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.

Background/Objectives: Angiogenesis is the multistep process of the formation of new blood vessels. It is beneficial in scenarios that require tissue repair and regeneration, such as wound healing, bone fracture repair, and recovery from ischemic injuries like stroke, where new blood vessel formation restores oxygen and nutrient supply to damaged areas. Extremely low-frequency electromagnetic stimulation (ELF-EMS), which involves electromagnetic fields in the frequency range of 0–300 Hz, have been shown to reduce ischemic stroke volume by improving cerebral blood flow and recovery effects that are dependent on eNOS. Based on previous results, we herein explore the effects of ELF-EMS treatment (13.5 mT/10 and 60 Hz) on the activation of angiogenic processes in vitro in homeostatic conditions. Methods: Using human microvascular endothelial cells (HMEC-1), we studied cell proliferation, migration, and tube formation in vitro, as well as nitric oxide production and the effect of calcium and nitric oxide (NO) on these processes. Moreover, blood vessel formation was studied using a chicken chorioallantoic membrane (CAM) assay. Results: Our results showed that ELF-EMS increases proliferation, tube formation, and both the migration and transmigration of these cells, the latter of which was mediated via NO. In turn, calcium inhibition decreased ELF-EMF-induced NO production. Furthermore, ELF-EMS significantly increased blood vessel formation in the CAM assay. Conclusions: Our results indicated that ELF-EMS exposure (13.5 mT/10 and 60 Hz) significantly induces angiogenesis in vitro and in ovo, underscoring its potential application in the treatment of conditions characterized by insufficient blood supply.

Like women washing their laundry at the shore's lip, the geese groom themselves. Some slow. Others quick and jabbing.

Microglia perform surveillance and phagocytosis to maintain the homeostasis of the central nervous system (CNS). These processes are energetically demanding, and given the critical roles of mitochondria in providing ATP, the characteristics of the mitochondrial network can modulate microglial behavior. Although the Ca²⁺-permeable Transient Receptor Potential Vanilloid 4 (TRPV4) is known for regulating microglial morphology and migration, and it is implicated in mitochondrial calcium uptake, it is unknown whether TRPV4 affects the mitochondrial network in microglia. Our study provides evidence that TRPV4 plays a role in the integrity and complexity of the mitochondrial network in microglia. Quantification of the Mitochondrial Fragmentation and Complexity Index (MFCI) and increased pDrp1 (Ser616) showed a shift towards mitochondrial network fragmentation, and lowered complexity in Trpv4 knockout versus wild-type primary murine microglia in vitro. The distribution of mitochondria within microglia showed significant differences in density at 10–32 µm away from the nucleus. Furthermore, acute pharmacological TRPV4 inhibition with GSK2193874 did not induce significant mitochondria network fragmentation. Our findings establish TRPV4 as a regulator of mitochondrial dynamics and adaptive responses, highlighting its importance for maintaining homeostasis in microglia and the entire CNS.