Turnover of Rat Brain Perivascular Cells
Abstract
Brain perivascular spaces harbor a population of cells which exhibit high phagocytic capacity. Therefore, these cells can be labeled by intraventricular injection of tracers. Such perivascular cells at the interface between blood and brain are believed to belong to the monocyte/macrophage lineage and to be involved in antigen presentation. Currently, it is unclear whether these cells undergo a continuous turnover by entering and leaving the bloodstream. Using bone-marrow-chimeric animals, migration of donor macrophages into brain perivascular spaces has been reported. On the other hand, following intracerebral injection of india ink into nontransplanted animals, ink-labeled perivascular cells were still found 2 years after injection, suggesting a high stability of this cell pool. Thus, the turnover of perivascular cells observed in chimeras might be a result of bone marrow transplantation rather than a physiological occurrence. To address this issue, we monitored de novo invasion of macrophages into perivascular spaces of apparently healthy adult rats by applying techniques other than bone marrow transplantation, (i) consecutive injections of different tracers and (ii) ex vivo isolation of macrophages from the blood, cell labeling, and reinjection into the same animal to avoid MHC mismatch. Both approaches revealed vivid de novo invasion of macrophages into perivascular spaces, but not into brain parenchyma, rendering untenable the concept of perivascular cells forming a stable population of macrophages in the brain. Thus, brain perivascular spaces are under permanent immune surveillance of blood borne macrophages in normal adult rats.
Integrity signals
Registry
Cites
Statistics
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?
PVMs are resident brain macrophages located in the intracerebral perivascular space, closely apposed to the outer vessel wall, and derived from hematopoietic precursors.
“Residing in the intracerebral perivascular space, delimited by the glia limitans and the vascular basement membrane (Virchow-Robin space), PVMs are closely apposed to the outer vessel wall and originate from hematopoietic precursors (18,20,21).”
From Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension (2016) · cites this paper as [20]
Brain PVMs are myeloid cells closely associated with the abluminal side of cerebral blood vessels, express the mannose receptor CD206, express low levels of IBA1 relative to microglia, and are phagocytic.
“Brain PVMs were identified as myeloid cells closely associated with the abluminal side of cerebral blood vessels and (a) expressing the mannose receptor CD206 (Figure 1 1D); (c) expressing low levels of IBA1, compared with microglial cells (Figure 1C); and (d) endowed of phagocytic activity assessed by injection of dextran into the lateral ventricles (Figure 1, B-D, and ref. 26).”
From Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension (2016) · cites this paper as [26]
Cites
Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo
Hickey, W. F., & Kimura, H. (1988) · Science · doi:10.1126/science.3276004 · Cited by 1,466 · see citing works
Astrocyte glutamate transport: Review of properties, regulation, and physiological functions
Anderson, C. M., & Swanson, R. A. (2000) · Glia · doi:10.1002/1098-1136(200010)32:1 · Cited by 1,218 · see citing works
T‐lymphocyte entry into the central nervous system
Hickey, W. F., Hsu, B. L., & Kimura, H. (1991) · Journal of Neuroscience Research · doi:10.1002/jnr.490280213 · Cited by 1,176 · see citing works
Hickey, W. F., Vass, K., & Lassmann, H. (1992) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199205000-00002 · Cited by 401 · see citing works
Unique monocyte subset in patients with AIDS dementia
Pulliam, L., Gascon, R., Stubblebine, M., McGuire, D., & McGrath, M. S. (1997) · The Lancet · doi:10.1016/s0140-6736(96)10178-1 · Cited by 375 · see citing works
Graeber, M. B., Streit, W. J., & Kreutzberg, G. W. (1988) · Journal of Neuroscience Research · doi:10.1002/jnr.490210104 · Cited by 367 · see citing works
Bone marrow derived elements and resident microglia in brain inflammation
Lassmann, H., Schmied, M. C., Vass, K., & Hickey, W. F. (1993) · Glia · doi:10.1002/glia.440070106 · Cited by 349 · see citing works
Kennedy, D. W., & Abkowitz, J. L. (1997) · Blood · doi:10.1182/blood.v90.3.986 · Cited by 342 · see citing works
Brain macrophages: on the role of pericytes and perivascular cells
Thomas, W. E. (1999) · Brain Research Reviews · doi:10.1016/s0165-0173(99)00024-7 · Cited by 306 · see citing works
Streit, W. J., Graeber, M. B., & Kreutzberg, G. W. (1989) · Experimental Neurology · doi:10.1016/0014-4886(89)90111-8 · Cited by 287 · see citing works
Identity of ED2‐positive perivascular cells in rat brain
Graeber, M. B., Streit, W. J., & Kreutzberg, G. W. (1989) · Journal of Neuroscience Research · doi:10.1002/jnr.490220114 · Cited by 280 · see citing works
Mast Cells Migrate from Blood to Brain
Silverman, A.-J., Sutherland, A. K., Wilhelm, M., & Silver, R. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-01-00401.2000 · Cited by 228 · see citing works
Bauer, J., Huitinga, I., Zhao, W., Lassmann, H., Hickey, W. F., & Dijkstra, C. D. (1995) · Glia · doi:10.1002/glia.440150407 · Cited by 226 · see citing works
Cellular mechanisms of CNS pericytes
Rucker, H. K., Wynder, H. J., & Thomas, W. E. (2000) · Brain Research Bulletin · doi:10.1016/s0361-9230(99)00260-9 · Cited by 220 · see citing works
Distribution of extracellular tracers in perivascular spaces of the rat brain
Ichimura, T., Fraser, P. A., & Cserr, H. F. (1991) · Brain Research · doi:10.1016/0006-8993(91)91275-6 · Cited by 215 · see citing works
Zhang, E. T., Richards, H. K., Kida, S., & Weller, R. O. (1992) · Acta Neuropathologica · doi:10.1007/bf00296784 · Cited by 205 · see citing works
Kida, S., Steart, P. V., Zhang, E.-T., & Weller, R. O. (1993) · Acta Neuropathologica · doi:10.1007/bf00334675 · Cited by 189 · see citing works
Male Donor-derived Cells in the Brains of Female Sex-mismatched Bone Marrow Transplant Recipients
Unger, E. R., SUNG, J. H., Manivel, J. C., Chenggis, M. L., Blazar, B. R., & Krivit, W. A. (1993) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199309000-00004 · Cited by 187 · see citing works
Mato, M., Ookawara, S., Sakamoto, A., Aikawa, E., Ogawa, T., Mitsuhashi, U., Masuzawa, T., Suzuki, H., Honda, M., Yazaki, Y., et al. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.8.3269 · Cited by 187 · see citing works
You, S., Petrov, T., Chung, P. H., & Gordon, T. (1997) · Glia · doi:10.1002/(sici)1098-1136(199706)20:2 · Cited by 172 · see citing works
Krall, W. J., Challita, P. M., Perlmutter, L., Skelton, D. C., & Kohn, D. B. (1994) · Blood · doi:10.1182/blood.v83.9.2737.2737 · Cited by 163 · see citing works
Streit, W. J., & Graeber, M. B. (1993) · Glia · doi:10.1002/glia.440070112 · Cited by 159 · see citing works
Graeber, M. B., Streit, W. J., Büringer, D., Sparks, D. L., & Kreutzberg, G. W. (1992) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199205000-00009 · Cited by 149 · see citing works
Harling‐Berg, C. J., Park, J. T., & Knopf, P. M. (1999) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(99)00130-7 · Cited by 134 · see citing works
Groot, C. J. A. D., Huppes, W., Sminia, T., Kraal, G., & Dijkstra, C. D. (1992) · Glia · doi:10.1002/glia.440060408 · Cited by 120 · see citing works
Perivascular microglia defined
Graeber, M. B., & Streit, W. J. (1990) · Trends in Neurosciences · doi:10.1016/0166-2236(90)90020-b · Cited by 91 · see citing works
Thanos, S., Kacza, J., Seeger, J., & Mey, J. (1994) · Trends in Neurosciences · doi:10.1016/0166-2236(94)90098-1 · Cited by 80 · see citing works
Involvement of Non‐Neuronal Cells in Entorhinal‐Hippocampal Reorganization Following Lesions
Bechmann, I., & Nitsch, R. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06727.x · Cited by 58 · see citing works
Self-citationMato, M., Ookawara, S., Mato, T. K., & Namiki, T. (1985) · American Journal of Anatomy · doi:10.1002/aja.1001720203 · Cited by 46 · see citing works
Kösel, S., Egensperger, R., Bise, K., Arbogast, S., Mehraein, P., & Graeber, M. B. (1997) · Acta Neuropathologica · doi:10.1007/s004010050747 · Cited by 43 · see citing works
Bechmann, I., & Nitsch, R. (1997) · Histochemistry and Cell Biology · doi:10.1007/s004180050125 · Cited by 35 · see citing works
Self-citationThe Cerebral Perivascular Cells
Angelov, D. N., Walther, M. R., Neiss, W. F., Streppel, M., & Guntinas‐Lichius, O. (1998) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-642-72251-6 · Cited by 31 · see citing works
Angelov, D. N., Walther, M., Neiss, W. F., Streppel, M., & Guntinas‐Lichius, O. (1998) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-642-72251-6_1 · Cited by 27 · see citing works
Blockade of AMPA receptors by nickel in cultured rat astrocytes
Telgkamp, P., Backus, K. H., & Deitmer, J. W. (1996) · Glia · doi:10.1002/(sici)1098-1136(199602)16:2 · Cited by 16 · see citing works
Über einige Lymphräume im Gehirne
Obersteiner, H. (1870) · Biodiversity Heritage Library (Smithsonian Institution) · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Microglia: Active sensor and versatile effector cells in the normal and pathologic brain
Hanisch, U.-K., & Kettenmann, H. (2007) · Nature Neuroscience · doi:10.1038/nn1997 · Cited by 3,676 · see citing works
Origin, fate and dynamics of macrophages at central nervous system interfaces
Goldmann, T., Wieghofer, P., Jordão, M. J. C., Prutek, F., Hagemeyer, N., Frenzel, K., Amann, L., Staszewski, O., Kierdorf, K., Krueger, M., et al. (2016) · Nature Immunology · doi:10.1038/ni.3423 · Cited by 1,209 · see citing works
Self-citationMrdjen, D., Pavlovic, A., Hartmann, F. J., Schreiner, B., Utz, S. G., Leung, B. P., Lelios, I., Heppner, F. L., Kipnis, J., Merkler, D., et al. (2018) · Immunity · doi:10.1016/j.immuni.2018.01.011 · Cited by 1,010 · see citing works
A new look at cerebrospinal fluid circulation
Brinker, T., Stopa, E., Morrison, J., & Klinge, P. (2014) · Fluids and Barriers of the CNS · doi:10.1186/2045-8118-11-10 · Cited by 819 · see citing works
Heterogeneity of CNS myeloid cells and their roles in neurodegeneration
Prinz, M., Priller, J., Sisodia, S. S., & Ransohoff, R. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2923 · Cited by 674 · see citing works
Kim, Y. S., & Joh, T. H. (2006) · Experimental & Molecular Medicine · doi:10.1038/emm.2006.40 · Cited by 655 · see citing works
What is the blood–brain barrier (not)?
Bechmann, I., Galea, I., & Perry, V. H. (2007) · Trends in Immunology · doi:10.1016/j.it.2006.11.007 · Cited by 520 · see citing works
Self-citationLymphatic drainage of the brain and the pathophysiology of neurological disease
Weller, R. O., Djuanda, E., Yow, H.-Y., & Carare, R. O. (2009) · Acta Neuropathologica · doi:10.1007/s00401-008-0457-0 · Cited by 488 · see citing works
Hawkes, C. A., & McLaurin, J. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0805453106 · Cited by 397 · see citing works
Macrophages at CNS interfaces: Ontogeny and function in health and disease
Kierdorf, K., Masuda, T., Jordão, M. J. C., & Prinz, M. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0201-x · Cited by 416 · see citing works
Schilling, M., Besselmann, M., Leonhard, C., Mueller, M., Ringelstein, E. B., & Kiefer, R. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00082-7 · Cited by 375 · see citing works
Macrophages: An Inflammatory Link Between Angiogenesis and Lymphangiogenesis
Corliss, B. A., Azimi, M. S., Munson, J. M., Peirce, S. M., & Murfee, W. L. (2016) · Microcirculation · doi:10.1111/micc.12259 · Cited by 356 · see citing works
Faraco, G., Sugiyama, Y., Lane, D., Garcia-Bonilla, L., Chang, H., Santisteban, M. M., Racchumi, G., Murphy, M., Van Rooijen, N., Anrather, J., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci86950 · Cited by 350 · see citing works
Dual Roles for Perivascular Macrophages in Immune-to-Brain Signaling
Serrats, J., Schiltz, J. C., García-Bueno, B., van Rooijen, N., Reyes, T. M., & Sawchenko, P. E. (2010) · Neuron · doi:10.1016/j.neuron.2009.11.032 · Cited by 253 · see citing works
Perivascular spaces—MRI marker of inflammatory activity in the brain?
Wuerfel, J., Haertle, M., Waiczies, H., Tysiak, E., Bechmann, I., Wernecke, K. D., Zipp, F., & Paul, F. (2008) · Brain · doi:10.1093/brain/awn171 · Cited by 244 · see citing works
Self-citationKim, W.-K., Alvarez, X., Fisher, J., Bronfin, B., Westmoreland, S., McLaurin, J., & Williams, K. (2006) · The American Journal of Pathology · doi:10.2353/ajpath.2006.050215 · Cited by 225 · see citing works
Groeschel, S., Chong, W. K., Surtees, R., & Hanefeld, F. (2006) · Neuroradiology · doi:10.1007/s00234-006-0112-1 · Cited by 230 · see citing works
Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function
Spiteri, A. G., Wishart, C. L., Pamphlett, R., Locatelli, G., & King, N. J. C. (2022) · Acta Neuropathologica · doi:10.1007/s00401-021-02384-2 · Cited by 216 · see citing works
“During homeostasis, circulating Ly6Chi monocytes traffic through semi-permeable CNS regions, such as the choroid plexus and dura mater, where they increase the local complexity of BAMs [128, 317].”
BackgroundInfluentialBrain perivascular macrophages: characterization and functional roles in health and disease
Faraco, G., Park, L., Anrather, J., & Iadecola, C. (2017) · Journal of Molecular Medicine · doi:10.1007/s00109-017-1573-x · Cited by 206 · see citing works
Bone-marrow-derived microglia: myth or reality?
Soulet, D., & Rivest, S. (2008) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2008.04.002 · Cited by 139 · see citing works
Martins-Ferreira, R., Calafell-Segura, J., Leal, B., Rodríguez-Ubreva, J., Martínez-Saez, E., Mereu, E., Pinho E Costa, P., Laguna, A., & Ballestar, E. (2025) · Nature Communications · doi:10.1038/s41467-025-56124-1 · Cited by 123 · see citing works
Maternal immune activation leads to activated inflammatory macrophages in offspring
Onore, C. E., Schwartzer, J. J., Careaga, M., Berman, R. F., & Ashwood, P. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.02.007 · Cited by 106 · see citing works
Fisher, Y., Nemirovsky, A., Baron, R., & Monsonego, A. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010830 · Cited by 83 · see citing works
Role of P2X7 Receptors in Immune Responses During Neurodegeneration
Oliveira-Giacomelli, Á., Petiz, L. L., Andrejew, R., Turrini, N., Silva, J. B., Sack, U., & Ulrich, H. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.662935 · Cited by 68 · see citing works
- Authors
- Bechmann, I., Kwidzinski, E., Kovac, A. D., Simbürger, E., Horvath, T., Gimsa, U., Dirnagl, U., Priller, J., & Nitsch, R.
- Affiliations
- Charité – Universitätsmedizin Berlin (DE)
- Corresponding author
- Bechmann, Ingo
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 168
- Issue
- 2
- Pages
- 242-249
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2108015661
- Cited by
- 134
- References
- 35
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 7 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 4 · 2012: 8
- FWCI
- 2.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- perivascular cells, macrophage turnover, monocyte/macrophage lineage, macrophage migration, blood-brain barrier, immune surveillance, bone marrow chimeras, phagocytosis, rat brain
- MeSH terms
- Animals, Basement Membrane, Brain, Cell Movement, Fluorescent Dyes, Macrophages, Oligodendroglia, Rats, Wistar, Rats
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