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The pulsed ELF-MF stimulation system. Generator (a), coil (b), and the helmet (c) for the positioning of the coil.
Source publication
Extremely low frequency magnetic fields (ELF-MF) could be an alternative neuroprotective approach for ischemic stroke because preclinical studies have demonstrated their effects on the mechanisms underlying ischemic damage. The purpose of this open-label, one arm, dose-escalation, exploratory study is to evaluate the safety and tolerability of ELF-...
Context in source publication
Context 1
... in Capone et al. 11 . It consists of a custom-made rectangular, flexible coil kept in place by a Velcro strap, upon the ischemic hemisphere. The magnetic pulse generator (B-01; IGEA, Carpi, Italy) supplied the coil with a single-pulsed signal at 75 ± 2 Hz, with a pulse duration of 1.3 ms. The peak intensity of the magnetic field was 1.8 ± 0.2 mT (Fig. ...
Citations
... Currently, Li-TMS is used to explore its therapeutic effects in different psychiatric pathologies including TRD [38][39][40], anxiety [41][42], ASD [43], tinnitus [44], insomnia [45], and cerebrovascular events [46]. In the last decade, Li-TMS has gained particular interest due to the cellular effects this promotes in neurons. ...
Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation technique that induces action potentials in the stimulated cortical area and has been approved by the Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). The prevalence of MDD in Mexico almost tripled after the COVID-19 pandemic. In this study, we evaluated the safety and therapeutic effects of low-intensity TMS (Li-TMS) - characterized by inducing electric currents below the action potential threshold on the cerebral cortex - in 41 subjects diagnosed with treatment-resistant depression (TRD). A Li-TMS device dispensed repetitive magnetic pulses at 30 mT for 60 minutes during 20 sessions (once daily from Monday to Saturday) with the theta burst pattern. Our results suggest that Li-TMS is a safe therapy with antidepressant effects, demonstrated by the decrease in Beck Depression Inventory (BDI) scores and lessening of depressive symptoms.
... However, it is crucial for the exposure to the magnetic field to occur relatively soon after the ischemic episode to most efficiently enable such restoration. According to Capone et al., the action of ELF-MFs also increases the chances of survival for these cells, ensuring more effective neuroplasticity mechanisms, reduced neurological deficits and a faster return to functionality [20]. ...
... All of the remaining nine studies were included after reading the full-text manuscript ( Figure 1). Using the QATQS, only one study [24] was deemed to be "strong", the remaining eight studies [20,[25][26][27][28][29][30][31] were assessed as "weak". Detailed results of the methodological quality assessment for each study are presented in Figure 2. The results for individual sections among all studies showed that "selection bias" and "withdrawals and dropouts section" were assessed as the weakest while the "data collection methods" section was deemed the strongest. ...
... Eight studies [24][25][26][27][28][29][30][31] had a randomized controlled trial design with a sham intervention as the control group. One study [20] had two groups-a group exposed to shorter stimulation serving as the control group and a group exposed to longer stimulation. In seven studies, ELF-MFs were applied to the pelvic area [25][26][27][28][29][30][31], in one, head was exposed [20] and in one [24], Electromagnetic Network Targeting Field therapy exposing the entire brain and the cervical and upper thoracic portion of the spine was utilized; in this study, ELF-MF was performed with a device that was utilizing machine learning algorithms to identify spectral patterns characterizing motor functions within EEG measurements, collected during motor tasks. ...
Background: The aim of this study was to review the current state of scientific evidence on the effect of extremely low-frequency magnetic fields stimulation (ELF-MFs) on stroke patients. Methods: A systematic review of PubMed, ScienceDirect, PeDro and Embase databases was conducted. Only articles published in English, involving adult participants and focusing on individuals who had experienced a stroke, specifically examining the impact of ELF-MFs on post-stroke patients and had well-defined criteria for inclusion and exclusion of participants, were included. The methodological quality of the included studies was assessed using the Quality Assessment Tool for Quantitative Studies (QATQS). Results: A total of 71 studies were identified through database and reference lists’ search, from which 9 were included in the final synthesis. All included studies showed a beneficial effect of ELF-MFs on stroke patients, however seven of the included studies were carried by the same research group. Improvements were observed in domains such as oxidative stress, inflammation, ischemic lesion size, functional status, depressive symptoms and cognitive abilities. Conclusions: The available literature suggests a beneficial effect of ELF-MFs on post-stroke patients; however, the current data are too limited to broadly recommend the use of this method. Further research with improved methodological quality is necessary.
... Abbreviations: MADRS, Montgomery-Åsberg Depression Rating Scale; S.D., standard deviation. (Cañedo-Dorantes et al., 2015;Cichoń et al., 2017;Capone et al., 2017). ...
... Following the results of several in vivo and in vitro studies that showed the interaction between the low frequency (LF) and low energy (1 mT -3.5 mT) PEMFs with the A2a and A3 adenosine receptors [1], such signals have been investigated on humans as a possible neuroprotective tool, by carrying out an explorative open-label study to evaluate PEMFs safety and tolerability on 6 patients with acute ischemic stroke (i.e., within 48 hours from the insult) [2]. In this frame, a novel dosimetric methodology was assessed to attain, in a fast and reliable way a dose response curve that would help to correlate the exerted magnetic field intensity with possible observed effects on the ischemic lesion [3]. ...
... Among ELF-EMFs, low-frequency, low-energy PEMFs has been used as an effective, safe, and non-invasive technique in regenerative medicine to medicate several kinds of pain, such as post-operative pain (Hug and Röösli 2012;Osera et al. 2015), and in bone tissue engineering such as bone tissue repair and regeneration (Ceccarelli et al. 2013), in addition to its anti-inflammatory effects in several inflammatory disorders (Iwasa and Reddi 2018). It has also been shown that PEMFs exposure decreases hypoxia-induced cell death (Vincenzi et al. 2017;Gessi et al. 2019), reduces ischemic neuronal damage (Capone et al. 2017), enhances the antioxidant response (Falone et al. 2008(Falone et al. , 2016Osera et al. 2015) as well as activates the neurotrophic factors (Falone et al. 2008). Depending on the frequency, dose, exposure time, selected experimental cellular model, tissue or organism, ELF-EMFs have either cytotoxic or cytoprotective cellular effects (Akdağ et al. 2013;Vincenzi et al. 2013). ...
The low-frequency pulsed electromagnetic field (PEMF) may have possible cytoprotective effects against the destructive effects of oxidative stress. The goal was to investigate if shortterm low-frequency PEMF has cytoprotective effects in glioblastoma cell line following high-dose hydrogen peroxide (H2O2) treatment. U87-MG cells were divided into four groups: Sham-control group; PEMF group (cells exposed to PEMF); H2O2 group (cells treated with H2O2 at time intervals 30 min and 48 h, respectively); H2O2+PEMF group (cells exposed to PEMF after H2O2 treatment at time intervals 30 min and 48 h, respectively). The cell viability, levels of reactive oxygen species, glutathione peroxidase activity, and the amount of glutathione were measured. The cytoprotective effect of PEMF against deleterious effects of oxidative stress triggered by different time interval of H2O2 treatment might be mediated by the increase in the cell viability, the elevation in the antioxidant enzyme activity/amount, and the decrease in the reactive oxygen species level. In addition, the cytoprotective effect of PEMF varies depending on different time intervals of H2O2 treatment. In the light of these findings, further in vivo and/or in vitro studies on neurophysiological effects of PEMFs and their underlying molecular mechanisms are needed to elucidate neurotoxic or neuroprotective role against antioxidant defense mechanisms.
... The patients were treated for 5 consecutive days with pulsed ELF-EMS within 48 h after stroke onset. Overall, no adverse events or discomfort were reported both during treatment and during the 12-month follow-up phase (Capone et al., 2017). Only limited data are available on clinical trials that investigated the efficacy of ELF-EMS as ischemic stroke therapy. ...
Although spontaneous recovery can occur following ischemic stroke due to endogenous neuronal reorganization and neuroplastic events, the degree of functional improvement is highly variable, causing many patients to remain permanently impaired. In the last decades, non-invasive brain stimulation (NIBS) techniques have emerged as potential add-on interventions to the standard neurorehabilitation programs to improve post-stroke recovery. Due to their ability to modulate cortical excitability and to induce neuroreparative processes in the brain, multiple studies have assessed the safety, efficacy and (sub)cellular mechanisms of NIBS following ischemic stroke. In this review, an overview will be provided of the different NIBS techniques that are currently being investigated in (pre)clinical stroke studies. The NIBS therapies that will be discussed include transcranial magnetic stimulation, transcranial direct current stimulation and extremely low frequency electromagnetic stimulation. First, an overview will be given of the cellular mechanisms induced by NIBS that are associated with enhanced stroke outcome in preclinical models. Furthermore, the current knowledge on safety and efficacy of these NIBS techniques in stroke patients will be reviewed.
... Clinical studies reported in this field, such as preclinical studies, present a diversity of doses and treatments, but only PEMF has reached the clinical phase. Capone et al. (2017) performed a dose-escalation exploratory study to assess the effect of PEMF in acute ischemic stroke patients (within 48 h after the onset of the stroke). Eligible patients for the study were those older than 18 years, with first mono-hemispheric ischemic stroke, and National Institutes of Health Stroke Scale (NIHSS) score greater than 4. Exclusion criteria were acute intracranial hemorrhage; previous ischemic or hemorrhagic stroke; the history of seizure; contraindications to magnetic fields exposure life expectancy of fewer than 3 months, and other serious illness or complex disease that may confound treatment assessment. ...
... Parameters like respiratory and heart rate, blood pressure, pulse oximetry, and ECG signal were stable during EMF stimulation. It is important to mention that Capone et al. (2017) wanted to include a treatment of 240 min; however, no patient accepted this exposure time because it was considered too long and potentially interfering with the standard of care. This proves our previously mentioned concern on elevated exposure times in some treatments proposed in preclinical studies. ...
... In this case, Cichón et al. explained that exposure to the head of ELF-MF can affect the activation of the epileptic focus, but no reference to any study proving this is given by the authors. Moreover, Capone et al. performed an experiment to prove the safety of the ELF-MF showing that the treatment does not produce any side effect in humans when placed onto the skull (Capone et al., 2017). ...
Cerebral stroke is a leading cause of death and adult-acquired disability worldwide. To this date, treatment options are limited; hence, the search for new therapeutic approaches continues. Electromagnetic fields (EMFs) affect a wide variety of biological processes and accumulating evidence shows their potential as a treatment for ischemic stroke. Based on their characteristics, they can be divided into stationary, pulsed, and sinusoidal EMF. The aim of this review is to provide an extensive literature overview ranging from in vitro to even clinical studies within the field of ischemic stroke of all EMF types. A thorough comparison between EMF types and their effects is provided, as well as an overview of the signal pathways activated in cell types relevant for ischemic stroke such as neurons, microglia, astrocytes, and endothelial cells. We also discuss which steps have to be taken to improve their therapeutic efficacy in the frame of the clinical translation of this promising therapy.
... Using the PEMFs exposure system applied in preclinical studies (5)(6)(7)23,30) and in safety and tolerability studies on healthy volunteers (35), Capone et al. designed an open label, one arm, doseescalation exploratory study to evaluate the safety and tolerability of PEMFs in patients with acute ischemic stroke (clinicaltrials.gov NCT01941147) (43). PEMFs treatment (1.8 mT, 75 Hz) started within 48 hours from the stroke onset and was carried out for five consecutive days. ...
Objectives
Acute cerebral ischemia is characterized by several pathological processes evolving during time, which contribute to the final tissue damage. Secondary processes, such as prolonged inflammatory response, impaired mitochondrial function and oxidative stress, are responsible for the progression of brain injury to the peri-infarct area, called “penumbra.” Adenosine has been shown to play a crucial role in regulating the inflammatory cascade following brain ischemia. Pulsed electromagnetic fields (PEMFs) act as modulators of adenosine receptors, increasing the functionality of the endogenous adenosine. In particular, PEMF exposure induces a significant upregulation of A2A and A3 adenosine receptors in different neuronal cell types. Several lines of evidence suggest that PEMF exposure might play a neuroprotective role after ischemic damage.
Materials and Methods
This review summarizes the current knowledge on the mechanism of action of PEMFs and their biological effects on neuronal damage both in preclinical and clinical studies.
Results
PEMFs counteract hypoxia-induced apoptosis and ROS production in neuronal-like cells and exert a strong anti-inflammatory effect on microglial cells. Data from stroke animal models showed that PEMFs exposure is able to reduce the size of the infarct area and decrease the levels of pro-inflammatory mediators. In clinical studies, PEMFs stimulation proved to be safe and well tolerated. Preliminary results on acute ischemic stroke patients showed a dose-dependent reduction in the lesion size.
Conclusions
Altogether, these data demonstrate the efficacy of PEMFs against several mechanisms underlying ischemic damage and suggest that PEMFs might represent a novel noninvasive adjunctive treatment for acute ischemic stroke, providing neuroprotection and reducing functional deficits following ischemia.
... The figure-8 coil and circular coil parameters were referenced to model commercial coils (Wuhan Yiruide Medical Equipment New Technology Co., Ltd., Wuhan, China). A finite element method was used to solve the electromagnetic field distribution in the brain model (Capone et al., 2017;Samoudi et al., 2018). We set the permittivity and conductivity of the skull, dura mater, gray matter, white matter, cerebellum, spinal cord, cerebrospinal fluid and air at low frequencies separately. ...
Paired associative stimulation has been used in stroke patients as an innovative recovery treatment. However, the mechanisms underlying the therapeutic effectiveness of paired associative stimulation on neurological function remain unclear. In this study, rats were randomly divided into middle cerebral occlusion model (MCAO) and paired associated magnetic stimulation (PAMS) groups. The MCAO rat model was produced by middle cerebral artery embolization. The PAMS group received PAMS on days 3 to 20 post MCAO. The MCAO group received sham stimulation, three times every week. Within 18 days after ischemia, rats were subjected to behavioral experiments—the foot-fault test, the balance beam walking test, and the ladder walking test. Balance ability was improved on days 15 and 17, and the foot-fault rate was less in their affected limb on day 15 in the PAMS group compared with the MCAO group. Western blot assay showed that the expression levels of brain derived neurotrophic factor, glutamate receptor 2/3, postsynaptic density protein 95 and synapsin-1 were significantly increased in the PAMS group compared with the MCAO group in the ipsilateral sensorimotor cortex on day 21. Resting-state functional magnetic resonance imaging revealed that regional brain activities in the sensorimotor cortex were increased in the ipsilateral hemisphere, but decreased in the contralateral hemisphere on day 20. By finite element simulation, the electric field distribution showed a higher intensity, of approximately 0.4 A/m2, in the ischemic cortex compared with the contralateral cortex in the template. Together, our findings show that PAMS upregulates neuroplasticity-related proteins, increases regional brain activity, and promotes functional recovery in the affected sensorimotor cortex in the rat MCAO model. The experiments were approved by the Institutional Animal Care and Use Committee of Fudan University, China (approval No. 201802173S) on March 3, 2018.
... Emerging evidence indicates PEMFs as a potential strategy for ischemic stroke for their neuroprotective properties [7,8,27]. An open-label, one arm, dose-escalation, exploratory study has established the safety and tolerability of PEMFs in patients with acute ischemic stroke [28]. Recently, the mechanisms underlying PEMF-associated neuroprotective effects were deeply investigated in neuron-like cells [9,10] and microglial cells [11]. ...
Pulsed electromagnetic fields (PEMFs) are emerging as an innovative, non-invasive therapeutic option in different pathological conditions of the central nervous system, including cerebral ischemia. This study aimed to investigate the mechanism of action of PEMFs in an in vitro model of human astrocytes, which play a key role in the events that occur following ischemia. 1321N1 cells were exposed to PEMFs or hypoxic conditions and the release of relevant neurotrophic and angiogenic factors, such as VEGF, EPO, and TGF-β1, was evaluated by means of ELISA or AlphaLISA assays. The involvement of the transcription factor HIF-1α was studied by using the specific inhibitor chetomin and its expression was measured by flow cytometry. PEMF exposure induced a time-dependent, HIF-1α-independent release of VEGF from 1321N1 cells. Astrocyte conditioned medium derived from PEMF-exposed astrocytes significantly reduced the oxygen-glucose deprivation-induced cell proliferation and viability decrease in the neuron-like cells SH-SY5Y. These findings contribute to our understanding of PEMFs action in neuropathological conditions and further corroborate their therapeutic potential in cerebral ischemia.
