Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury

Abstract

Traumatic brain injury results in loss of neurons caused as much by the resulting neuroinflammation as by the injury. Gold salts are known to be immunosuppressive, but their use are limited by nephrotoxicity. However, as we have proven that implants of pure metallic gold release gold ions which do not spread in the body, but are taken up by cells near the implant, we hypothesize that metallic gold could reduce local neuroinflammation in a safe way. Bio-liberation, or dissolucytosis, of gold ions from metallic gold surfaces requires the presence of disolycytes i.e. macrophages and the process is limited by their number and activity. We injected 20-45 mum gold particles into the neocortex of mice before generating a cryo-injury. Comparing gold-treated and untreated cryolesions, the release of gold reduced microgliosis and neuronal apoptosis accompanied by a transient astrogliosis and an increased neural stem cell response. We conclude that bio-liberated gold ions possess pronounced anti-inflammatory and neuron-protective capacities in the brain and suggest that metallic gold has clinical potentials. Intra-cerebral application of metallic gold as a pharmaceutical source of gold ions represents a completely new medical concept that bypasses the blood-brain-barrier and allows direct drug delivery to inflamed brain tissue.

Effects of dissolucytotic gold ions on recovering brain lesions

“…This uptake of gold in the lysosomal compartment after exposure to metallic gold implants or gold particles has been confirmed in tissues from rats and mice (Danscher 2002;Larsen et al 2007Larsen et al , 2008. In the brain, gold ions released from a metallic depot, e.g.…”

“…Auromedication in the brain of mice with cryo-lesions has ignited a hope of finding ways of suppressing inflammation in the brain (Larsen et al 2008;Pedersen et al 2009a, b). By inserting a local depot of metallic gold, that can be made removable, in an area of the brain prone to inflammation it might be possible, in a safe way, to secure a control of the immunological processes in that particular area as long as it is found needed.…”

State-of-the-art technologies, current opinions and developments, and novel findings: news from the field of histochemistry and cell biology

“…Gold salts are known to be immunosuppressive, possibly by altering the functions of macrophages by inhibiting their lysosomes and lowering their production of proinXammatory cytokines (see Larsen et al 2008). It has previously been shown in vitro that gold ions are released from metallic gold implants by macrophages grown on metallic gold surfaces (Larsen et al 2007), a process which has been termed dissolucytosis and which prevents toxic side eVects of gold since it is a very slow process resulting in a liberation of gold taken up solely by cells close to the implants.…”

“…It has previously been shown in vitro that gold ions are released from metallic gold implants by macrophages grown on metallic gold surfaces (Larsen et al 2007), a process which has been termed dissolucytosis and which prevents toxic side eVects of gold since it is a very slow process resulting in a liberation of gold taken up solely by cells close to the implants. Larsen et al (2008) now studied whether gold released from injected metallic gold particles could reduce local neuroinXammation caused by a focal cryo-lesion in mouse neocortex performed after injection of the gold particles. Using autometallography in tissue as well as histochemistry, immunohistochemistry, TUNEL-labelling, and quantitative methods, the authors succeeded in showing that gold was accumulated in both glia cells and neurons near the gold deposits in the lesioned area, and that, in comparison to non-treated cryolesions, gold treated ones displayed less microgliosis and neuronal apoptosis accompanied by a transient astrogliosis and increased neural stem cell response.…”

Ecological Risk Assessment of Arsenic and Metals in Surface Sediments from Estuarine and Coastal Areas of the Southern Bohai Sea, China

“…[9][10][11]26 Recently, bioreleased ionic Au from AuNPs was observed in mice. 27 Therefore, knowledge about the intertransformation of ionic Au species and AuNPs, is important for elucidating the environmental fate and behavior of engineered AuNPs.…”