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.

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-a 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.Many surgical procedures involve the introduction of foreign bodies, such as catheters, stents and prostheses to the body. As the presence of foreign objects increases the risk of infections, much effort is made to minimize such complications by choosing the right surface material for this type of medical devices [1]. Silver ions have well-known antibacterial effects [2-4] making this metal an attractive coating material as it has been found to reduce the high risk of infections [5]. In medicine, silver coatings are used, e.g., on catheters for neurosurgery and vascular insertion [6,7] and on orthopaedic prostheses [8,9]. Different silver compounds are also used in dressings and foils for the treatment of infections in chronic ulcers and for improving the healing of burn wounds [10][11][12]. Outside the medical industry, silver coatings and nanosized silver particles are used in various housekeeping products, such as washing machines as well as incorporated into clothing, underwear and socks [13]. Nano-sized particles will be endocytosed or pinocytosed [14], and silver grains smaller than 10-15 lm will be readily phagocytosed [15,16], but the presence of a bigger silver surfa...

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