Metallic gold treatment reduces proliferation of inflammatory cells, increases expression of VEGF and FGF, and stimulates cell proliferation in the subventricular zone following experimental traumatic brain injury
Mie Østergaard Pedersen1, Agnete Larsen2, Dan Sonne Pedersen1, Meredin Stoltenberg2* and Milena Penkowa1*
1Section of Neuroprotection, Department of Neuroscience and Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark and 2Neurobiology, Institute of Anatomy, University of Aarhus, Aarhus, Denmark
*These authors contributed equally to the work.
Offprint requests to: Mie Østergaard Pedersen, Section of Neuroprotection, Panum Institute, University of Copenhagen, Blegdamsvej 3, building 18.1.45, DK-2200 Copenhagen N, Denmark. e-mail: firstname.lastname@example.org
Summary. Traumatic brain injury represents a leading cause of morbidity in young individuals and there is an imperative need for neuroprotective treatments limiting the neurologic impairment following such injury. It has recently been demonstrated that bio-liberated gold ions liberated from small metallic gold implants reduce inflammation and neuronal apoptosis, while generating an increased neuronal stem cell response following focal brain damage. In this study mice were subjected to a unilateral traumatic cryo-lesion with concomitant injection of 25-45 µm gold particles near the lesion. Placebo-treated mice subjected to cryo-lesion served as controls. The effects of gold-treatment were investigated by examining gold-induced growth factor expression (VEGF and FGF) in the first two weeks after the insult, and the extent of the neurostimulatory effect of gold was explored by comparing cell proliferation in the subventricular zone as judged by immunohistochemical staining for CDC47. Vimentin staining revealed a decrease in activated microglia and a transient astrogliosis in response to the gold liberation. Moreover, gold ions significantly increase the expression of VEGF and FGF following trauma and a significant increase in cell proliferation in both the ipsilateral and the contralateral subventricular zone was found in response to gold-treatment. In conclusion: we confirmed the previously demonstrated anti-inflammatory effect of bio-liberated gold ions, and further show that metallic gold increases growth factor expression and adult neurogenesis. Histol Histopathol 24, 573-586 (2009)
Key words: Dissolucytosis, Growth factor, Metallic gold, Regeneration, Traumatic brain injury