The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Macrophages prevent hemorrhagic infarct transformation in murine stroke models
Abstract
Objective: Inflammation is increasingly viewed as a new therapeutic target in subacute stages of brain infarction. However, apart from causing secondary damage, inflammation could equally promote beneficial lesion remodeling and repair. Distinct subpopulations of monocytes/macrophages (MOs/MPs) may critically determine the outcome of lesion‐associated inflammation. Methods: We addressed the role of bone marrow‐derived MOs/MPs in 2 different mouse models of ischemic stroke using a combined cell‐specific depletion, chemokine receptor knockout, bone marrow chimeric, and pharmacological approach. Results: Starting within 24 hours of stroke onset, immature Ly6c hi monocytes infiltrated into the infarct border zone and differentiated into mature Ly6c lo phagocytes within the lesion compartment. MO/MP infiltration was CCR2‐dependent, whereas we did not obtain evidence for additional recruitment via CX3CR1. Depletion of circulating MOs/MPs or selective targeting of CCR2 in bone marrow‐derived cells caused delayed clinical deterioration and hemorrhagic conversion of the infarctions. Bleeding frequently occurred around thin‐walled, dilated neovessels in the infarct border zone and was accompanied by decreased expression of transforming growth factor (TGF)‐β1 and collagen‐4, along with diminished activation of Smad2. Injection of TGF‐β1 into the lesion border zone greatly reduced infarct bleeding in MO/MP‐depleted mice. Interpretation: Bone marrow‐derived MOs/MPs recruited via CCR2 and acting via TGF‐β1 are essential for maintaining integrity of the neurovascular unit following brain ischemia. Future therapies should be aimed at enhancing physiological repair functions of CCR2+ MOs/MPs rather than blocking their hematogenous recruitment. ANN NEUROL 2012;71:743–752
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“demonstrating the importance of these cells in healing after stroke”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [127]
In the citing paper
“In CCR2-deficient mice or following early monocyte depletion by clodronate liposomes in stroke, the resultant reduced expression of tissue repair proteins, including TGF-β1 and collagen-4, was associated with neurovascular unit instability and later haemorrhagic transformation [127]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [127]
In the citing paper
“However, depletion of these cells has a negative impact on stroke outcome and increases the incidence of hemorrhagic transformation (146).”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [146]
In the citing paper
“Pro-inflammatory monocytes eventually follow neutrophils into the brain parenchyma and enter in a CCR2-dependent manner, eventually differentiating into Ly6Clow phagocytes.”
From The anatomy and immunology of vasculature in the central nervous system (2019) · cites this paper as [146]
Citations
Cites
Exploring the full spectrum of macrophage activation
Mosser, D. M., & Edwards, J. P. (2008) · Nature Reviews Immunology · doi:10.1038/nri2448 · Cited by 9,144
Monocyte and macrophage heterogeneity
Gordon, S., & Taylor, P. R. (2005) · Nature Reviews Immunology · doi:10.1038/nri1733 · Cited by 5,190
Blood Monocytes Consist of Two Principal Subsets with Distinct Migratory Properties
Geissmann, F., Jung, S., & Littman, D. R. (2003) · Immunity · doi:10.1016/s1074-7613(03)00174-2 · Cited by 3,504
The immunology of stroke: from mechanisms to translation
Iadecola, C., & Anrather, J. (2011) · Nature Medicine · doi:10.1038/nm.2399 · Cited by 2,596
Nahrendorf, M., Swirski, F. K., Aikawa, E., Stangenberg, L., Wurdinger, T., Figueiredo, J.-L., Libby, P., Weissleder, R., & Pittet, M. J. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070885 · Cited by 2,300
Lees, K., Bluhmki, E., von Kummer, R., Brott, T., Toni, D., Grotta, J., Albers, G., Kaste, M., Marler, J., Hamilton, S., et al. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60491-6 · Cited by 2,182
Kigerl, K. A., Gensel, J. C., Ankeny, D. P., Alexander, J. K., Donnelly, D. J., & Popovich, P. G. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.3257-09.2009 · Cited by 2,130
Arnold, L., Henry, A., Poron, F., Baba-Amer, Y., van Rooijen, N., Plonquet, A., Gherardi, R. K., & Chazaud, B. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070075 · Cited by 2,002
Mechanisms, challenges and opportunities in stroke
Lo, E. H., Dalkara, T., & Moskowitz, M. A. (2003) · Nature reviews. Neuroscience · doi:10.1038/nrn1106 · Cited by 1,808
van Rooijen, N., & Sanders, A. (1994) · Journal of Immunological Methods · doi:10.1016/0022-1759(94)90012-4 · Cited by 1,763
Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair
Duffield, J. S., Forbes, S. J., Constandinou, C. M., Clay, S., Partolina, M., Vuthoori, S., Wu, S., Lang, R., & Iredale, J. P. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200522675 · Cited by 1,649
Differential Roles of Macrophages in Diverse Phases of Skin Repair
Lucas, T., Waisman, A., Ranjan, R., Roes, J., Krieg, T., Müller, W., Roers, A., & Eming, S. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903356 · Cited by 1,205
New insights into TGF-β–Smad signalling
ten Dijke, P., & Hill, C. S. (2004) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2004.03.008 · Cited by 1,176
Thrombospondin-1 Is a Major Activator of TGF-β1 In Vivo
Crawford, S. E., Stellmach, V. M., Murphy-Ullrich, J. E., Ribeiro, S. M. F., Lawler, J., Hynes, R. O., Boivin, G. P., & Bouck, N. (1998) · Cell · doi:10.1016/s0092-8674(00)81460-9 · Cited by 1,176
Microglia in the adult brain arise from Ly-6ChiCCR2+ monocytes only under defined host conditions
Mildner, A., Schmidt, H., Nitsche, M., Merkler, D., Hanisch, U.-K., Mack, M., Heikenwalder, M., Brück, W., Priller, J., & Prinz, M. (2007) · Nature Neuroscience · doi:10.1038/nn2015 · Cited by 1,089
Shechter, R., London, A., Varol, C., Raposo, C., Cusimano, M., Yovel, G., Rolls, A., Mack, M., Pluchino, S., Martino, G., et al. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000113 · Cited by 770
Sedgwick, J. D., Schwender, S., Imrich, H., Dörries, R., Butcher, G. W., & ter Meulen, V. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.16.7438 · Cited by 691
van Amerongen, M. J., Harmsen, M. C., van Rooijen, N., Petersen, A. H., & van Luyn, M. J. A. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.060547 · Cited by 544
Mildner, A., Mack, M., Schmidt, H., Brück, W., Djukic, M., Zabel, M. D., Hille, A., Priller, J., & Prinz, M. (2009) · Brain · doi:10.1093/brain/awp144 · Cited by 445
Absence of the Chemokine Receptor CCR2 Protects Against Cerebral Ischemia/Reperfusion Injury in Mice
Dimitrijevic, O. B., Stamatovic, S. M., Keep, R. F., & Andjelkovic, A. V. (2007) · Stroke · doi:10.1161/01.str.0000259709.16654.8f · Cited by 368
Getts, D. R., Terry, R. L., Getts, M. T., Müller, M., Rana, S., Shrestha, B., Radford, J., Van Rooijen, N., Campbell, I. L., & King, N. J. C. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080421 · Cited by 360
Monofilament intraluminal middle cerebral artery occlusion in the mouse
Clark, W. M., Lessov, N. S., Dixon, M., & Eckenstein, F. P. (1997) · Neurological Research · doi:10.1080/01616412.1997.11740874 · Cited by 287
Lu, H., Huang, D., Saederup, N., Charo, I. F., Ransohoff, R. M., & Zhou, L. (2010) · The FASEB Journal · doi:10.1096/fj.10-171579 · Cited by 279
Dénes, Á., Ferenczi, S., Halász, J., Környei, Z., & Kovács, K. J. (2008) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2008.64 · Cited by 276
Li, F., Lan, Y., Wang, Y., Wang, J., Yang, G., Meng, F., Han, H., Meng, A., Wang, Y., & Yang, X. Y. (2011) · Developmental Cell · doi:10.1016/j.devcel.2011.01.011 · Cited by 268
Effects of the Chemokine CCL2 on Blood–Brain Barrier Permeability during Ischemia–Reperfusion Injury
Dimitrijevic, O. B., Stamatovic, S. M., Keep, R. F., & Andjelkovic, A. V. (2006) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600229 · Cited by 252
Bauer, J., Huitinga, I., Zhao, W., Lassmann, H., Hickey, W. F., & Dijkstra, C. D. (1995) · Glia · doi:10.1002/glia.440150407 · Cited by 226
Donnelly, D. J., Longbrake, E. E., Shawler, T. M., Kigerl, K. A., Lai, W., Tovar, C. A., Ransohoff, R. M., & Popovich, P. G. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2114-11.2011 · Cited by 219
Triggers and Mediators of Hemorrhagic Transformation in Cerebral Ischemia
Wang, X., & Lo, E. H. (2003) · Molecular Neurobiology · doi:10.1385/mn:28:3:229 · Cited by 210
Monocyte Subtypes Predict Clinical Course and Prognosis in Human Stroke
Urra, X., Villamor, N., Amaro, S., Gómez-Choco, M. J., Obach, V., Oleaga, L., Planas, A. M., & Chamorro, Á. (2009) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2009.25 · Cited by 203
Henrich-Noack, P., Prehn, J. H. M., & Krieglstein, J. (1996) · Stroke · doi:10.1161/01.str.27.9.1609 · Cited by 202
Conditional ablation of macrophages disrupts ovarian vasculature
Turner, E. C., Hughes, J., Wilson, H., Clay, M., Mylonas, K. J., Kipari, T. M. J., Duncan, W. C., & Fraser, H. M. (2011) · Reproduction · doi:10.1530/rep-10-0327 · Cited by 124
Visualization of Chemokine Binding Sites on Human Brain Microvessels
Andjelkovic, A. V., Spencer, D. D., & Pachter, J. S. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.2.403 · Cited by 83
Inflammatory gene expression in focal cortical brain ischemia: differences between rats and mice
Schroeter, M., Küry, P., & Jander, S. (2003) · Molecular Brain Research · doi:10.1016/s0169-328x(03)00255-9 · Cited by 64
Self-citationYokochi, S., Hashimoto, H., Ishiwata, Y., Shimokawa, H., Haino, M., Terashima, Y., & Matsushima, K. (2001) · Journal of Interferon & Cytokine Research · doi:10.1089/107999001750277862 · Cited by 63
Inflammation in Stroke: The Good, the Bad, and the Unknown
Dirnagl, U. (2004) · Springer eBooks · doi:10.1007/978-3-662-05426-0_5 · Cited by 58
Thanvi, B., Treadwell, S. D., & Robinson, T. G. (2008) · Postgraduate Medical Journal · doi:10.1136/pgmj.2007.067058 · Cited by 54
Mausberg, A. K., Jander, S., & Reichmann, G. (2009) · Glia · doi:10.1002/glia.20853 · Cited by 32
Self-citationAdvances in Translational Medicine 2010
Planas, A. M., & Traystman, R. J. (2011) · Stroke · doi:10.1161/strokeaha.110.605055 · Cited by 12
Cited by
Sorted by citations
Neuroinflammation: friend and foe for ischemic stroke
Jayaraj, R. L., Azimullah, S., Beiram, R., Jalal, F. Y., & Rosenberg, G. A. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1516-2 · Cited by 1,479
Yang, J., Zhang, L., Yu, C., Yang, X.-F., & Wang, H. (2014) · Biomarker Research · doi:10.1186/2050-7771-2-1 · Cited by 1,099
Inflammation and Stroke: An Overview
Anrather, J., & Iadecola, C. (2016) · Neurotherapeutics · doi:10.1007/s13311-016-0483-x · Cited by 966
Immune responses to stroke: mechanisms, modulation, and therapeutic potential.
Iadecola, C., Buckwalter, M. S., & Anrather, J. (2020) · Journal of Clinical Investigation · doi:10.1172/jci135530 · Cited by 853
The contribution of astrocytes and microglia to traumatic brain injury
Karve, I. P., Taylor, J. M., & Crack, P. J. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13125 · Cited by 675
Metadata
- Authors
- Gliem, M., Mausberg, A. K., Lee, J., Simiantonakis, I., van Rooijen, N., Hartung, H., & Jander, S.
- Affiliations
- Heinrich Heine University Düsseldorf (DE)
- Corresponding author
- Jander, Sebastian
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2012-06
- Volume
- 71
- Issue
- 6
- Pages
- 743-752
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2122031395
- Cited by
- 284
- References
- 39
- Citations by year
- 2026: 8 · 2025: 19 · 2024: 19 · 2023: 16 · 2022: 29 · 2021: 19 · 2020: 25 · 2019: 14 · 2018: 21 · 2017: 19 · 2016: 31 · 2015: 29 · 2014: 15 · 2013: 17 · 2012: 3
- FWCI
- 10.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
- Health Sciences › Medicine › Clinical Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- macrophages, monocytes, ischemic stroke, hemorrhagic transformation, CCR2, TGF-β1, Smad2, neurovascular unit, infarct border zone, bone marrow-derived cells, cell depletion, CX3CR1
- MeSH terms
- CX3C Chemokine Receptor 1, CD68 Molecule, Animals, Antigens, Ly, Cell Differentiation, Diphtheria Toxin, Disease Models, Animal, Drug Administration Routes, Flow Cytometry, Gene Expression Regulation, Germanium, Interferon Inducers, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity, Organometallic Compounds, Propionates, Time Factors, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Leukocyte Common Antigens, Receptors, Chemokine, Infarction, Middle Cerebral Artery, Intracranial Hemorrhages, Brain Infarction, Stroke, Intracranial Thrombosis, Intercellular Signaling Peptides and Proteins, CD11b Antigen, Mice, Transforming Growth Factor beta1, Receptors, CCR2, Heparin-binding EGF-like Growth Factor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
