title: Metallic silver fragments cause massive tissue loss in the mouse brain.
abstract: 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.
authors.affiliation: Section of Neurobiology, Department of Anatomy, Aarhus University, Aarhus, Denmark. lloc@ana.au.dk
authors.forename: Linda Jansons
authors.initials: LJ
authors.lastname: Locht
authors.forename: Mie Ø
authors.initials: MØ
authors.lastname: Pedersen
authors.forename: Sara
authors.initials: S
authors.lastname: Markholt
authors.forename: Bo Martin
authors.initials: BM
authors.lastname: Bibby
authors.forename: Agnete
authors.initials: A
authors.lastname: Larsen
authors.forename: Milena
authors.initials: M
authors.lastname: Penkowa
authors.forename: Meredin
authors.initials: M
authors.lastname: Stoltenberg
authors.forename: Jørgen
authors.initials: J
authors.lastname: Rungby
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D002452:Cell Count; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D008668:Metallothionein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D019736:Prostheses and Implants; D012834:Silver / Q000493:pharmacokinetics / Q000633:toxicity*; D013238:Stereotaxic Techniques; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D012834:Silver; D008668:Metallothionein