Ceria Nanoparticles Synthesized With Aminocaproic Acid for the Treatment of Subarachnoid Hemorrhage.
Stroke
; 49(12): 3030-3038, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30571409
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Hemorragia Subaracnóidea
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Encéfalo
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Cério
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Morte Celular
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Fármacos Neuroprotetores
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Nanopartículas
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Ácido Aminocaproico
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Macrófagos
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Anti-Inflamatórios
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Neurônios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Stroke
Ano de publicação:
2018
Tipo de documento:
Article