Abstract: Superparamagnetic iron oxide nanoparticles (SPIO) are applied as
contrast media for magnetic resonance imaging (MRI) and treatment of
neurologic diseases despite the fact that important information concerning
their local interactions is still lacking. Due to their small size, SPIO have
great potential for magnetically labeling different cell populations,
facilitating their MRI tracking in vivo. Before SPIO are applied, however,
their effect on cell viability and tissue homoeostasis should be studied
thoroughly. We have previously published data showing how citrate-coated very
small superparamagnetic iron oxide particles (VSOP) affect primary microglia
and neuron cell cultures as well as neuron-glia cocultures. To extend our
knowledge of VSOP interactions on the three-dimensional multicellular level,
we further examined the influence of two types of coated VSOP (R1 and R2) on
murine organotypic hippocampal slice cultures. Our data show that 1) VSOP can
penetrate deep tissue layers, 2) long-term VSOP-R2 treatment alters cell
viability within the dentate gyrus, 3) during short-term incubation VSOP-R1
and VSOP-R2 comparably modify hippocampal cell viability, 4) VSOP treatment
does not affect cytokine homeostasis, 5) microglial depletion decreases VSOP
uptake, and 6) microglial depletion plus VSOP treatment increases hippocampal
cell death during short-term incubation. These results are in line with our
previous findings in cell coculture experiments regarding microglial
protection of neurite branching. Thus, we have not only clarified the
interaction between VSOP, slice culture, and microglia to a degree but also
demonstrated that our model is a promising approach for screening
nanoparticles to exclude potential cytotoxic effects