Autophagy is involved in nanoalumina-induced cerebrovascular toxicity

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 EditorIn 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.

Exposure to nanoalumina induces a dose-dependent mitochondrial potential collapse, increases autophagy of brain endothelial cells, and decreases expression of tight-junction proteins. These changes contribute to elevated blood–brain barrier permeability and increased brain infarct volume in mice subjected to a focal ischemic stroke model. Overall, these results indicate that autophagy constitutes an important mechanism involved in nanoalumina-induced neurovascular toxicity in the central nervous system.Figure optionsDownload high-quality image (274 K)Download as PowerPoint slide