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Stroke. 2009 Apr;40(4):1458-66. doi: 10.1161/STROKEAHA.108.535930. Epub 2009 Feb 26.

Mechanisms of C-reactive protein-induced blood-brain barrier disruption.

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  • 1Institute of Physiology and Pathophysiology, Johannes Gutenberg University of Mainz, Mainz, Germany. luhmann@uni-mainz.de



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.


We used a cell coculture model of the blood-brain barrier and the guinea pig isolated whole brain preparation.


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.


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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