This study investigated whether nitroxide radical (4-amino-TEMPOL)–containing nanoparticles (RNPs; antioxidant nanomedicine) can prevent neurovascular unit impairment caused by reactive oxygen species (ROS) after cerebral ischemia-reperfusion.

C57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO). The mice were randomly divided and administered intra-arterial RNPs injection (9 mg/kg, 7 μM/kg), edaravone (3 mg/kg, 17 μM/kg), or phosphate-buffered saline (control group). Survival rate and neurological score were evaluated 24 h post-injection. RNPs distribution was determined using immunofluorescence staining and blood–brain barrier (BBB) disruption using Evans blue extravasation assay. Effect of RNPs and edaravone on microglia polarization into microglia M1 and M2 was evaluated. We also determined multiple ROS-scavenging activities in brain homogenates of RNPs- and edaravone-treated animals using an electron spin resonance-based spin-trapping method.

Compared with edaravone, RNPs significantly improved the survival rate and neurological deficit, inhibited BBB disruption and supported polarization of microglia into M2 microglia. RNPs were localized in endothelial cells, the perivascular space, neuronal cell cytoplasm, astrocytes, and microglia. Scavenging capacities of hydroxyl, alkoxyl, and peroxyl radicals were significantly higher in the RNPs-treated group.

RNPs show promising results as a future neuroprotective nanomedicine approach for cerebral ischemia-reperfusion injury.

本研究调查了含氮氧自由基（4-氨基-TEMPOL）的纳米颗粒（RNPs；抗氧化纳米药物）是否可以预防脑缺血再灌注后活性氧（ROS）引起的神经血管单元损伤。

C57BL/6J 小鼠经历了短暂的大脑中动脉闭塞 (tMCAO)。将小鼠随机分开并给予动脉内 RNPs 注射（9 mg/kg，7 μM/kg）、依达拉奉（3 mg/kg，17 μM/kg）或磷酸盐缓冲盐水（对照组）。注射后 24 小时评估存活率和神经系统评分。RNPs 分布使用免疫荧光染色和血脑屏障 (BBB) 破坏使用伊文思蓝外渗测定法确定。评估了 RNP 和依达拉奉对小胶质细胞极化成小胶质细胞 M1 和 M2 的影响。我们还使用基于电子自旋共振的自旋捕获方法确定了 RNPs 和依达拉奉治疗动物脑匀浆中的多种 ROS 清除活性。

与依达拉奉相比，RNPs 显着提高存活率和神经功能缺损，抑制 BBB 破坏并支持小胶质细胞向 M2 小胶质细胞的极化。RNP 位于内皮细胞、血管周围间隙、神经元细胞质、星形胶质细胞和小胶质细胞中。羟基、烷氧基和过氧自由基的清除能力在 RNPs 治疗组中显着更高。

RNPs 作为未来脑缺血再灌注损伤的神经保护纳米医学方法显示出有希望的结果。