Format

Send to

Choose Destination
Nanomedicine. 2013 Feb;9(2):212-21. doi: 10.1016/j.nano.2012.05.017. Epub 2012 Jun 9.

Autophagy is involved in nanoalumina-induced cerebrovascular toxicity.

Author information

1
Molecular Neuroscience and Vascular Biology Laboratory, Department of Neurosurgery and Graduate Center for Nutritional Sciences, University of Kentucky Medical Center, Lexington, Kentucky, USA.

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.

PMID:
22687898
PMCID:
PMC3482418
DOI:
10.1016/j.nano.2012.05.017
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center