The DOI matches its Crossref record; 54 of the 55 references it cites were found in a registry or an index.
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
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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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