Neuroprotective mechanisms of cerium oxide nanoparticles in a mouse hippocampal brain slice model of ischemia

Cerium oxide nanoparticles (nanoceria) are widely used as catalysts in industrial applications because of their potent free radical-scavenging properties. Given that free radicals play a prominent role in the pathology of many neurological diseases, we explored the use of nanoceria as a potential th...

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Published in:	Free radical biology & medicine Vol. 51; no. 6; pp. 1155 - 1163
Main Authors:	Estevez, A.Y., Pritchard, S., Harper, K., Aston, J.W., Lynch, A., Lucky, J.J., Ludington, J.S., Chatani, P., Mosenthal, W.P., Leiter, J.C., Andreescu, S., Erlichman, J.S.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 15-09-2011
Subjects:	Animal models Animals Apoptosis - drug effects brain Brain injury Brain Ischemia - drug therapy Brain Ischemia - metabolism Brain Ischemia - pathology Brain slice preparation Catalysts Cell death Cerebral ischemia cerium Cerium - chemistry Cerium - pharmacology Disease Models, Animal Free Radical Scavengers - pharmacology Free radicals Hippocampus Hippocampus - drug effects Hippocampus - metabolism Hippocampus - pathology Industrial applications Ischemia Mice Mouse Nanoceria nanoparticles Nanoparticles - chemistry Nanoparticles - therapeutic use nervous system diseases Neurological diseases Neuroprotection Neuroprotective Agents - pharmacology neuroprotective effect Nitric oxide Nitric Oxide - metabolism Nitrosylation nitrotyrosine Oxidative Stress - drug effects oxides Peroxynitrite Peroxynitrous Acid - chemistry Peroxynitrous Acid - metabolism proteins Reactive oxygen species Stroke Superoxide superoxide anion Superoxides - metabolism Therapeutic applications Tyrosine Tyrosine - analogs & derivatives Tyrosine - metabolism Nanoceria Cerebral ischemia Peroxynitrite Free radicals Mouse Nitric oxide Nitrosylation Superoxide
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Summary:	Cerium oxide nanoparticles (nanoceria) are widely used as catalysts in industrial applications because of their potent free radical-scavenging properties. Given that free radicals play a prominent role in the pathology of many neurological diseases, we explored the use of nanoceria as a potential therapeutic agent for stroke. Using a mouse hippocampal brain slice model of cerebral ischemia, we show here that ceria nanoparticles reduce ischemic cell death by approximately 50%. The neuroprotective effects of nanoceria were due to a modest reduction in reactive oxygen species, in general, and ~ 15% reductions in the concentrations of superoxide (O 2 •−) and nitric oxide, specifically. Moreover, treatment with nanoceria markedly decreased (~ 70% reduction) the levels of ischemia-induced 3-nitrotyrosine, a modification to tyrosine residues in proteins induced by the peroxynitrite radical. These findings suggest that scavenging of peroxynitrite may be an important mechanism by which cerium oxide nanoparticles mitigate ischemic brain injury. Peroxynitrite plays a pivotal role in the dissemination of oxidative injury in biological tissues. Therefore, nanoceria may be useful as a therapeutic intervention to reduce oxidative and nitrosative damage after a stroke.
Bibliography:	http://dx.doi.org/10.1016/j.freeradbiomed.2011.06.006 ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0891-5849 1873-4596
DOI:	10.1016/j.freeradbiomed.2011.06.006