Protecting neurons from cerebral ischemia/reperfusion injury via nanoparticle-mediated delivery of an siRNA to inhibit microglial neurotoxicity
Protecting neurons from cerebral ischemia/reperfusion injury via nanoparticle-mediated delivery of an siRNA to inhibit microglial neurotoxicity
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通过纳米颗粒介导的 siRNA 递送抑制小胶质细胞神经毒性，保护神经元免受脑缺血/再灌注损伤
DOI：
10.1016/j.biomaterials.2018.01.039
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发表时间：
2018-04-01
期刊：
影响因子：
14
通讯作者：
Wang, Jun
中科院分区：
文献类型：
--
作者：
Wang, Ye;Li, Shi-Yong;Wang, Jun
补体成分C3（C3）在脑缺血/再灌注（I/R）损伤后的小胶质细胞神经毒性中起核心作用。在这项研究中，我们专注于负载C3 siRNA的纳米颗粒（NPsiC 3）在抑制脑（I/R）损伤后小胶质细胞神经毒性中的作用。NPsiC 3抑制缺氧/复氧诱导的体外小胶质细胞C3表达增加。重要的是，用NPsic 3处理减少了C3 b在神经元上的沉积，并减少了缺氧/再氧条件下小胶质细胞介导的神经元损伤。纳米颗粒可以有效地将C3-siRNA从血液中穿过血脑屏障（BBB）递送到缺血半暗带，并显著降低小胶质细胞和缺血脑组织中C3的表达，同时减少半暗带中浸润的炎性细胞数量和促炎因子浓度。此外，NPsic 3还防止神经元凋亡，减少缺血区的体积，并大大改善VIZ损伤后的功能恢复。因此，NPsiC 3诱导的小胶质细胞神经毒性的抑制代表了治疗脑I/R损伤的新的治疗策略。(C)2018爱思唯尔有限公司版权所有
Complement component C3 (C3) plays a central role in microglial neurotoxicity following cerebral ischemia/reperfusion (I/R) injury. In this study, we focused on the role of nanoparticles loaded with C3 siRNA (NPsiC3) in inhibiting microglial neurotoxicity after brain (I/R) injury. NPsiC3 inhibited the hypoxia/re-oxygenation-induced increase in C3 expression in microglia in vitro. Importantly, treatment with NPsic3 decreased C3b deposition on neurons and reduced microglia-mediated neuronal damage under hypoxia/re-oxygen conditions. Nanoparticles could effectively deliver C3-siRNA from the blood into ischemic penumbra across the blood-brain barrier (BBB) and significantly decrease C3 expression in microglia and ischemic brain tissue, while reducing the number of infiltrating inflammatory cells and the concentration of pro-inflammatory factors in the penumbra. Furthermore, NPsic3 also prevented neuronal apoptosis, reduced the volume of the ischemic zone, and substantially improved functional recovery after VIZ injury. Therefore, the NPsiC3-induced inhibition of microglial neurotoxicity represents a novel therapeutic strategy for treating brain I/R injury. (C) 2018 Elsevier Ltd. All rights reserved.