Autophagy is involved in nanoalumina-induced cerebrovascular toxicity

作者：Chen Lei; Zhang Bei; Toborek Michal^*

来源：Nanomedicine: Nanotechnology, Biology and Medicine , 2013, 9(2): 212-221.

DOI：10.1016/j.nano.2012.05.017

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

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. %26lt;br%26gt;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.

• 出版日期2013-2