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Journal of Neuroimmune Pharmacology

, Volume 3, Issue 4, pp 286–295 | Cite as

Manufactured Aluminum Oxide Nanoparticles Decrease Expression of Tight Junction Proteins in Brain Vasculature

  • Lei Chen
  • Robert A. Yokel
  • Bernhard Hennig
  • Michal ToborekEmail author
Original Article

Abstract

Manufactured nanoparticles of aluminum oxide (nano-alumina) have been widely used in the environment; however, their potential toxicity provides a growing concern for human health. The present study focuses on the hypothesis that nano-alumina can affect the blood-brain barrier and induce endothelial toxicity. In the first series of experiments, human brain microvascular endothelial cells (HBMEC) were exposed to alumina and control nanoparticles in dose- and time-responsive manners. Treatment with nano-alumina markedly reduced HBMEC viability, altered mitochondrial potential, increased cellular oxidation, and decreased tight junction protein expression as compared to control nanoparticles. Alterations of tight junction protein levels were prevented by cellular enrichment with glutathione. In the second series of experiments, rats were infused with nano-alumina at the dose of 29 mg/kg and the brains were stained for expression of tight junction proteins. Treatment with nano-alumina resulted in a marked fragmentation and disruption of integrity of claudin-5 and occludin. These results indicate that cerebral vasculature can be affected by nano-alumina. In addition, our data indicate that alterations of mitochondrial functions may be the underlying mechanism of nano-alumina toxicity.

Keywords

manufactured nanoparticles nano-alumina blood-brain barrier tight junctions 

Notes

Acknowledgements

Supported in part by Kentucky Science and Engineering Foundation (KSEF-07-RDE-010), P42 ES 07380, MH63022, MH072567, and NS39254.

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Lei Chen
    • 1
  • Robert A. Yokel
    • 2
  • Bernhard Hennig
    • 3
  • Michal Toborek
    • 1
    Email author
  1. 1.Molecular Neuroscience and Vascular Biology Laboratory, Department of NeurosurgeryUniversity of Kentucky Medical CenterLexingtonUSA
  2. 2.College of PharmacyUniversity of KentuckyLexingtonUSA
  3. 3.College of AgricultureUniversity of KentuckyLexingtonUSA

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