Electromagnetic pulse (EMP) radiation was reported to be harmful to hippocampal neurons. However, the mechanism underlying EMP-induced neuronal damage remains unclear. In this paper, for the first time, we attempted to investigate the involvement of ferroptosis in EMP-induced neuronal damage and its underlying mechanism. In vivo studies were conducted with a rat model to examine the association of ferroptosis and EMP-induced hippocampal neuronal damage. Moreover, in vitro studies were conducted with HT22 neurons to investigate the underlying mechanism of EMP-induced neuronal ferroptosis. In vivo results showed that EMP could induce learning and memory impairment of rats, ferroptotic morphological damages to mitochondria, accumulation of malonaldehyde (MDA) and iron, overexpression of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA, and downregulation of GPX4 protein in rat hippocampus. In vitro results showed that EMP could induce neuronal death, MDA accumulation, iron overload, PTGS2 overexpression, and GPX4 downregulation in HT22 neurons. These adverse effects could be reversed by either lipid peroxides scavenger ferrostatin-1 or overexpression of GPX4. These results suggest that EMP radiation can induce ferroptosis in hippocampal neurons via a vicious cycle of lipid peroxides accumulation and GSH/GPX4 axis downregulation. Lipid peroxides and the GSH/GPX4 axis provide potential effective intervention targets to EMP-induced hippocampal neuronal damage.

Previous studies have suggested that microwave (MW) radiation with certain parameters can induce spatial memory deficits. However, the effect of MW on the topological organization of the brain network is still unknown. This work aimed to investigate the topological organization of the brain network in rats with spatial memory impairments induced by acute microwave (MW) radiation. The Morris water maze (MWM) test and resting-state functional magnetic resonance imaging were performed to estimate the spatial memory ability and brain network topological organization of the rats after MW exposure. Compared with the sham group, the rats exposed to 30 mW/cm² 1.5 GHz MW radiation exhibited a significantly decreased normalized clustering coefficient (γ) (p = 0.002) 1 d after the exposure and a prolonged average escape latency (AEL) (p = 0.014) 3 d after the exposure. Moreover, after 10 mW/cm² 1.5 GHz MW radiation, a significantly decreased γ (p = 0.003) was also observed in the rats, without any changes in AEL. In contrast, no adverse effects on AEL or topological parameters were observed after 9.375 GHz MW radiation. In conclusion, the rats with spatial memory deficits induced by MW radiation exhibited disruptions in the topological organization of the brain network. Moreover, these topological organization disruptions emerged earlier than behavioral symptom onset and could even be found in the rats without a decline in the performance of the spatial memory task. Therefore, it is possible to use the topological parameters of the brain network as early and sensitive indicators of the spatial memory impairments induced by acute MW radiation.