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Effects of the Chemokine CCL2 on Blood–Brain Barrier Permeability during Ischemia–Reperfusion Injury
Abstract
The chemokine CCL2 is considered as one of the main effectors driving postischemic infiltration of monocytes into the brain parenchyma. New experimental data, however, suggest that CCL2 could also participate in blood–brain barrier (BBB) ‘opening’ during the transmigration of monocytes. The current study examines the role of CCL2 in regulating BBB permeability after ischemia in vitro. To address this issue, an in vitro BBB model (coculture of astrocytes and brain endothelial cells) was subjected to 5 h of oxygen glucose deprivation, followed by reoxgenation ( in vitro ischemia/reperfusion (I/R)) for 0 to 48 h. During reperfusion, there was a biphasic enhancement of barrier permeability, with a 200-fold increase in barrier permeability to FITC-albumin at 6 h and a further period of disruption around 24 h. The latter coincided with increased secretion of CCL2 by both astrocytes and brain endothelial cells and increased levels of the CCL2 receptor, CCR2. Applying antisense oligonucleotide or neutralizing antibody to block CCL2 significantly decreased I/R-induced enhancement of BBB permeability (approximately twofold) and redistribution of tight-junction (TJ) proteins (occludin, zonula occluden-1, 2, claudin-5). Similarly, absence of CCR2 from endothelial cells caused stabilization of TJ complexes and decreased the permeability of brain endothelial barrier during in vitro I/R. These data suggest CCL2/CCR2 has an important role in regulating brain endothelial permeability and might be a potential novel therapeutic target for stroke.
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“The CCL2-CCR2 chemotactic axis, in particular, is implicated in mediating leukocyte infiltration into the CNS under a variety of conditions including HIV encephalitis (Eugenin et al, 2006), ischemia (Dimitrijevic et al, 2006), prion disease (Gomez-Nicola et al, 2014), and stress (Wohleb et al, 2013).”
From Repeated Social Defeat, Neuroinflammation, and Behavior: Monocytes Carry the Signal (2017) · cites this paper as Dimitrijevic et al, 2006
In the citing paper
“the up-regulation of MCP-1 in the brain microenvironment during inflammatory response probably disrupts BBB integrity by redistribution of tight junction proteins, such as occludin and claudin-1, 5 and 11 and reorganization of the actin cytoskeleton in brain microvascular ECs (Stamatovic et al., 2003, 2005, 2006; Dimitrijevic et al., 2006).”
From The impact of microglial activation on blood-brain barrier in brain diseases (2014) · cites this paper as Dimitrijevic et al., 2006
Citations
Cites
Rollins, B. J. (1997) · Blood · doi:10.1182/blood.v90.3.909.909_909_928 · Cited by 2,126
The Molecular Biology of Leukocyte Chemoattractant Receptors
Murphy, P. M. (1994) · Annual Review of Immunology · doi:10.1146/annurev.iy.12.040194.003113 · Cited by 1,197
Inflammatory Mediators and Modulation of Blood–Brain Barrier Permeability
Abbott, N. J. (2000) · Cellular and Molecular Neurobiology · doi:10.1023/a:1007074420772 · Cited by 803
Molecular physiology and pathophysiology of tight junctions in the blood–brain barrier
Huber, J. D., Egleton, R. D., & Davis, T. P. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)02004-x · Cited by 790
Inflammatory Mechanisms after Ischemia and Stroke
Danton, G. H., & Dietrich, W. D. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.2.127 · Cited by 554
Fey, E. G., Wan, K. M., & Penman, S. (1984) · The Journal of Cell Biology · doi:10.1083/jcb.98.6.1973 · Cited by 542
Hallenbeck, J. M., Dutka, A. J., Tanishima, T., Kochanek, P. M., Kumaroo, K. K., Thompson, C. B., Obrenovitch, T. P., & Contreras, T. J. (1986) · Stroke · doi:10.1161/01.str.17.2.246 · Cited by 482
Blood-brain barrier biology and methodology
Pardridge, W. M. (1999) · Journal of NeuroVirology · doi:10.3109/13550289909021285 · Cited by 448
Okada, Y., Copeland, B. R., Mori, E., Tung, M. M., Thomas, W. S., & del Zoppo, G. J. (1994) · Stroke · doi:10.1161/01.str.25.1.202 · Cited by 435
Monocyte Chemoattractant Protein-1 Regulation of Blood–Brain Barrier Permeability
Stamatovic, S. M., Shakui, P., Keep, R. F., Moore, B. B., Kunkel, S. L., van Rooijen, N., & Andjelkovic, A. V. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600055 · Cited by 415
Self-citationCerebral microvascular changes in permeability and tight junctions induced by hypoxia-reoxygenation
Mark, K. S., & Davis, T. P. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00645.2001 · Cited by 408
Multiple Molecular Penumbras after Focal Cerebral Ischemia
Sharp, F. R., Lu, A., Tang, Y., & Millhorn, D. E. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200007000-00001 · Cited by 398
Stamatovic, S. M., Keep, R. F., Kunkel, S. L., & Andjelkovic, A. V. (2003) · Journal of Cell Science · doi:10.1242/jcs.00755 · Cited by 381
Self-citationBolton, S. J., Anthony, D. C., & Perry, V. H. (1998) · Neuroscience · doi:10.1016/s0306-4522(98)00058-x · Cited by 376
Kirk, J., Plumb, J., Mirakhur, M., & McQuaid, S. (2003) · The Journal of Pathology · doi:10.1002/path.1434 · Cited by 375
Kuroiwa, T., Ting, P., Martínez, H. R., & KLATZO, I. (1985) · Acta Neuropathologica · doi:10.1007/bf00688633 · Cited by 359
Gaillard, P. J., Voorwinden, L. H., Nielsen, J. L., Aa, I., Atsumi, R., Engman, H., Ringbom, C., de Boer, A. G., & Breimer, D. D. (2001) · European Journal of Pharmaceutical Sciences · doi:10.1016/s0928-0987(00)00123-8 · Cited by 332
Inflammatory Mediators of Cerebral Endothelium: A Role in Ischemic Brain Inflammation
Stanimirovic, D. B., & Satoh, K. (2000) · Brain Pathology · doi:10.1111/j.1750-3639.2000.tb00248.x · Cited by 311
Kim, J. S., Gautam, S., Chopp, M., Zaloga, C., Jones, M. L., Ward, P., & Welch, K. (1995) · Journal of Neuroimmunology · doi:10.1016/0165-5728(94)00138-e · Cited by 299
Peters, O., Back, T., Lindauer, U., Busch, C., Megow, D., Dreier, J. P., & Dirnagl, U. (1998) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199802000-00011 · Cited by 298
Monocyte Chemoattractant Protein-1 Deficiency is Protective in a Murine Stroke Model
Hughes, P., ALLEGRINI, P. R., Rudin, M., Perry, V. H., Mir, A. K., & Wießner, C. (2002) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200203000-00008 · Cited by 295
Burns, A. R., Walker, D. C., Brown, E. S., Thurmon, L. T., Bowden, R. A., Keese, C. R., Simon, S. I., Entman, M. L., & Smith, C. W. (1997) · The Journal of Immunology · doi:10.4049/jimmunol.159.6.2893 · Cited by 284
Stoll, G., Jander, S., & Schroeter, M. (2003) · Advances in experimental medicine and biology · doi:10.1007/978-1-4615-0123-7_3 · Cited by 281
IL-8 activates endothelial cell CXCR1 and CXCR2 through Rho and Rac signaling pathways
Schraufstätter, I. U., Chung, J., & Burger, M. (2001) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.2001.280.6.l1094 · Cited by 280
Chemokines and chemokine receptors in the CNS: a possible role in neuroinflammation and patterning
Mennicken, F., Maki, R. A., Souza, E. B. D., & Quirion, R. (1999) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(99)01308-5 · Cited by 277
Plumb, J., McQuaid, S., Mirakhur, M., & Kirk, J. (2002) · Brain Pathology · doi:10.1111/j.1750-3639.2002.tb00430.x · Cited by 274
The adhesion molecule ICAM-1 and its regulation in relation with the blood–brain barrier
Dietrich, J. (2002) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(02)00114-5 · Cited by 268
Neuroscience approached through cell culture
Pfeiffer, S. E. (1982) · CRC Press eBooks · Cited by 253
Blamire, A. M., Anthony, D. C., Rajagopalan, B., Sibson, N. R., Perry, V. H., & Styles, P. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-21-08153.2000 · Cited by 249
Molecular and cellular permeability control at the blood-brain barrier
Gloor, S. M., Wachtel, M., Bolliger, M. F., Ishihara, H., Landmann, R., & Frei, K. (2001) · Brain Research Reviews · doi:10.1016/s0165-0173(01)00102-3 · Cited by 244
Cytokines and adhesion molecules in stroke and related diseases
Kim, J. S. (1996) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(95)00338-3 · Cited by 214
Monocyte chemoattractant protein-1 messenger RNA expression in rat ischemic cortex.
Wang, X.-K., Yue, T., Barone, F., & Feuerstein, G. (1995) · Stroke · doi:10.1161/01.str.26.4.661 · Cited by 203
Monocyte chemoattractant protein-1 expressed in neurons and astrocytes during focal ischemia in mice
Che, X., Ye, W., Panga, L., Wu, D.-C., & Yang, G. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02328-9 · Cited by 201
Analysis of tight junctions during neutrophil transendothelial migration
Burns, A. R., Bowden, R. A., MacDonell, S. D., Walker, D. C., Odebunmi, T., Donnachie, E., Simon, S. I., Entman, M. L., & Smith, C. W. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.1.45 · Cited by 194
Novel lymphocyte-specific CC chemokines and their receptors
Yoshie, O., Imai, T., & Nomiyama, H. (1997) · Journal of Leukocyte Biology · doi:10.1002/jlb.62.5.634 · Cited by 193
Tsukamoto, T., & Nigám, S. K. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.26.16133 · Cited by 191
Bell, M. D., Taub, D. D., & Perry, V. H. (1996) · Neuroscience · doi:10.1016/0306-4522(96)00083-8 · Cited by 178
Matsumoto, T., Ikeda, K., Mukaida, N., Harada, A., Matsumoto, Y., Yamashita, J., & Matsushima, K. (1997) · PubMed · Cited by 154
Combination of Hypoxia/Aglycemia Compromises In Vitro Blood-Brain Barrier Integrity
Abbruscato, T. J., & Davis, T. P. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)38186-8 · Cited by 143
Paul, R. (2003) · Brain · doi:10.1093/brain/awg171 · Cited by 134
Elements of cerebral microvascular ischaemia
Petty, M. A., & Wettstein, J. G. (2001) · Brain Research Reviews · doi:10.1016/s0165-0173(01)00062-5 · Cited by 132
Losy, J., & Zaremba, J. (2001) · Stroke · doi:10.1161/hs1101.097380 · Cited by 130
Kastrup, A., Engelhorn, T., Beaulieu, C., de Crespigny, A. J., & Moseley, M. E. (1999) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(99)00121-5 · Cited by 96
Nitric oxide protects blood‐brain barrier in vitro from hypoxia/reoxygenation‐mediated injury
Utepbergenov, D., Mertsch, K., Sporbert, A., Tenz, K., Paul, M., Haseloff, R. F., & Blasig, I. E. (1998) · FEBS Letters · doi:10.1016/s0014-5793(98)00173-2 · Cited by 91
Kondo, T., Kinouchi, H., 川瀬, 誠., & Yoshimoto, T. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12555-6 · Cited by 70
Anin vitro model for endothelial permeability: Assessment of monolayer integrity
Kazakoff, P. W., McGuire, T. R., Hoie, E. B., Cano, M., & Iversen, P. L. (1995) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/bf02634568 · Cited by 49
Yang, G., Mao, Y. Q., Zhou, L.-F., Ye, W., Liu, X.-H., Gong, C., & Betz, A. L. (1999) · Molecular Brain Research · doi:10.1016/s0169-328x(99)00205-3 · Cited by 48
Leech giant glial cell: functional role in a simple nervous system
Deitmer, J. W., Rose, C. R., Munsch, T., Schmidt, J., Nett, W., Schneider, H.-P., & Lohr, C. (1999) · Glia · doi:10.1002/(sici)1098-1136(199912)28:3 · Cited by 43
Self-citationInfiltration of inflammatory cells through brain endothelium.
Couraud, P.-O. (1998) · PubMed · Cited by 40
Morphological changes in acute cerebral ischemia after occlusion and reperfusion in the rat.
Nakagawa, Y., Fujimoto, N., Matsumoto, K., & Cervós-Navarro, J. (1990) · PubMed · Cited by 35
Lindauer, U., Dreier, J. P., Angstwurm, K., Rubin, I., Villringer, A., Einhäupl, K. M., & Dirnagl, U. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199611000-00008 · Cited by 32
Muruganandam, A., Smith, C., Ball, R., Herring, T., & Stanimirovic, D. B. (2000) · Acta neurochirurgica. Supplementum · doi:10.1007/978-3-7091-6346-7_6 · Cited by 19
Schürer, L., Corvin, S., Röhrich, F., Abels, C., & Baethmann, A. J. (1994) · Springer eBooks · doi:10.1007/978-3-7091-9334-1_13 · Cited by 6
Collins (1998) · doi:10.1002/(sici)1097-4652(199807)176:1
Research works printed but not linked: 10
- Abbruscato TJ, 1999, J Pharmacol Exp Ther, 289, 668
- Couraud PO, 1998, Pathol Biol (Paris), 46, 176
- Dirnagl U, 1999, TINS, 22, 391
- Huber JD, 2001, TINS, 24, 719
- Matsumoto T, 1997, Lab Invest, 77, 119
- Menicken F, 1999, TIPS, 20, 73
- Nakagawa Y, 1990, Adv Neurol, 52, 21
- 10.1182/blood.V90.3.909 · DOI
- Schuerer L, 1994, Acta Neurochir Suppl, 60, 51
- Stoll G, 2002, Adv Exp Med Biol, 513, 87
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Sandoval, K. E., & WITT, K. A. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.08.005 · Cited by 984
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Metadata
- Authors
- Dimitrijevic, O. B., Stamatovic, S. M., Keep, R. F., & Andjelkovic, A. V.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Andjelkovic, Anuska V
- Venue
- Journal of Cerebral Blood Flow & Metabolism
- Publisher
- SAGE Publications
- Published
- 2006-06
- Volume
- 26
- Issue
- 6
- Pages
- 797-810
- ISSN
- 0271-678X (ISSN-L)
- 1559-7016
- OpenAlex
- W1995446848
- Cited by
- 252
- References
- 55
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 26 · 2023: 18 · 2022: 19 · 2021: 10 · 2020: 12 · 2019: 9 · 2018: 16 · 2017: 13 · 2016: 11 · 2015: 9 · 2014: 16 · 2013: 16 · 2012: 11
- FWCI
- 2.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Cerebral Blood Flow & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Michigan
- National Institute of Neurological Disorders and Stroke (R01NS044907, NS-044907)
- Division of Chemistry
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Chemokine receptors and signaling
- Health Sciences › Medicine › Clinical Neurology › Acute Ischemic Stroke Management
- Keywords
- MCP-1, CCR2, blood-brain barrier permeability, ischemia-reperfusion injury, monocyte transmigration, tight junction proteins, occludin, claudin-5, zonula occludens-1, brain endothelial cells, astrocytes, oxygen-glucose deprivation, stroke, chemokines
- MeSH terms
- Animals, Astrocytes, Blood-Brain Barrier, Capillary Permeability, Cell Movement, Cells, Cultured, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Blotting, Western, Reperfusion Injury, Electric Impedance, Coculture Techniques, Chemokine CCL2, Receptors, Chemokine, Reverse Transcriptase Polymerase Chain Reaction, Endothelial Cells, Mice, Receptors, CCR2
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