Cerebral ischemic stroke stimulates excessive reactive oxygen species, which lead to blood–brain-barrier disruption, neuron death, and aggravated cerebral infarction. Thus, it is critical to develop an antioxidant strategy for stroke treatment. Herein, we report a dietary strategy to promote stroke healing using iron oxide (Fe₃O₄) nanoparticles with intrinsic enzyme-like activities. We find that Fe₃O₄ nanozymes exhibit triple enzyme-like activities, peroxidase, catalase, and superoxide dismutase, thus potentially possessing the ability to regulate the ROS level. Importantly, intragastric administration of PEG-modified Fe₃O₄ nanozymes significantly reduces cerebral infarction and neuronal death in a rodent model following cerebral ischemic stroke. Ex vivo analysis shows that PEG-modified Fe₃O₄ nanozymes localize in the cerebral vasculature, ameliorate local redox state with decreased malondialdehyde and increased Cu/Zn SOD, and facilitate blood–brain-barrier recovery by elevating ZO-1 and Claudin-5 in the hippocampus. Altogether, our results suggest that dietary PEG-modified Fe₃O₄ nanozymes can facilitate blood–brain-barrier reconstruction and protect neurons following ischemic stroke.

中文翻译：

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饮食中的Fe ₃ O ₄纳米酶可预防神经缺血性脑卒中对神经元和血脑屏障完整性的伤害

脑缺血性中风会刺激活性氧过多，从而导致血脑屏障破坏，神经元死亡和脑梗塞加重。因此，开发用于中风治疗的抗氧化剂策略至关重要。在这里，我们报告了一种饮食策略，以使用具有内在酶样活性的氧化铁（Fe ₃ O ₄）纳米颗粒来促进中风康复。我们发现，Fe ₃ O ₄纳米酶表现出三重酶样活性，过氧化物酶，过氧化氢酶和超氧化物歧化酶，因此潜在地具有调节ROS水平的能力。重要的是，胃内施用PEG修饰的Fe ₃ O ₄在啮齿类动物脑缺血性中风后，纳米酶显着减少了脑梗塞和神经元死亡。离体分析表明，PEG修饰的Fe ₃ O ₄纳米酶位于脑血管中，改善了局部氧化还原状态，丙二醛减少，铜/锌超氧化物歧化酶增加，并通过提高ZO-1和Claudin-5促进血脑屏障恢复在海马中。总之，我们的结果表明，饮食性PEG修饰的Fe ₃ O ₄纳米酶可以促进缺血性卒中后的血脑屏障重建并保护神经元。