gms | German Medical Science

Objective: The exposure to nanosized materials steadily grows due to an increasing number of nanoparticle applications in science and industry. Recent data indicate that silver nanoparticles may induce various inflammatory processes with a consecutive disruption of the blood-brain barrier. Therefore, the aim of the present in vivo study was to analyze, how circulating silver nanoparticles affect the interaction of leukocytes with the endothelium of the brain microvasculature.

Method: A cranial window chamber was prepared in 48 balb/c mice. In the first part 8 animals per group received 100 microlitre PBS (control), 2.5 mg/kg of 20 nm-sized silver nanoparticles (dissolved in 100 microlitre PBS) or 2.5 mg/kg of 100 nm-sized silver nanoparticles (dissolved in 100 microlitre PBS) via a carotid catheter. Subsequently, intravital fluorescence microscopy of the pial vessels was performed at 15 minutes and 6 hours after application for the analysis of microhemodynamics and leukocyte-endothelial cell interaction. The second part analysed the effects of PBS, 20 nm-sized silver nanoparticles and 100 nm-sized silver nanoparticles (n = 8) after 24 hours.

Results: In all groups, animals initially presented with comparable low numbers of adherent leukocytes (0 - 8 cells/mm²) in postcapillary pial venules at 15 min. However, application of silver nanoparticles resulted in an increased leukocyte-endothelial cell interaction over time, as indicated by elevated numbers of adherent leukocytes (20 nm-sized silver nanoparticles: 114±34 cells/mm²; 100 nm-sized 180±38 cells/mm²; p<0.05) after 6h when compared to controls (65±17 cells/mm²). After 24 hours the inflammatory effects were even more intensified (adherent leukocytes in control: 29±9 cells/mm²; 20 nm-sized silver nanoparticles: 162±45 cells/mm²; 100 nm-sized: 217±67 cells/mm²; p<0.05). All groups showed constant microhemodynamic parameters without differences between the groups. The PCR analysis showed a increase of the inflammatory protein ICAM gen expression after silver nanoparticles application.

Conclusions: The present study demonstrates that circulating silver nanoparticles promote the interaction of leukocytes with the endothelium of the brain microvasculature. This observation indicates that silver nanoparticles are capable of inducing an acute leukocytic inflammatory response in the brain, which may represent an essential pathophysiological step in the disruption of the blood brain barrier.