Biology Department, St. Lawrence University, Canton, NY, USA.
Free Radic Biol Med. 2011 Sep 15;51(6):1155-63. doi: 10.1016/j.freeradbiomed.2011.06.006. Epub 2011 Jun 12.
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.
氧化铈纳米颗粒（纳米氧化铈）因其具有强大的自由基清除特性，被广泛用作工业应用中的催化剂。鉴于自由基在许多神经疾病的病理过程中起着重要作用，我们探索了使用纳米氧化铈作为治疗中风的潜在治疗剂。我们在这里使用小鼠海马脑片脑缺血模型表明，纳米氧化铈可将缺血性细胞死亡减少约 50%。纳米氧化铈的神经保护作用归因于活性氧的适度减少，一般来说，超氧化物（O2（•-））和一氧化氮（NO）的浓度分别降低了约 15%。此外，用纳米氧化铈处理可显著降低（约 70%的降低）缺血诱导的 3-硝基酪氨酸的水平，这是过氧亚硝酸盐自由基诱导的蛋白质酪氨酸残基的修饰。这些发现表明，过氧亚硝酸盐的清除可能是氧化铈纳米颗粒减轻缺血性脑损伤的重要机制。过氧亚硝酸盐在生物组织中氧化损伤的传播中起着关键作用。因此，纳米氧化铈可用作治疗干预措施，以减少中风后的氧化和硝化损伤。
