Metallic silver fragments cause massive tissue loss in the mouse brain.

Silver is a metal with well-known antibacterial effects. This makes silver an attractive coating material for medical devices for use inside the body, e.g. orthopaedic prostheses and catheters used in neurosurgery as it has been found to reduce the high risk of infections. Lately, the use of nano-silver particles in the industry, e.g. woven into fabrics and furniture has increased, and thus the exposure to silver particles in daily life increases. To study the effect of metallic silver particles on nervous tissue, we injected micron-sized silver particles into the mouse brain by stereotactic procedures. After 7, 14 days and 9 months, the silver-exposed animals had considerable brain damage seen as cavity formation and inflammation adjacent to the injected metallic silver particles. The tissue loss involved both cortical and hippocampal structures and resulted in enlargement of the lateral ventricles. Autometallographic silver enhancement showed silver uptake in lysosomes of glia cells and neurons in the ipsilateral cortex and hippocampus alongside a minor uptake on the contralateral side. Silver was also detected in ependymal cells and the choroid plexus. After 9 months, spreading of silver to the kidneys was seen. Cell counts of immunostained sections showed that metallic silver induced a statistically significant inflammatory response, i.e. increased microgliosis (7 days: p < 0.0001; 14 days: p < 0.01; 9 months: p < 0.0001) and TNF-α expression (7 and 14 days: p < 0.0001; 9 months: p = 0.91). Significant astrogliosis (7, 14 days and 9 months: p < 0.0001) and increased metallothionein (MT I + II) expression (7 and 14 days: p < 0.0001; 9 months: p < 0.001) were also seen in silver-exposed brain tissue. We conclude that metallic silver implants release silver ions causing neuroinflammation and a progressive tissue loss in the brain.

In vivo liberation of silver ions from metallic silver surfaces.

In vivo liberation of electrically charged silver atoms/silver ions from metallic silver pellets, silver grids and silver threads placed in the brain, skin and abdominal cavity was proved by way of the histochemical technique autometallography (AMG). A bio-film or "dissolution membrane" inserted between the metallic surface and macrophages was recognized on the surface of the implanted silver after a short period of time. Bio-released silver ions bound in silver-sulphur nanocrystals were traced within the first 24 h in the "dissolution membrane" and the "dissolucytotic" macrophages. In animals that had survived 10 days or more, silver nanocrystals were detected both extra- and intracellularly in places far away from the implant including regional lymph nodes, liver, kidneys and the central nervous system (CNS). The accumulated silver was always confined to lysosome-like organelles. Dissolucytotic silver was extracellularly related to collagen fibrils and fibres in connective tissue and basement membranes. Our study demonstrates that (1) the number of bio-released silver ions depends on the size of the surface of the implanted silver, (2) the spread of silver ions throughout the body takes place primarily not only through the vascular system, but also by retrograde axonal transport. It is concluded that implantation of silver or silver-plated devices is not recommendable.

Cultured macrophages cause dissolucytosis of metallic silver.

The present study proves that cultured macrophages can liberate silver ions from metallic silver surfaces by a process called dissolucytosis. Macrophages (J774) were grown on a silver plate for different periods of time and after fixation in glutaraldehyde, they were subjected to autometallograhy in order to amplify possible cellular silver-sulphur nanocrystals. Light and electron microscopic analysis of the cells revealed that silver ions released from the plate had been taken up by the macrophages and accumulated in lysosome-like structures. We found that the liberation of silver ions takes place extracellularly and is caused by chemical activity in a dissolution membrane, most likely secreted and organized by the macrophages. The liberation and the subsequent uptake of silver ions in the macrophages is a relatively fast process and the resulting silver-sulphur nanocrystals can be observed in macrophages that have been in contact with metallic silver for only a few minutes. Our findings indicate that the speed of dissolucytosis is highly influenced by the chemical nature of the object exposed to the dissolucytotic process which is likely to occur whenever macrophages encounter a non-phagocytosable foreign object.