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.

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Insulin-like growth factor 1 (IGF-1) is a well-known growth factor with well-defined neuroprotective effects against cerebral ischemia. However, the age-dependent differences in the expression of IGF-1 and its receptor (IGF-1R) in the brain following transient cerebral ischemia (TCI) have not been elucidated. In the present study, the differences in IGF-1 and IGF-1R in the gerbil hippocampal CA1 region of young and adult gerbils 5 min following TCI were determined. Seven days following TCI, the neuronal death in the hippocampal CA1 region of young gerbils was significantly less than that observed in adult gerbils. In addition, the immunoreactivity, and levels of IGF-1 and IGF-1R in the CA1 region of the normal young were higher than those in the normal adult. Four days following TCI, the immunoreactivity, and protein levels of IGF-1 and IGF-1R were markedly decreased in the adult group. By contrast, in the young group, the immunoreactivity and expression levels were much greater than those in the adult group. However, 7 days following TCI, all immunoreactivity and expression levels were markedly decreased when compared with those in the normal adult and young groups. In addition, the immunoreactivity and expression levels in the young groups were significantly higher than those of the adult groups. In conclusion, the present study demonstrated that the higher and sustained expression of IGF-1 and IGF-1R in the young gerbil hippocampal CA1 region following TCI may be associated with the reduced neuronal death compared to that in the adults.