Ceria Nanoparticles Synthesized With Aminocaproic Acid for the Treatment of Subarachnoid Hemorrhage
Ceria Nanoparticles Synthesized With Aminocaproic Acid for the Treatment of Subarachnoid Hemorrhage
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DOI：
10.1161/strokeaha.118.022631
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发表时间：
2018-12-01
期刊：
影响因子：
8.3
通讯作者：
Lee, Seung-Hoon
中科院分区：
文献类型：
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作者：
Jeong, Han-Gil;Cha, Bong Geun;Lee, Seung-Hoon
背景和目的：尽管早期动脉瘤修复和积极治疗并发症，蛛网膜下腔出血（SAH）导致至少25%的死亡率和50%的持续性神经功能缺损。我们研究了具有强抗氧化活性的氧化铈纳米颗粒是否可以通过减轻致死性脑损伤来预防蛛网膜下腔出血。方法：将铈（III）离子与氨基己酸在水相中进行短时间溶胶-凝胶反应，制备均匀、粒径为3 nm的水分散二氧化铈纳米颗粒。大鼠大脑中动脉血管内穿孔诱发SAH。在sah后1小时随机静脉给予单剂量的二氧化铈纳米颗粒（0.5 mg Ce/kg）或生理盐水对照。72小时后评估神经元死亡、巨噬细胞浸润、SAH分级和脑水肿。随访14天，评估死亡率和神经功能。结果：制备的高Ce3+ / Ce4+比的氧化铈纳米颗粒具有较强的体外抗氧化、细胞保护和抗炎活性。在啮齿动物SAH模型中，二氧化铈纳米粒子组和盐处理组的出血严重程度相当。然而，氧化铈纳米颗粒可显著减少SAH后的神经元死亡、巨噬细胞浸润和脑水肿。氧化铈纳米颗粒成功地提高了生存率（氧化铈纳米颗粒组为88.2%，对照组为21.1%）
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