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In vitro evidence of dysregulation of blood–brain barrier function after acute and repeated/long-term exposure to TiO2 nanoparticles

Paper ID Volume ID Publish Year Pages File Format Full-Text
7054 530 2012 11 PDF Available
Title
In vitro evidence of dysregulation of blood–brain barrier function after acute and repeated/long-term exposure to TiO2 nanoparticles
Abstract

The effects of titanium dioxide nanoparticles (TiO2 NPs) on blood–brain barrier (BBB) function are unknown. Here, we report such evidence of adverse effects after in vitro exposure of a rat primary cell-based BBB model to NPs. BBB integrity was studied by measuring the flux of sucrose through the monolayer. P-glycoprotein (P-gp) activity was assessed by measuring the passage of vinblastine. Transcription profiles of P-gp and other ABC transporters as well as of cytokines were investigated by real-time PCR. Electron microscopy and particle-induced X-ray emission measurements were performed. We compared several exposure modalities, from early to chronic, mimicking a brain-to-blood transport or a systemic contamination. In the first case, BBB integrity was preserved, but P-gp activity of endothelial cells (BECs) was reduced. In the second case, BBB integrity and P-gp function were impaired from 5 μg/mL for 24 h and expression of tight junction proteins and efflux transporters was modulated. An inflammatory response had repercussions on ABC transporter expression of glial cells. We demonstrate that NPs accumulated in BECs and crossed the cell monolayer. These findings suggest that there is an immunoregulatory loop between inflammatory components, BECs and glial cells in the dysfunction of the BBB during exposure to TiO2 NPs.

Keywords
Titanium dioxide; Nanoparticles; Blood–brain barrier; Nanotoxicology; Inflammation; ABC transporters
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In vitro evidence of dysregulation of blood–brain barrier function after acute and repeated/long-term exposure to TiO2 nanoparticles
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 3, January 2012, Pages 886–896
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us