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 μg/mL) causes a disruption of the blood-brain barrier in both approaches. The results of our study further demonstrate CRP-induced activation of surface Fcγ 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.
Original language | English |
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Pages (from-to) | 1458-1466 |
Number of pages | 9 |
Journal | Stroke |
Volume | 40 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 1 2009 |
Keywords
- Blood-brain barrier
- Edema
- Myosin light chain
- Stroke
ASJC Scopus subject areas
- Medicine(all)
- Cardiology and Cardiovascular Medicine
- Clinical Neurology
- Advanced and Specialised Nursing