Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury.
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.
Larsen
Agnete
A
Department of Neurobiology, Institute of Anatomy, University of Aarhus, 8000 Aarhus C, Denmark. al@neuro.au.dk
Kolind
Kristian
K
Pedersen
Dan Sonne
DS
Doering
Peter
P
Pedersen
Mie Ostergaard
MO
Danscher
Gorm
G
Penkowa
Milena
M
Stoltenberg
Meredin
M
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001930:Brain Injuries / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D006046:Gold / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007249:Inflammation / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D009416:Nerve Regeneration / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D010316:Particle Size; D013499:Surface Properties
D000893:Anti-Inflammatory Agents; D006046:Gold