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66th Annual Meeting of the German Society of Neurosurgery (DGNC)
Friendship Meeting with the Italian Society of Neurosurgery (SINch)

German Society of Neurosurgery (DGNC)

7 - 10 June 2015, Karlsruhe

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Chemokine secretion of murine neuronglia co-cultures influences neuronal vitality and neurite branching after exposure to superparamagnetic iron oxide nanoparticles

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  • Jana Glumm - Klinik für Neurochirurgie, HELIOS Klinikum Berlin-Buch, Deutschland; Institute für Zell - und Neurobiologie, Charité - Universitätsmedizin Berlin
  • Jenni Neubert - Institute für Zell - und Neurobiologie, Charité - Universitätsmedizin Berlin
  • Susanne Wagner - Institute für Radiology, Charité - Universitätsmedizin Berlin
  • Anja Bräuer - Institute für Zell - und Neurobiologie, Charité - Universitätsmedizin Berlin
  • Jürgen Kiwit - Klinik für Neurochirurgie, HELIOS Klinikum Berlin-Buch, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 66. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC). Karlsruhe, 07.-10.06.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. DocP 026

doi: 10.3205/15dgnc424, urn:nbn:de:0183-15dgnc4247

Published: June 2, 2015

© 2015 Glumm et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Objective: The potential use of nanometer-sized superparamagnetic iron oxide particles (SPIOs) as MRI contrast agents in medical diagnostics is continuously increasing. SPIOs are being investigated for imaging the pathogenesis of several CNS diseases in vivo. We have shown before, that SPIO accumulation induces decreased microglial survival and that neurite branching increases in a SPIO-type and dose-dependent manner. Accordingly, we now studied the interaction of those particles within a murine neuron glia cocultures and changes in the chemokine secretion profile.

Method: Microglia and astrocytes from C57Bl6/J pups (P0-P2) and hippocampal neurons from mice embryos (E18) were cultured separately and in a co-culture. Very Small Iron Oxide Particles (VSOP-R1/-R2), differing in size or the clinically proven polymer-coated Resovist® (Bayer Schering Pharma AG) or Feraheme® (AMAG Pharmaceuticals, Inc.), were added at 0,5mM for 24 hours. We analyzed arrays to identify up- und down regulated cytokines and chemokines. We performed Western blot analysis to identify proteins and factors that mediate SPIO actions to investigate the underlying signaling pathways. We localized SPIOs and evaluated the degree of cellular uptake and extracellular binding with transmission electron microscopy.

Results: We observed differences within the applied SPIOs. For example we found upregulation for G-CSF, IL-1ra, CXCL10 and CXCL2/MIP-2 after microglia treatment with Resovist and downregulation of CXCL10, CCL2/MCP-1 and TIMP-1 after neuron treatment. In contrast the co-culture CD54/sICAM-1, CCL12/MCP-5 and CXCL2/MIP-2 where down regulated. Transmission electron microscopy showed great amount of intracellular uptake for all SPIOs in microglia except for Feraheme.

Conclusions: VSOPs, Resovist® and Feraheme® have so far not been reviewed in terms of interactions with CNS tissue and potential adverse effects. Our experiments show, that there are considerable interferences between primary murine CNS cells and applied IONPs as well as differences for the evaluated SPIOs. The analysis of particle interactions and subsequent effects substantially contribute to the assessment of chances and limits in applications of SPIOs for diagnostics (e.g. MRI) in humans.