Mechanisms of C-Reactive Protein-Induced Blood–Brain Barrier Disruption
Abstract
BACKGROUND AND PURPOSE: Increased mortality after stroke is associated with brain edema formation and high plasma levels of the acute phase reactant C-reactive protein (CRP). The aim of this study was to examine whether CRP directly affects blood-brain barrier stability and to analyze the underlying signaling pathways. METHODS: We used a cell coculture model of the blood-brain barrier and the guinea pig isolated whole brain preparation. RESULTS: We could show that CRP at clinically relevant concentrations (10 to 20 microg/mL) causes a disruption of the blood-brain barrier in both approaches. The results of our study further demonstrate CRP-induced activation of surface Fcgamma receptors CD16/32 followed by p38-mitogen-activated protein kinase-dependent reactive oxygen species formation by the NAD(P)H-oxidase. The resulting oxidative stress increased myosin light chain kinase activity leading to an activation of the contractile machinery. Blocking myosin light chain phosphorylation prevented the CRP-induced blood-brain barrier breakdown and the disruption of tight junctions. CONCLUSIONS: Our data identify a previously unrecognized mechanism linking CRP and brain edema formation and present a signaling pathway that offers new sites of therapeutic intervention.
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CRP appears to determine blood-brain barrier disruption through binding with some ligands (Fc gamma receptors, CD16, CD32) expressed in microglia, astrocytes, and endothelial cells.
“In addition, CRP appears to determine BBB disruption, through the binding with some ligands (i.e., Fc gamma receptors, CD16, CD32), expressed in the microglia, astrocytes, and endothelial cells [39].”
From C-Reactive protein as a biomarker for major depressive disorder? (2022) · cites this paper as [39]
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- Authors
- Kuhlmann, C. R. W., Librizzi, L., Closhen, D., Pflanzner, T., Lessmann, V., Pietrzik, C. U., de Curtis, M., & Luhmann, H. J.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- From the Institute of Physiology and Pathophysiology (C.R.W.K., D.C., V.L., H.J.L.), Johannes Gutenberg University of Mainz, Mainz, Germany; the Department of Experimental Neurophysiology (L.L., M.d.C.), Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta via Celoria 11, Milan, Italy; the Institute for Physiological Chemistry and Pathobiochemistry (T.P., C.U.P.), Johannes Gutenberg University of Mainz, Mainz, Germany; and the Institute for Physiology (V.L.), Otto-von-Guericke University,...
- Venue
- Stroke
- Published
- 2009-04
- Volume
- 40
- Issue
- 4
- Pages
- 1458-1466
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- OpenAlex
- W2117589588
- Cited by
- 138
- References
- 47
- Citations by year
- 2026: 8 · 2025: 21 · 2024: 9 · 2023: 11 · 2022: 10 · 2021: 11 · 2020: 7 · 2019: 9 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 8 · 2014: 3 · 2013: 4 · 2012: 9
- FWCI
- 4.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Stroke (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
- Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
- Keywords
- C-reactive protein, blood-brain barrier disruption, cerebral edema, p38 MAPK, NADPH oxidase, reactive oxygen species, myosin light chain kinase, tight junctions, oxidative stress, acute phase proteins
- MeSH terms
- Animals, Blood-Brain Barrier, Brain Edema, C-Reactive Protein, Cells, Cultured, Endothelium, Vascular, Guinea Pigs, Phosphorylation, Signal Transduction, Reactive Oxygen Species, Receptors, IgG, Coculture Techniques, Myosin Light Chains, Tight Junctions, Stroke, p38 Mitogen-Activated Protein Kinases, Rats
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