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.

Microwave radiation has been widely used in various fields, such as communication, industry, medical treatment, and military applications. Microwave radiation may cause injuries to both the structures and functions of various organs, such as the brain, heart, reproductive organs, and endocrine organs, which endanger human health. Therefore, it is both theoretically and clinically important to conduct studies on the biological effects induced by microwave radiation. The successful establishment of injury models is of great importance to the reliability and reproducibility of these studies. In this article, we review the microwave exposure conditions, subjects used to establish injury models, the methods used for the assessment of the injuries, and the indicators implemented to evaluate the success of injury model establishment in studies on biological effects induced by microwave radiation.

The reproductive system has been increasingly implicated as a sensitive target of microwave radiation. Oxidative stress plays a critical role in microwave radiation -induced reproductive damage, though precise mechanisms are obscure. Metformin, a widely used antidiabetic drug, has emerged as an efficient antioxidant against a variety of oxidative injuries. In the present study, we hypothesized that metformin can function as an antioxidant and protect the reproductive system from microwave radiation. To test this hypothesis, rats were exposed to 2.856 GHz microwave radiation for 6 weeks to simulate real-life exposure to high-frequency microwave radiation. Our results showed that exposure to 2.856 GHz microwave radiation elicited serum hormone disorder, decreased sperm motility, and depleted sperm energy, and it induced abnormalities of testicular structure as well as mitochondrial impairment. Metformin was found to effectively protect the reproductive system against structural and functional impairments caused by microwave radiation. In particular, metformin can ameliorate microwave-radiation-induced oxidative injury and mitigate apoptosis in the testis, as determined by glutathione/-oxidized glutathione (GSH/GSSG), lipid peroxidation, and protein expression of heme oxygenase-1 (HO-1). These findings demonstrated that exposure to 2.856 GHz microwave radiation induces obvious structural and functional impairments of the male reproductive system, and suggested that metformin can function as a promising antioxidant to inhibit microwave-radiation-induced harmful effects by inhibiting oxidative stress and apoptosis.

With the rapidly increasing application of microwave technologies, the anxiety and speculation about microwave induced potential health hazards has been attracting more and more attention. In our daily life, people are exposed to complex environments with multi-frequency microwaves, especially L band and C band microwaves, which are commonly used in communications. In this study, we exposed rats to 1.5 GHz (L10), 4.3 GHz (C10) or multi-frequency (LC10) microwaves at an average power density of 10 mW/cm². Both single and multi-frequency microwaves induced slight pathological changes in the thymus and spleen. Additionally, the white blood cells (WBCs) and lymphocytes in peripheral blood were decreased at 6 h and 7 d after exposure, suggesting immune suppressive responses were induced. Among lymphocytes, the B lymphocytes were increased while the T lymphocytes were decreased at 7 d after exposure in the C10 and LC10 groups, but not in the L10 group. Moreover, multi-frequency microwaves regulated the B and T lymphocytes more strongly than the C band microwave. The results of transcriptomics and proteomics showed that both single and multi-frequency microwaves regulated numerous genes associated with immune regulation and cellular metabolism in peripheral blood and in the spleen. However, multi-frequency microwaves altered the expression of many more genes and proteins. Moreover, multi-frequency microwaves down-regulated T lymphocytes’ development, differentiation and activation-associated genes, while they up-regulated B lymphocytes’ activation-related genes. In conclusion, multi-frequency microwaves of 1.5 GHz and 4.3 GHz produced immune suppressive responses via regulating immune regulation and cellular metabolism-associated genes. Our findings provide meaningful information for exploring potential mechanisms underlying multi-frequency induced immune suppression.

It is well-known that microwaves produce both thermal and nonthermal effects. Microwave ablation can produce thermal effects to activate the body’s immune system and has been widely used in cancer therapy. However, the nonthermal effects of microwaves on the immune system are still largely unexplored. In the present study, we exposed rats to multifrequency microwaves of 2.8 GHz and 9.3 GHz with an average power density of 10 mW/cm², which are widely used in our daily life, to investigate the biological effects on the immune system and its potential mechanisms. Both single-frequency microwaves and multifrequency microwaves caused obvious pathological alterations in the thymus and spleen at seven days after exposure, while multifrequency microwaves produced more pronounced injuries. Unexpectedly, multifrequency microwave exposure increased the number of both leukocytes and lymphocytes in the peripheral blood and upregulated the proportion of B lymphocytes among the total lymphocytes, indicating activation of the immune response. Our data also showed that the cytokines associated with the proliferation and activation of B lymphocytes, including interleukin (IL)-1α, IL-1β and IL-4, were elevated at six hours after exposure, which might contribute to the increase in B lymphocytes at seven days after exposure. Moreover, multifrequency microwave exposure upregulated the mRNA and protein expression of B cell activation-associated genes in peripheral blood. In addition to immune-associated genes, multifrequency microwaves mainly affected the expression of genes related to DNA duplication, cellular metabolism and signal transduction in the peripheral blood and spleen. In conclusion, multifrequency microwaves with 2.8 GHz and 9.3 GHz caused reversible injuries of the thymus and spleen but activated immune cells in the peripheral blood by upregulating mRNA and protein expression, as well as cytokine release. These results not only uncovered the biological effects of multifrequency microwave on the immune system, but also provide critical clues to explore the potential mechanisms.