Extremely Low-Frequency Electromagnetic Stimulation (ELF-EMS) Improves Neurological Outcome and Reduces Microglial Reactivity in a Rodent Model of Global Transient Stroke

Abstract

Extremely low-frequency electromagnetic stimulation (ELF-EMS) was demonstrated to be significantly beneficial in rodent models of permanent stroke. The mechanism involved enhanced cerebrovascular perfusion and endothelial cell nitric oxide production. However, the possible effect on the neuroinflammatory response and its efficacy in reperfusion stroke models remains unclear. To evaluate ELF-EMS effectiveness and possible immunomodulatory response, we studied neurological outcome, behavior, neuronal survival, and glial reactivity in a rodent model of global transient stroke treated with 13.5 mT/60 Hz. Next, we studied microglial cells migration and, in organotypic hippocampal brain slices, we assessed neuronal survival and microglia reactivity. ELF-EMS improved the neurological score and behavior in the ischemia-reperfusion model. It also improved neuronal survival and decreased glia reactivity in the hippocampus, with microglia showing the first signs of treatment effect. In vitro ELF-EMS decreased (Lipopolysaccharide) LPS and ATP-induced microglia migration in both scratch and transwell assay. Additionally, in hippocampal brain slices, reduced microglial reactivity, improved neuronal survival, and modulation of inflammation-related markers was observed. Our study is the first to show that an EMF treatment has a direct impact on microglial migration. Furthermore, ELF-EMS has beneficial effects in an ischemia/reperfusion model, which indicates that this treatment has clinical potential as a new treatment against ischemic stroke.

System-level biological effects of extremely low-frequency electromagnetic fields: an in vivo experimental review

“…In a follow-up study on post-stroke patients, they found that exposure to ELF-EMF led to a significant elevation in the levels of growth factors and cytokines associated with neuroplasticity and facilitated a notable improvement in functional recovery (Cichoń et al, 2018). In animal models of transient stroke, the results indicated that exposure to ELF-EMF enhanced the neurological assessment and behavioral outcomes, exhibited a positive impact on neuronal viability, and contributed to a reduction in glial reactivity within the hippocampus, which confirmed the potential of EMF as a clinical therapy (Moya-Gómez et al, 2023).…”

Neuroprotective Effects of Aucubin against Cerebral Ischemia and Ischemia Injury through the Inhibition of the TLR4/NF-κB Inflammatory Signaling Pathway in Gerbils

“…Accumulating evidence has revealed that glial cells play a pivotal role in cerebral IR injury [ 27 , 28 , 29 ]. Cerebral IR induces the reaction of microglia and astrocytes, as evidenced by the presence of enlarged cell bodies and hypertrophic processes, and they secrete diverse proinflammatory mediators, which contribute to severe neuroinflammatory responses and the aggravation of cerebral IR injury [ 30 , 31 ].…”