Cited by 254Barrier Structure and Function StudiesChemokine receptors and signalingAcute Ischemic Stroke Management

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Effects of the Chemokine CCL2 on Blood–Brain Barrier Permeability during Ischemia–Reperfusion Injury

Dimitrijevic, Oliver B, Stamatovic, Svetlana M, Keep, Richard F, Andjelkovic, Anuska V·2006·Journal of Cerebral Blood Flow & Metabolism

DOI 10.1038/sj.jcbfm.9600229

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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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Authors: Dimitrijevic, O. B., Stamatovic, S. M., Keep, R. F., & Andjelkovic, A. V.
Affiliations: University of Michigan (US)
Corresponding author: Andjelkovic, Anuska V
ORCID: Stamatovic, Svetlana M
Keep, Richard F
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
DOI: 10.1038/sj.jcbfm.9600229
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
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
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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Effects of the Chemokine CCL2 on Blood–Brain Barrier Permeability during Ischemia–Reperfusion Injury

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