Olfactory transport efficiency of the amorphous and crystalline manganese oxide nanoparticles

Romashchenko, A. V.; Petrovskii, D. V.; Sharapova, M. B.; Moshkin, Yuri M.; Купер, К. Э.; Morozova, Ksenia N.; Киселева, Елена; Мошкин, М. П.

doi:10.18699/vj17.305

Cited by 1 publication

(6 citation statements)

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“…As shown in our previous work, relaxation values (R1, ms -1 , see Fig. 1, c) of Mn 3 O 4 -NPs correlate with manganese concentration in the samples (Romashchenko et al, 2017). In vivo experiments showed that the amplitude of the MRI signal in OB 12 hours after the intranasal application of Mn 3 O 4 -NPs was directly proportional to the manganese concentration in the tissue (Romashchenko et al, 2017).…”

Section: Methodssupporting

confidence: 74%

“…OB were taken for calibration, since the concentration of nanoparticles after the intranasal or inhalation administration is the highest in this region (Moshkin et al, 2014). Earlier, we demonstrated low solubility of Mn 3 O 4 -NPs at different pH (4-7), which entitled us to regard the observed changes in the MRI signal in mouse brain divisions after intranasal/intravenous administration of Mn 3 O 4 -NPs as a result of accumulation of insoluble manganese rather than Mn 2+ in the nervous tissue (Romashchenko et al, 2017) and use the level of the T1-weighted MRI signal to assess NP accumulation in the tissue.…”

Section: Methodsmentioning

confidence: 91%

“…The presence of manganese in brain tissue is apparent from the enhancement of the signal in T1 weighted MRI images, whose amplitude directly depends on manganese concentration (Lin, Koretsky, 1997). In particular, the microelement analysis of OB isolated from mice immediately after the MRI study showed a very close correlation between the intensity of the tomographic signal and the Mn content in the tissue (Romashchenko et al, 2017). All these observations provide grounds for considering the MRI signal amplitudes a semiquantitative indicator of the saturation of the brain tissue with manganese.…”

Section: Discussionmentioning

confidence: 99%

“…1, c) of Mn 3 O 4 -NPs correlate with manganese concentration in the samples (Romashchenko et al, 2017). In vivo experiments showed that the amplitude of the MRI signal in OB 12 hours after the intranasal application of Mn 3 O 4 -NPs was directly proportional to the manganese concentration in the tissue (Romashchenko et al, 2017). OB were taken for calibration, since the concentration of nanoparticles after the intranasal or inhalation administration is the highest in this region (Moshkin et al, 2014).…”

Section: Methodsmentioning

confidence: 99%

“…MRI studies. The accumulation of paramagnetic nanoparticles in brain divisions of the mouse was investigated using MRI on the Ultra-High-Definition BioSpec 117/16 USR Tomograph (Bruker, Germany) -11.7 T. MRI scans and the subsequent processing of the obtained images were carried out in accordance with previously developed protocols (Romashchenko et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

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The role of olfactory transport in the penetration of manganese oxide nanoparticles from blood into the brain

et al. 2019

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There is no doubt that various nanoparticles (NPs) can enter the brain from the nasal cavity. It is assumed that NPs can penetrate from blood into the central nervous system (CNS) only by breaking the blood–brain barrier (BBB). The accumulation of NPs in CNS can provoke many neurological diseases; therefore, the understanding of its mechanisms is of both academic and practical interest. Although hitting from the surface of the lungs into the bloodstream, NPs can accumulate in various mucous membranes, including the nasal mucosa. Thus, we cannot rule out the ability of NPs to be transported from the bloodstream to the brain through the olfactory uptake. To test this hypothesis, we used paramagnetic NPs of manganese oxide (Mn3O4-NPs), whose accumulation patterns in the mouse brain were recorded using T1-weighted magnetic resonance imaging. The effect of intranasal application of endocytosis and axonal transport inhibitors on the brain accumulation patterns of intranasally or intravenously injected Mn3O4-NPs was evaluated. A comparative analysis of the results showed that the transport of Mn3O4-NPs from the nasal cavity to the brain is more efficient than their local permeation through BBB into CNS from the bloodstream, for example with the accumulation of Mn3O4NPs in the dentate gyrus of the hippocampus, and through the capture and transport of NPs from the blood by olfactory epithelium cells. Also, experiments with the administration of chlorpromazine, a specific inhibitor of clathrin-dependent endocytosis, and methyl-β-cyclodextrin, inhibitor of the lipid rafts involved in the capture of substances by endothelium cells, showed differences in the mechanisms of NP uptake from the nasal cavity and from the bloodstream. In this study, we show a significant contribution of axonal transport to NP accumulation patterns in the brain, both from the nasal cavity and from the vascular bed. This explains the accumulation of different sorts of submicron particles (neurotropic viruses, insoluble xenobiotics, etc.), unable to pass BBB, in the brain. The results will add to the understanding of the pathogenesis of various neurodegenerative diseases and help studying the side effects of therapeutics administered intravenously.

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Section: Methodssupporting

confidence: 74%

Section: Methodsmentioning

confidence: 91%