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Ceria Nanoparticles Synthesized With Aminocaproic Acid for the Treatment of Subarachnoid Hemorrhage

Authors
Jeong, Han-GilCha, Bong GeunKang, Dong-WanKim, Do YeonKi, Seul KiKim, Song I.Han, Ju HeeYang, WookjinKim, Chi KyungKim, JaeyunLee, Seung-Hoon
Issue Date
12월-2018
Publisher
LIPPINCOTT WILLIAMS & WILKINS
Keywords
nanomedicine; neuroprotective agents; reactive oxygen species; stroke; subarachnoid hemorrhage
Citation
STROKE, v.49, no.12, pp.3030 - 3038
Indexed
SCIE
SCOPUS
Journal Title
STROKE
Volume
49
Number
12
Start Page
3030
End Page
3038
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/71481
DOI
10.1161/STROKEAHA.118.022631
ISSN
0039-2499
Abstract
Background and Purpose-Despite early aneurysm repair and aggressive management for complications, subarachnoid hemorrhage (SAH) results in at least 25% mortality rate and 50% persistent neurological deficit. We investigated whether ceria nanoparticles which have potent antioxidative activities can protect against subarachnoid hemorrhage via attenuating fatal brain injuries. Methods-Uniform, 3 nm, water-dispersed ceria nanoparticles were prepared from short sol-gel reaction of cerium (III) ions with aminocaproic acid in aqueous phase. SAH was induced by endovascular perforation of middle cerebral artery of rats. A single dose of ceria nanoparticles (0.5 mg Ce/kg) or saline control was randomly administered intravenously at an hour post-SAH. Neuronal death, macrophage infiltration, SAH grade, and brain edema were evaluated at 72 hours. Mortality and neurological function were assessed for 14 days. Results-The obtained ceria nanoparticles with high Ce3+ to Ce4+ ratio demonstrated potent antioxidative, cytoprotective, and anti-inflammatory activities in vitro. In rodent SAH models, the severity of hemorrhage was comparable between the ceria nanoparticles- and saline-treated groups. However, ceria nanoparticles significantly reduced neuronal death, macrophage infiltration, and brain edema after SAH. Ceria nanoparticles successfully improved survival rates (88.2% in the ceria nanoparticles group versus 21.1% in the control group; P<0.001) and neurological outcomes (modified Garcia score: 12.1 +/- 0.5 in the ceria nanoparticles group versus 4.4 +/- 0.5 in the control group; P<0.001) of the animals with SAH. Conclusions-Ceria nanoparticles, totally synthesized in aqueous phase using aminocaproic acid, demonstrated promising results against SAH via potent antioxidative, neuroprotective and anti-inflammatory activities. Given the obvious limitations of current therapies for SAH, ceria nanoparticles can be a potential therapeutic agent which might result in a paradigm shift in SAH treatment. Visual Overview-An online visual overview is available for this article.
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