Brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial

Mo Dan,1,2 Michael T Tseng,3 Peng Wu,4 Jason M Unrine,5 Eric A Grulke,4 Robert A Yokel1,21Department of Pharmaceutical Sciences, College of Pharmacy, 2Graduate Center for Toxicology, University of Kentucky, Lexington, KY, USA; 3Departments of Anatomical Sciences and Neurobiology, University of Louis...

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Autores principales:	Dan M, Tseng MT, Wu P, Unrine JM, Grulke EA, Yokel RA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/74f2ba54f7fe43cbb437edc6bf09a76c
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spelling	oai:doaj.org-article:74f2ba54f7fe43cbb437edc6bf09a76c2021-12-02T05:09:46ZBrain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial1176-91141178-2013https://doaj.org/article/74f2ba54f7fe43cbb437edc6bf09a76c2012-07-01T00:00:00Zhttp://www.dovepress.com/brain-microvascular-endothelial-cell-association-and-distribution-of-a-a10533https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Mo Dan,1,2 Michael T Tseng,3 Peng Wu,4 Jason M Unrine,5 Eric A Grulke,4 Robert A Yokel1,21Department of Pharmaceutical Sciences, College of Pharmacy, 2Graduate Center for Toxicology, University of Kentucky, Lexington, KY, USA; 3Departments of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA; 4Chemical and Materials Engineering Department, 5Department of Plant and Soil Science, University of Kentucky, Lexington, KY, USAPurpose: Ceria engineered nanomaterials (ENMs) have current commercial applications and both neuroprotective and toxic effects. Our hypothesis is that ceria ENMs can associate with brain capillary cells and/or cross the blood&ndash;brain barrier.Methods: An aqueous dispersion of ~5 nm ceria ENM was synthesized and characterized in house. Its uptake space in the Sprague Dawley rat brain was determined using the in situ brain perfusion technique at 15 and 20 mL/minute flow rates; 30, 100, and 500 &micro;g/mL ceria perfused for 120 seconds at 20 mL/minute; and 30 &micro;g/mL perfused for 20, 60, and 120 seconds at 20 mL/minute. The capillary depletion method and light and electron microscopy were used to determine its capillary cell and brain parenchymal association and localization.Results: The vascular space was not significantly affected by brain perfusion flow rate or ENM, demonstrating that this ceria ENM did not influence blood&ndash;brain barrier integrity. Cerium concentrations, determined by inductively coupled plasma mass spectrometry, were significantly higher in the choroid plexus than in eight brain regions in the 100 and 500 &micro;g/mL ceria perfusion groups. Ceria uptake into the eight brain regions was similar after 120-second perfusion of 30, 100, and 500 &micro;g ceria/mL. Ceria uptake space significantly increased in the eight brain regions and choroid plexus after 60 versus 20 seconds, and it was similar after 60 and 120 seconds. The capillary depletion method showed 99.4% &plusmn; 1.1% of the ceria ENM associated with the capillary fraction. Electron microscopy showed the ceria ENM located on the endothelial cell luminal surface.Conclusion: Ceria ENM association with brain capillary endothelial cells saturated between 20 and 60 seconds and ceria ENM brain uptake was not diffusion-mediated. During the 120-second ceria ENM perfusion, ceria ENM predominately associated with the surface of the brain capillary cells, providing the opportunity for its cell uptake or redistribution back into circulating blood.Keywords: ceria engineered nanomaterial, brain microvascular endothelial cell association, in situ brain perfusion, capillary depletionDan MTseng MTWu PUnrine JMGrulke EAYokel RADove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 4023-4036 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Dan M Tseng MT Wu P Unrine JM Grulke EA Yokel RA Brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial
description	Mo Dan,1,2 Michael T Tseng,3 Peng Wu,4 Jason M Unrine,5 Eric A Grulke,4 Robert A Yokel1,21Department of Pharmaceutical Sciences, College of Pharmacy, 2Graduate Center for Toxicology, University of Kentucky, Lexington, KY, USA; 3Departments of Anatomical Sciences and Neurobiology, University of Louisville, Louisville, KY, USA; 4Chemical and Materials Engineering Department, 5Department of Plant and Soil Science, University of Kentucky, Lexington, KY, USAPurpose: Ceria engineered nanomaterials (ENMs) have current commercial applications and both neuroprotective and toxic effects. Our hypothesis is that ceria ENMs can associate with brain capillary cells and/or cross the blood&ndash;brain barrier.Methods: An aqueous dispersion of ~5 nm ceria ENM was synthesized and characterized in house. Its uptake space in the Sprague Dawley rat brain was determined using the in situ brain perfusion technique at 15 and 20 mL/minute flow rates; 30, 100, and 500 &micro;g/mL ceria perfused for 120 seconds at 20 mL/minute; and 30 &micro;g/mL perfused for 20, 60, and 120 seconds at 20 mL/minute. The capillary depletion method and light and electron microscopy were used to determine its capillary cell and brain parenchymal association and localization.Results: The vascular space was not significantly affected by brain perfusion flow rate or ENM, demonstrating that this ceria ENM did not influence blood&ndash;brain barrier integrity. Cerium concentrations, determined by inductively coupled plasma mass spectrometry, were significantly higher in the choroid plexus than in eight brain regions in the 100 and 500 &micro;g/mL ceria perfusion groups. Ceria uptake into the eight brain regions was similar after 120-second perfusion of 30, 100, and 500 &micro;g ceria/mL. Ceria uptake space significantly increased in the eight brain regions and choroid plexus after 60 versus 20 seconds, and it was similar after 60 and 120 seconds. The capillary depletion method showed 99.4% &plusmn; 1.1% of the ceria ENM associated with the capillary fraction. Electron microscopy showed the ceria ENM located on the endothelial cell luminal surface.Conclusion: Ceria ENM association with brain capillary endothelial cells saturated between 20 and 60 seconds and ceria ENM brain uptake was not diffusion-mediated. During the 120-second ceria ENM perfusion, ceria ENM predominately associated with the surface of the brain capillary cells, providing the opportunity for its cell uptake or redistribution back into circulating blood.Keywords: ceria engineered nanomaterial, brain microvascular endothelial cell association, in situ brain perfusion, capillary depletion
format	article
author	Dan M Tseng MT Wu P Unrine JM Grulke EA Yokel RA
author_facet	Dan M Tseng MT Wu P Unrine JM Grulke EA Yokel RA
author_sort	Dan M
title	Brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial
title_short	Brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial
title_full	Brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial
title_fullStr	Brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial
title_full_unstemmed	Brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial
title_sort	brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/74f2ba54f7fe43cbb437edc6bf09a76c
work_keys_str_mv	AT danm brainmicrovascularendothelialcellassociationanddistributionofa5nmceriaengineerednanomaterial AT tsengmt brainmicrovascularendothelialcellassociationanddistributionofa5nmceriaengineerednanomaterial AT wup brainmicrovascularendothelialcellassociationanddistributionofa5nmceriaengineerednanomaterial AT unrinejm brainmicrovascularendothelialcellassociationanddistributionofa5nmceriaengineerednanomaterial AT grulkeea brainmicrovascularendothelialcellassociationanddistributionofa5nmceriaengineerednanomaterial AT yokelra brainmicrovascularendothelialcellassociationanddistributionofa5nmceriaengineerednanomaterial
_version_	1718400537058082816

Brain microvascular endothelial cell association and distribution of a 5 nm ceria engineered nanomaterial

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