Abstract
Iron oxide nanoparticles (IONPs) are used for diverse medical approaches, although the potential health risks, for example adverse effects on brain functions, are not fully clarified. Several in vitro studies demonstrated that the different types of brain cells are able to accumulate IONPs and reported a toxic potential for IONPs, at least for microglia. However, little information is available for the in vivo effects of direct application of IONPs into the brain over time. Therefore, we examined the cellular responses and the distribution of iron in the rat brain at different time points after local infusion of IONPs into selected brain areas. Dispersed IONPs or an equivalent amount of low molecular weight iron complex ferric ammonium citrate or vehicle were infused into the medial prefrontal cortex (mPFC), the caudate putamen (CPu), or the dorsal hippocampus (dHip). Rats were sacrificed 1 day, 1 week, or 4 weeks post-infusion and brain sections were histologically examined for treatment effects on astrocytes, microglia, and neurons. Glial scar formation was observed in the mPFC and CPu 1 week post-infusion independent of the substance and probably resulted from the infusion procedure. Compared to vehicle, IONPs did not cause any obvious additional adverse effects and no additional tissue damage, while the infusion of ferric ammonium citrate enhanced neurodegeneration in the mPFC. Results of iron staining indicate that IONPs were mainly accumulated in microglia. Our results demonstrate that local infusions of IONPs in selected brain areas do not cause any additional adverse effects or neurodegeneration compared to vehicle.
Highlights
During the last decade, iron oxide nanoparticles (IONPs) became increasingly useful for biomedical applications because of their biocompatibility, magnetic properties, and stability (Xie et al 2018)
Since the understanding of the fate of IONPs in the brain is still incomplete, the present study investigated the distribution of IONPs and possible tissue lesions at different time points after local infusion into three different brain areas compared with appropriate control infusions
Bishop and Robinson (2001) already demonstrated a high vulnerability of cortical neurons to mechanical impact as a result of a surgical intervention indicated by high number of Fluorojade C (FJC) + cells around the injection tract
Summary
Iron oxide nanoparticles (IONPs) became increasingly useful for biomedical applications because of their biocompatibility, magnetic properties, and stability (Xie et al 2018). Intranasal instillation of IONPs. Neurotoxicity Research has been reported to increase the number of activated microglia in olfactory bulb, striatum and hippocampus (Wang et al 2011a, b; Wu et al 2013) and to cause oxidative stress in hippocampus, olfactory bulb and cerebellum (Wang et al 2009) leading to neurodegeneration in the CA3 region of the hippocampus (Wang et al 2007). After systemic application, IONP accumulation, elevated NO levels, increased acetylcholinesterase activity, lactate dehydrogenase leakage, and demyelination were detected (Dhakshinamoorthy et al 2017). These studies indicate the importance of further investigating the toxic potential of IONPs on brain cells in vivo as well as the ability of the brain to recover from IONP-induced neurodegeneration
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