We developed a novel laparoscope-based electrosurgical RDN method for hypertension treatment. The feasibility of our system was confirmed through a simulation study as well as in vitro experiments. Our proposed method could be an effective treatment for resistant hypertension as well as central nervous system diseases.
Given its ability to modulate neuronal excitability, low-intensity magnetic stimulation (LIMS) has therapeutic potential in the treatment of neurological disorders. However, the underlying of LIMS effects remain poorly understood because LIMS does not directly generate action potentials. We aimed to elucidate these mechanisms by studying and systematically comparing the neurochemical changes induced in vitro by LIMS. To this end, we developed a simple in vitro magnetic stimulation device that allowed delivery of a range of stimulation parameters in order to generate sufficient field intensity for the subthreshold. In characterizing our custom-built system, we conducted computational simulations to determine the electromagnetic field exposure to a cell culture dish. Subsequently, using the custom-built LIMS system, we applied three different stimulation protocols to differentiated neuroblastoma cells for 30 min and then assessed the resultant neurochemical changes. We found that high-frequency (HF: 10 Hz) stimulation increased levels of the excitatory neurotransmitter, glutamate, while low-frequency (LF: 1 Hz) stimulation increased levels of the inhibitory neurotransmitter, GABA. These results suggest that LIMS effects are frequency-dependent: suppression of neuroexcitability occurs at LF and facilitation occurs at HF. Furthermore, we observed pattern-dependent changes when comparing repetitive high-frequency (rHF) and intermittent high-frequency (iHF) stimulations: iHF took more time to induce neurochemical change than rHF. In addition, we found that calcium changes were closely associated with glutamate changes in response to different stimulation parameters. Our experimental findings indicate that LIMS induces the release of neurotransmitters and affects neuronal excitability at magnetic field intensities far lower than suprathreshold, and that this in turn induces action potentials. Therefore, this study provides a cellular framework for understanding how low-intensity magnetic stimulation could affect clinical outcomes.
Tumor-treating fields (TTFields) are emerging cancer therapies based on alternating low-intensity electric fields that interfere with dividing cells and induce cancer cell apoptosis. However, to date, there is limited knowledge of their effects on normal cells, as well as the effects of different duty cycles on outcomes. The present study evaluated the effects of TTFields with different duty cycles on glioma spheroid cells and normal brain organoids. A customized TTFields system was developed to perform in vitro experiments with varying duty cycles. Three duty cycles were applied to three types of glioma spheroid cells and brain organoids. The efficacy and safety of the TTFields were evaluated by analyzing the cell cycle of glioma cells, and markers of neural stem cells (NSCs) and astrocytes in brain organoids. The application of the TTFields at the 75 and 100% duty cycle markedly inhibited the proliferation of the U87 and U373 compared with the control. FACS analysis revealed that the higher the duty cycle of the applied fields, the greater the increase in apoptosis detected. Exposure to a higher duty cycle resulted in a greater decrease in NSC markers and a greater increase in glial fibrillary acidic protein expression in normal brain organoids. These results suggest that TTFields at the 75 and 100% duty cycle induced cancer cell death, and that the neurotoxicity of the TTFields at 75% was less prominent than that at 100%. Although clinical studies with endpoints related to safety and efficacy need to be performed before this strategy may be adopted clinically, the findings of the present study provide meaningful evidence for the further advancement of TTFields in the treatment of various types of cancer.
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