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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Autophagy is involved in nanoalumina-induced cerebrovascular toxicity.

Authors: Chen, Lei; Zhang, Bei; Toborek, Michal

Published In Nanomedicine, (2013 Feb)

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.

PubMed ID: 22687898 Exiting the NIEHS site

MeSH Terms: Aluminum Oxide/chemistry; Aluminum Oxide/toxicity*; Animals; Autophagy/drug effects*; Blood-Brain Barrier/drug effects; Blood-Brain Barrier/metabolism; Brain/blood supply; Brain/drug effects*; Brain/metabolism; Brain/pathology*; Cell Line; Cerebrovascular Circulation/drug effects*; Gene Expression Regulation/drug effects; Humans; Infarction, Middle Cerebral Artery/pathology; Male; Membrane Potential, Mitochondrial/drug effects; Mice; Mice, Inbred C57BL; Nanostructures/chemistry; Nanostructures/toxicity*; Permeability; Proteolysis/drug effects

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