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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 μm 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.

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Acknowledgments

The authors are grateful for the skillful technical assistance of Magdalena Maria Kus, Dorete Jensen, Albert Meier, Majken Sand and Karin Wiedemann. We gratefully acknowledge the financial support from the following foundations: IMK Almene Fond, Aase and Ejnar Danielsens Fond, Hede Nielsen Fonden, Fonden til Lægevidenskabens Fremme, Eva & Henry Frænkels Mindefond, Dir. Leo Nielsens Legat, Kathrine og Vigo Skovgaards Fond, Th. Maigaard’s Eftf. Fru Lily Benthine Lunds Fond af 1/6 1978, and the Aarhus University Research Foundation.

Conflicts of interest

Professor Danscher owns a small company, Berlock ApS, supported by government money that have patented the use of heavy metals as a dispenser of metal ions: European Patent: EP 1 395 268 (issued on January 19, 2005)based on the article “In vivo liberation of gold ions from gold implants. Histochem Cell Biol (2002) 117:447–452. The present study has been carried out at the two university laboratories (University of Aarhus and University of Copenhagen, Denmark) named in the article and the company has not been involved in the work in any way.

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Correspondence to Agnete Larsen.

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G. Danscher, M. Penkowa and M. Stoltenberg have contributed equally to the content of this manuscript.

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Larsen, A., Kolind, K., Pedersen, D.S. et al. Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury. Histochem Cell Biol 130, 681–692 (2008). https://doi.org/10.1007/s00418-008-0448-1

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  • DOI: https://doi.org/10.1007/s00418-008-0448-1

Keywords

  • Apoptosis
  • Autometallography (AMG)
  • Dissolucytosis
  • Gold
  • Immunosuppression
  • Microglia
  • Neuroregeneration
  • Stem cells