Biocompatibility of very small superparamagnetic iron oxide nanoparticles in murine organotypic hippocampal slice cultures and the role of microglia

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.

Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells

“…Hippocampal slice culture is widely used as a simplified, advantageous system in vitro for studying regeneration and neurodegeneration [ 27 ]. Organotypic hippocampal slice culture is similar to in vivo models, offering the possibility of analyzing neurogenesis and neuronal circuits, and is simpler compared to the neocortex [ 28 ]. In this study, we investigate the protective effect of quercetin on H 2 O 2 -induced apoptosis in PC-12 cells and organotypic hippocampal slice using TUNEL assay.…”

<p>Preparation and Evaluation of Recombinant Human Erythropoietin Loaded Tween 80-Albumin Nanoparticle for Traumatic Brain Injury Treatment</p>

“…In recent years, the biocompatibility of nanoparticles with microglia has been widely studied, amidst serving as a sensitive marker to evaluate the toxicity of exogenous toxicants. 38 , 39 The results indicated that rh-EPO-Tw-ABNPs had no toxicity on the brain and nerve cells.…”

Dynamic changes of inflammation and apoptosis in cerebral ischemia‑reperfusion injury in mice investigated by ferumoxytol‑enhanced magnetic resonance imaging

“…Microglia are important imaging targets for studying the inflammatory response after stroke ( 61 ). The region where USPIO aggregation causes signal changes on magnetic resonance images represents the activated microglia aggregation region ( 62 ). While ferumoxytol has a long half-life in blood, its half-life is only 45 min in mice, and previous studies have shown that almost no ferumoxytol is present in cerebral vessels 24 h after injection ( 63 ).…”