134","author":"Xiong","year":"2016","journal-title":"Circulation"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.cell.2019.05.031","article-title":"Comprehensive integration of single-cell data","volume":"177","author":"Stuart","year":"2019","journal-title":"Cell"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4096","article-title":"Integrating single-cell transcriptomic data across different conditions, technologies, and species","volume":"36","author":"Butler","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1126\/science.aad0501","article-title":"Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq","volume":"352","author":"Tirosh","year":"2016","journal-title":"Science"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"Omics"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2859","article-title":"The dynamics and regulators of cell fate decisions are revealed by pseudotemporal ordering of single cells","volume":"32","author":"Trapnell","year":"2014","journal-title":"Nat Biotechnol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1038\/s41586-019-0969-x","article-title":"The single-cell transcriptional landscape of mammalian organogenesis","volume":"566","author":"Cao","year":"2019","journal-title":"Nature"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e1005079","DOI":"10.1371\/journal.pgen.1005079","article-title":"Escape from X inactivation varies in mouse tissues","volume":"11","author":"Berletch","year":"2015","journal-title":"PloS Genet"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e2250233","DOI":"10.1002\/eji.202250233","article-title":"Macrophage and monocyte subsets in response to ischemic stroke","volume":"53","author":"Blank-Stein","year":"2023","journal-title":"Eur J Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13899","article-title":"Phagocytic microglia and macrophages in brain injury and repair","volume":"28","author":"Yu","year":"2022","journal-title":"CNS Neurosci Ther"},{"key":"B34","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.pneurobio.2016.05.001","article-title":"Functions and mechanisms of microglia\/macrophages in neuroinflammation and neurogenesis after stroke","volume":"142","author":"Xiong","year":"2016","journal-title":"Prog Neurobiol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1038\/s41467-021-21407-w","article-title":"Single-cell RNA sequencing reveals functional heterogeneity of glioma-associated brain macrophages","volume":"12","author":"Ochocka","year":"2021","journal-title":"Nat Commun"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-023-01257-z","article-title":"Perivascular cells induce microglial phagocytic states and synaptic engulfment via SPP1 in mouse models of Alzheimer\u2019s disease","volume":"26","author":"De Schepper","year":"2023","journal-title":"Nat Neurosci"},{"key":"B37","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1016\/j.jneuroim.2024.578411","article-title":"Co-localization and co-expression of Olfml3 with Iba1 in brain of mice","author":"Yadav","year":"2024","journal-title":"J Neuroimmunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-5728(01)00240-5","article-title":"CD81 and microglial activation in vitro: proliferation, phagocytosis and nitric oxide production","volume":"114","author":"Dijkstra","year":"2001","journal-title":"J Neuroimmunol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0707-4","article-title":"Novel Hexb-based tools for studying microglia in the CNS","volume":"21","author":"Masuda","year":"2020","journal-title":"Nat Immunol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0393-4","article-title":"A single-cell atlas of mouse brain macrophages reveals unique transcriptional identities shaped by ontogeny and tissue environment","volume":"22","author":"Van Hove","year":"2019","journal-title":"Nat Neurosci"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3554","article-title":"The microglial sensome revealed by direct RNA sequencing","volume":"16","author":"Hickman","year":"2013","journal-title":"Nat Neurosci"},{"key":"B42","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1038\/s41467-022-28593-1","article-title":"Stroke induces disease-specific myeloid cells in the brain parenchyma and pia","volume":"13","author":"Beuker","year":"2022","journal-title":"Nat Commun"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-0768-4","article-title":"Limited proliferation capacity of aortic intima resident macrophages requires monocyte recruitment for atherosclerotic plaque progression","volume":"21","author":"Williams","year":"2020","journal-title":"Nat Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22885","article-title":"Macrophage-derived osteopontin induces reactive astrocyte polarization and promotes re-establishment of the blood brain barrier after ischemic stroke","volume":"63","author":"Gliem","year":"2015","journal-title":"Glia"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1111\/ene.13496","article-title":"Galectin-3: an emerging biomarker in stroke and cerebrovascular diseases","volume":"25","author":"Venkatraman","year":"2018","journal-title":"Eur J Neurol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1016\/j.cell.2019.05.054","article-title":"Lipid-associated macrophages control metabolic homeostasis in a trem2-dependent manner","volume":"178","author":"Jaitin","year":"2019","journal-title":"Cell"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-023-01711-x","article-title":"Analysis of brain and blood single-cell transcriptomics in acute and subacute phases after experimental stroke","volume":"25","author":"Garcia-Bonilla","year":"2024","journal-title":"Nat Immunol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13701","article-title":"Production of MHCII-expressing classical monocytes increases during aging in mice and humans","volume":"21","author":"Barman","year":"2022","journal-title":"Aging Cell"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.953730","article-title":"Activation mechanisms of monocytes\/macrophages in adult-onset Still disease","volume":"13","author":"Tsuboi","year":"2022","journal-title":"Front Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9861(20001211)428:2<266::AID-CNE6>3.0.CO;2-0","article-title":"Up-regulation of CD81 (target of the antiproliferative antibody; TAPA) by reactive microglia and astrocytes after spinal cord injury in the rat","volume":"428","author":"Dijkstra","year":"2000","journal-title":"J Comp Neurol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.59.2.172","article-title":"Lipopolysaccharide regulates cysteine-rich intestinal protein, a zinc-finger protein, in immune cells and plasma","volume":"59","author":"Hallquist","year":"1996","journal-title":"J Leukoc Biol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1042\/CS20201372","article-title":"CRIP1 expression in monocytes related to hypertension","volume":"135","author":"Schweigert","year":"2021","journal-title":"Clin Sci (Lond)"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.09458","article-title":"Transcriptome-wide analysis identifies novel associations with blood pressure","volume":"70","author":"Zeller","year":"2017","journal-title":"Hypertension"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0982-08.2008","article-title":"CD36\/fatty acid translocase, an inflammatory mediator, is involved in hyperlipidemia-induced exacerbation in ischemic brain injury","volume":"28","author":"Kim","year":"2008","journal-title":"J Neurosci"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20170277","article-title":"CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes","volume":"216","author":"Rapp","year":"2019","journal-title":"J Exp Med"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3205","article-title":"Active secretion of CXCL10 and CCL5 from colorectal cancer microenvironments associates with GranzymeB+ CD8+ T-cell infiltration","volume":"6","author":"Zumwalt","year":"2015","journal-title":"Oncotarget"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90173-6","article-title":"A sulfated peptide segment at the amino terminus of PSGL-1 is critical for P-selectin binding","volume":"83","author":"Sako","year":"1995","journal-title":"Cell"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.318022","article-title":"Ezrin-radixin-moesin-binding sequence of PSGL-1 glycoprotein regulates leukocyte rolling on selectins and activation of extracellular signal-regulated kinases","volume":"287","author":"Spertini","year":"2012","journal-title":"J Biol Chem"},{"key":"B59","doi-asserted-by":"publisher","first-page":"28997","DOI":"10.1038\/srep28997","article-title":"Psgl-1 deficiency is protective against stroke in a murine model of lupus","volume":"6","author":"Wang","year":"2016","journal-title":"Sci Rep"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-017-1795-6","article-title":"Distinguishing features of microglia- and monocyte-derived macrophages after stroke","volume":"135","author":"Kronenberg","year":"2018","journal-title":"Acta Neuropathol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1186\/s12974-024-03242-0","article-title":"Tracking changes in functionality and morphology of repopulated microglia in young and old mice","volume":"21","author":"Luczak-Sobotkowska","year":"2024","journal-title":"J Neuroinflammation"},{"key":"B62","doi-asserted-by":"publisher","first-page":"74","DOI":"10.2174\/138945013804806505","article-title":"Neuroprotection & mechanism of ethanol in stroke and traumatic brain injury therapy: new prospects for an ancient drug","volume":"14","author":"Asmaro","year":"2013","journal-title":"Curr Drug Targets"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2302892120","article-title":"Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo","volume":"120","author":"Boghozian","year":"2023","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1007\/s11481-014-9560-2","article-title":"Pro-inflammatory interferon gamma signaling is directly associated with stroke induced neurodegeneration","volume":"9","author":"Seifert","year":"2014","journal-title":"J Neuroimmune Pharmacol"},{"key":"B65","doi-asserted-by":"publisher","first-page":"126","DOI":"10.3390\/v11020126","article-title":"Antiviral role of IFITM proteins in classical swine fever virus infection","volume":"11","author":"Li","year":"2019","journal-title":"Viruses"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.120.030429","article-title":"Infection as a stroke risk factor and determinant of outcome after stroke","volume":"51","author":"Elkind","year":"2020","journal-title":"Stroke"},{"key":"B67","doi-asserted-by":"publisher","first-page":"112473","DOI":"10.1016\/j.intimp.2024.112473","article-title":"Microglial repopulation induced by PLX3397 protects against ischemic brain injury by suppressing neuroinflammation in aged mice","volume":"138","author":"Li","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B68","doi-asserted-by":"publisher","first-page":"3485","DOI":"10.3390\/ijms23073485","article-title":"The role of CCL2\/CCR2 axis in cerebral ischemia-reperfusion injury and treatment: from animal experiments to clinical trials","volume":"23","author":"Geng","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B69","doi-asserted-by":"publisher","first-page":"858","DOI":"10.3390\/diagnostics12040858","article-title":"Tubulin alpha 1b is associated with the immune cell infiltration and the response of HCC patients to immunotherapy","volume":"12","author":"Hu","year":"2022","journal-title":"Diagnostics"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu238","article-title":"TUBB5 and its disease-associated mutations influence the terminal differentiation and dendritic spine densities of cerebral cortical neurons","volume":"23","author":"Ngo","year":"2014","journal-title":"Hum Mol Genet"},{"key":"B71","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1007\/s10637-021-01197-0","article-title":"STMN1 is highly expressed and contributes to clonogenicity in acute promyelocytic leukemia cells","volume":"40","author":"Vicari","year":"2022","journal-title":"Invest New Drugs"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.05.003","article-title":"Disease-associated microglia: A universal immune sensor of neurodegeneration","volume":"173","author":"Deczkowska","year":"2018","journal-title":"Cell"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab260","article-title":"RVAgene: generative modeling of gene expression time series data","volume":"37","author":"Mitra","year":"2021","journal-title":"Bioinformatics"},{"key":"B74","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s40478-018-0581-6","article-title":"CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage","volume":"6","author":"Pedragosa","year":"2018","journal-title":"Acta Neuropathol Commun"},{"key":"B75","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s13024-023-00660-1","article-title":"Border-associated macrophages promote cerebral amyloid angiopathy and cognitive impairment through vascular oxidative stress","volume":"18","author":"Uekawa","year":"2023","journal-title":"Mol Neurodegener"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.851556","article-title":"PLX5622 reduces disease severity in lethal CNS infection by off-target inhibition of peripheral inflammatory monocyte production","volume":"13","author":"Spiteri","year":"2022","journal-title":"Front Immunol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-1816","article-title":"Inhibition of CSF-1 receptor improves the antitumor efficacy of adoptive cell transfer immunotherapy","volume":"74","author":"Mok","year":"2014","journal-title":"Cancer Res"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.4103\/NRR.NRR-D-24-01092","article-title":"Changes in border-associated macrophages after stroke: Single-cell sequencing analysis","volume":"21","author":"Yu","year":"2026","journal-title":"Neural Regener Res"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40478-018-0581-6","article-title":"CNS-border associated macrophages respond to acute ischemic stroke attracting granulocytes and promoting vascular leakage","volume":"6","author":"Pedragosa","year":"2018","journal-title":"Acta Neuropathol Commun"},{"key":"B80","doi-asserted-by":"publisher","first-page":"108220","DOI":"10.1016\/j.pharmthera.2022.108220","article-title":"CNS border-associated macrophages in the homeostatic and ischaemic brain","volume":"240","author":"Gerganova","year":"2022","journal-title":"Pharmacol Ther"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2017.69","article-title":"Modulators of microglial activation and polarization after intracerebral haemorrhage","volume":"13","author":"Lan","year":"2017","journal-title":"Nat Rev Neurol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2021.09.024","article-title":"Translocator protein regulate polarization phenotype transformation of microglia after cerebral ischemia-reperfusion injury","volume":"480","author":"Yusuying","year":"2022","journal-title":"Neuroscience"},{"key":"B83","doi-asserted-by":"publisher","first-page":"2722","DOI":"10.1016\/j.molcel.2021.05.005","article-title":"Choline kinase alpha 2 acts as a protein kinase to promote lipolysis of lipid droplets","volume":"81","author":"Liu","year":"2021","journal-title":"Mol Cell"},{"key":"B84","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1038\/s41593-019-0566-1","article-title":"Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain","volume":"23","author":"Marschallinger","year":"2020","journal-title":"Nat Neurosci"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07185-7","article-title":"APOE4\/4 is linked to damaging lipid droplets in Alzheimer\u2019s disease microglia","volume":"628","author":"Haney","year":"2024","journal-title":"Nature"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.595","article-title":"Serum Markers After Spontaneous Cerebral Hemorrhage I. CCL2 and CXCL10 are associated with poor outcome after intracerebral hemorrhage","volume":"5","author":"Landreneau","year":"2018","journal-title":"Ann Clin Transl Neurol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00079.2024","article-title":"CXCL10 impairs synaptic plasticity and was modulated by cGAS-STING pathway after stroke in mice","volume":"132","author":"Wang","year":"2024","journal-title":"J Neurophysiol"},{"key":"B88","doi-asserted-by":"publisher","first-page":"786","DOI":"10.14336\/AD.2020.0926","article-title":"Genome-wide screen and validation of microglia pro-inflammatory mediators in stroke","volume":"12","author":"Wu","year":"2021","journal-title":"Aging Dis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1625673\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T04:10:49Z","timestamp":1753330249000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1625673\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,24]]},"references-count":88,"alternative-id":["10.3389\/fimmu.2025.1625673"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1625673","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,24]]},"article-number":"1625673"}}