Autophagy is involved in nanoalumina-induced cerebrovascular toxicity

Lei Chen, Bei Zhang, Michal Toborek

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

The current study focused on blood-brain barrier disruption and neurovascular damage induced by engineered nanomaterials. Exposure to nanoalumina, but not to nanocarbon, induced a dose-dependent mitochondrial potential collapse, increased autophagy of brain endothelial cells, and decreased expression of the tight-junction proteins occludin and claudin-5. Inhibition of autophagy by pretreatment with Wortmannin attenuated the effects of nanoalumina on decreased claudin-5 expression; however, it did not affect the disruption of occludin. These findings were confirmed in mice by administration of nanoalumina into the cerebral circulation. Systemic treatment with nanoalumina elevated autophagy-related genes and autophagic activity in the brain, decreased tight-junction protein expression, and elevated blood-brain barrier permeability. Finally, exposure to nanoalumina, but not to nanocarbon, increased brain infarct volume in mice subjected to a focal ischemic stroke model. Overall, our study reveals that autophagy constitutes an important mechanism involved in nanoalumina-induced neurovascular toxicity in the central nervous system. From the Clinical Editor: In this paper, the effects of nanoalumina on the permeability of the blood-brain barrier is reported, suggesting that autophagy is an important mechanism in nanoalumina-induced neurovascular toxicity.

Original languageEnglish (US)
Pages (from-to)212-221
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume9
Issue number2
DOIs
StatePublished - Feb 2013

Keywords

  • Autophagy
  • Blood-brain barrier
  • Central nervous system
  • Nanoalumina

ASJC Scopus subject areas

  • Molecular Medicine
  • Bioengineering
  • Biomedical Engineering
  • Materials Science(all)
  • Medicine (miscellaneous)
  • Pharmaceutical Science

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