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Archives of Toxicology

, Volume 86, Issue 7, pp 1099–1105 | Cite as

In vivo visualisation of nanoparticle entry into central nervous system tissue

  • Petra Henrich-NoackEmail author
  • Sylvia Prilloff
  • Nadine Voigt
  • Jing Jin
  • Werner Hintz
  • Jürgen Tomas
  • Bernhard A. Sabel
Inorganic compounds

Abstract

Because the potential neurotoxicity of nanoparticles is a significant issue, characterisation of nanoparticle entry into the brain is essential. Here, we describe an in vivo confocal neuroimaging method (ICON) of visualising the entry of fluorescent particles into the parenchyma of the central nervous system (CNS) in live animals using the retina as a model. Rats received intravenous injections of fluorescence-labelled polybutyl cyanoacrylate nanoparticles that had been synthesised by a standard miniemulsion polymerisation process. We performed live recording with ICON from before and up to 9 days after particle injection and took photomicrographs of the retina. In addition, selective retrograde labelling of the retinal ganglion cells was achieved by stereotaxic injection of a fluorescent dye into the superior colliculus. Using ICON, we observed vascular kinetics of nanoparticles (wash-in within seconds), their passage to the retina parenchyma (within minutes) and their distribution (mainly cellular) under in vivo conditions. For the detection of cell loss—which is important for the evaluation of toxic effects—in another experiment, we semi-quantitatively analysed the selectively labelled retinal neurons. Our results suggest that the dye per se does not lead to neuronal death. With ICON, it is possible to study nanoparticle kinetics in the retina as a model of the blood-brain barrier. Imaging data can be acquired within seconds after the injection, and the long-term fate of cellular uptake can be followed for many days to study the cellular/extracellular distribution of the nanoparticles. ICON is thus an effective and meaningful tool to investigate nanoparticle/CNS interactions.

Keywords

Polybutyl cyanoacrylate nanoparticles Blood-brain barrier Blood-retina barrier In vivo confocal neuroimaging Brain 

Notes

Conflict of interest

We have no conflict of interest.

Supplementary material

Supplementary material 1 (AVI 21646 kb)

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Petra Henrich-Noack
    • 1
    Email author
  • Sylvia Prilloff
    • 1
  • Nadine Voigt
    • 1
  • Jing Jin
    • 2
  • Werner Hintz
    • 2
  • Jürgen Tomas
    • 2
  • Bernhard A. Sabel
    • 1
  1. 1.Institute of Medical PsychologyOtto-von-Guericke UniversityMagdeburgGermany
  2. 2.Institute of Mechanical Process EngineeringOtto-von-Guericke UniversityMagdeburgGermany

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