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Drug treatment, electric stimulation and decimeter wave therapy have been shown to promote the repair and regeneration of the peripheral nerves at the injured site. This study prepared a Mackinnon's model of rat sciatic nerve compression. Electric stimulation was given immediately after neurolysis, and decimeter wave radiation was performed at 1 and 12 weeks post-operation. Histological observation revealed that intraoperative electric stimulation and decimeter wave therapy could improve the local blood circulation of repaired sites, alleviate hypoxia of compressed nerves, and lessen adhesion of compressed nerves, thereby decreasing the formation of new entrapments and enhancing compressed nerve regeneration through an improved microenvironment for regeneration. Immunohistochemical staining results revealed that intraoperative electric stimulation and decimeter wave could promote the expression of S-100 protein. Motor nerve conduction velocity and amplitude, the number and diameter of myelinated nerve fibers, and sciatic functional index were significantly increased in the treated rats. These results verified that intraoperative electric stimulation and decimeter wave therapy contributed to the regeneration and the recovery of the functions in the compressed nerves.
Electric stimulation therapy (EST) and magnetic sphincter augmentation (MSA) represent novel methods for the surgical treatment of gastroesophageal reflux disease (GERD). The aim of this review was to assess the effectiveness and safety of EST and magnetic sphincter augmentation device (MSAD) comapred to laparoscopic fundoplication (LF) and proton pump inhibitor therapy (in case of EST). We performed a systematic literature search without restrictions on publication dates in five electronic databases (MEDLINE, EMBASE, the Cochrane library, PubMed, and Centre for Reviews and Dissemination), complemented by hand search, search in trial registries, and documentation provided by the manufacturers. No study passed inclusion criteria for analyzing EST effectiveness. Concerning safety, lead erosion through the esophagus and trocar perforation of the small bowel occurred in 2.4% of patients (in one study). Only the registry study fulfilled inclusion criteria for effectiveness analysis of MSAD. The crucial outcome of GERD-health-related quality of life (HRQL) score improved from 20 to 3 points in MSAD patients, and from 23 to 3.5 points in LF patients. However, the LF patients were in a more severe stage of the disease. The results yield indefinite conclusions about the use of both MSAD and EST. Clinical effectiveness and safety of both MSAD and EST are not sufficiently proven and are yet to be supported by high quality evidence from randomized controlled trials.
Leishmaniasis is a neglected tropical disease with 1.6 million new cases reported each year. However, there are few safe, effective, and affordable treatments provided to those affected by this disease. Still under-appreciated as potential pharmaceutical targets, especially for cutaneous leishmaniasis infections, are the two isozymes of secreted acid phosphatase (SAP). These enzymes are involved in the survival of the parasite in the sand fly vector, and in infecting host macrophages. While the application of electric or electromagnetic fields as a medicinal therapeutic is not new, the utility of electric field application for the treatment of leishmaniasis is under studied. Studies involving the effects of electric fields on the cell secretion of SAP or the activity of SAP that has been secreted prior to electrical stimulation have not yet been reported. This work is the first report on the effect of specific electric fields on the activity of Leishmania tarentolae secreted acid phosphatases and the modulation of this secretion from the cells. In addition, the kinetic constants for the enzyme isoforms were determined as a function of days in culture and removal of carbohydrate from the glycosylated enzymes, while using a glycosidase, was shown to affect these kinetic constants.
Electroconvulsive therapy (ECT) remains the gold-standard treatment for patients with depressive episodes, but the underlying mechanisms for antidepressant response and procedure-induced cognitive side effects have yet to be elucidated. Such mechanisms may be complex and involve certain ECT parameters and brain regions. Regarding parameters, the electrode placement (right unilateral or bitemporal) determines the geometric shape of the electric field (E-field), and amplitude determines the E-field magnitude in select brain regions (e.g., hippocampus). Here, we aim to determine the relationships between hippocampal E-field strength, hippocampal neuroplasticity, and antidepressant and cognitive outcomes. We used hippocampal E-fields and volumes generated from a randomized clinical trial that compared right unilateral electrode placement with different pulse amplitudes (600, 700, and 800 mA). Hippocampal E-field strength was variable but increased with each amplitude arm. We demonstrated a linear relationship between right hippocampal E-field and right hippocampal neuroplasticity. Right hippocampal neuroplasticity mediated right hippocampal E-field and antidepressant outcomes. In contrast, right hippocampal E-field was directly related to cognitive outcomes as measured by phonemic fluency. We used receiver operating characteristic curves to determine that the maximal right hippocampal E-field associated with cognitive safety was 112.5 V/m. Right hippocampal E-field strength was related to the whole-brain ratio of E-field strength per unit of stimulation current, but this whole-brain ratio was unrelated to antidepressant or cognitive outcomes. We discuss the implications of optimal hippocampal E-field dosing to maximize antidepressant outcomes and cognitive safety with individualized amplitudes.
By enhancing vagal activity, auricle transcutaneous electric nerve stimulation (TENS) is developed as a non-invasive therapy for heart failure. Nevertheless, though shoulder TENS used for treating adhesive capsulitis could affect vagal tone, its potential impact on heart functions remains unclear. In this study, electrocardiogram (ECG) and heart rate (HR) of subjects in response to sham, right-sided, or left-sided shoulder TENS (TENS-S, TENS-R, and TENS-L, respectively; 5 min) were recorded and analyzed. During the stimulation period, TENS-R constantly and TENS-L transiently decreased the HR of subjects; both TENS-R and TENS-L increased powers of the low- and high-frequency spectra. While TENS-R exhibiting no effect, TENS-L increased the ratio of low/high-frequency power spectrum indicating TENS-R decreased the HR through potentiating cardiac vagal tone. Collectively, these results suggest TENS could be an early and non-invasive therapy for heart failure patients before considering implant devices or devices are not feasible; moreover, therapists/physicians need to carefully monitor the potential adverse events during treatment for patient safety.Trial registration: The study protocol was registered in ClinicalTrials.gov (NCT03982472; 11/06/2019).
Electroconvulsive therapy (ECT) has known beneficial effects on the core motor symptoms of Parkinson's disease (PD), likely through induction of dopamine release and sensitivity of dopamine receptors. Mesenchymal stem cells (MSCs) can salvage loss of dopamine in PD through their differentiation into dopaminergic neurons. However, it is not known if combined ECT and MSC transplantation may have a synergistic effect against PD. Here, we showed that ECT significantly increased the differentiation of the transplanted MSCs into dopaminergic neurons in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. On the other hand, transplantation of MSCs significantly increased dopamine levels after ECT. Co-application of ECT and MSC transplantation generated a synergistic effect through increases in dopamine and decreases in pro-inflammatory cytokines, resulting in significantly attenuated defect in stepping test and rotational behavior in MPTP-mice. Together, our data suggest that combined ECT and MSC transplantation can be a valuable treatment of PD.
The central nervous system (CNS) is highly vascularized where neuronal cells are located in proximity to endothelial cells, astroglial limitans, and neuronal processes constituting integrated neurovascular units. In contrast to many other organs, the CNS has a blood-brain barrier (BBB), which becomes compromised due to infection, neuroinflammation, neurodegeneration, traumatic brain injury, and other reasons. BBB disruption is presumably involved in neuronal injury during epilepsy and psychiatric disorders. Therefore, many types of neuropsychological disorders are accompanied by an increase in BBB permeability leading to direct contact of circulating blood cells in the capillaries with neuronal cells in the CNS. The second most abundant type of blood cells are platelets, which come after erythrocytes and outnumber ~100-fold circulating leukocytes. When BBB becomes compromised, platelets swiftly respond to the vascular injury and become engaged in thrombosis and hemostasis. However, more recent studies demonstrated that platelets could also enter CNS parenchyma and directly interact with neuronal cells. Within CNS, platelets become activated by recognizing major brain gangliosides on the surface of astrocytes and neurons and releasing a milieu of pro-inflammatory mediators, neurotrophic factors, and neurotransmitters. Platelet-derived factors directly stimulate neuronal electric and synaptic activity and promote the formation of new synapses and axonal regrowth near the site of damage. Despite such active involvement in response to CNS damage, the role of platelets in neurological disorders was not extensively studied, which will be the focus of this review.
The major aim of stroke therapies is to stimulate brain repair and to improve behavioral recuperation after cerebral ischemia. Despite remarkable advances in cell therapy for stroke, stem cell-based tissue replacement has not been achieved yet stimulating the search for alternative strategies for brain self-repair using the neurogenic zones of the brain, the dentate gyrus and the subventricular zone (SVZ). However, during aging, the potential of the hippocampus and the SVZ to generate new neuronal precursors, declines. We hypothesized that electrically stimulation of endogenous neurogenesis in aged rats could increase the odds of brain self-repair and improve behavioral recuperation after focal ischemia. Following stroke in aged animals, the rats were subjected to two sessions of electrical non-convulsive stimulation using ear-clip electrodes, at 7- and 24 days after MCAO. Animal were sacrificed after 48 days. We report that electrical stimulation (ES) stimulation of post-stroke aged rats led to an improved functional recovery of spatial long-term memory (T-maze) but not on the rotating pole or the inclined plane, both tests requiring complex sensorimotor skills. Surprisingly, ES had a detrimental effect on the asymmetric sensorimotor deficit. Histologically, there was a robust increase in the number of doublecortin-positive cells in the dentate gyrus and SVZ of the infarcted hemisphere and the presence of a considerable number of neurons expressing tubulin beta III in the infarcted area. Among the gene that were unique to ES, we noted increases in the expression of seizure related 6 homolog like which is one of the physiological substrate of the β-secretase BACE1 involved in the pathophysiology of the Alzheimer's disease and Igfbp3 and BDNF receptor mRNAs which has been shown to have a neuroprotective effect after cerebral ischemia. However, ES was associated with a long-term down regulation of cortical gene expression after stroke in aged rats suggesting that gene expression in the peri-infarcted cortical area may not be related to electrical stimulation induced-neurogenesis in the subventricular zone and hippocampus.
Background and Objectives: An altered sympathetic function is established in primary arterial hypertension (PAH) development. Therefore, PAH could be targeted by applying an electric current to the medulla where reflex centers for blood pressure control reside. This study aims to evaluate the electric caudal ventrolateral medulla (CVLM) stimulation effect on blood pressure and animal survivability in a freely moving rat model. Materials and Methods: A total of 20 Wistar rats aged 12-16 weeks were randomly assigned to either: the experimental group (n = 10; electrode tip implanted in CVLM region) or the control group (n = 10; tip implanted 4 mm above the CVLM in the cerebellum). After a period of recovery (4 days), an experimental phase ensued, divided into an "OFF stimulation" period (5-7 days post-surgery) and an "ON stimulation" period (8-14 days post-surgery). Results: Three animals (15%, one in the control, two in the experimental group) dropped out due to postoperative complications. Arterial pressure in the experimental group rats during the "OFF stimulation" period decreased by 8.23 mm Hg (p = 0.001) and heart rate by 26.93 beats/min (p = 0.008). Conclusions: From a physiological perspective, CVLM could be an effective deep brain stimulation (DBS) target for drug-resistant hypertension: able to influence the baroreflex arc directly, having no known direct integrative or neuroendocrine function. Targeting the baroreflex regulatory center, but not its sensory or effector parts, could lead to a more predictable effect and stability of the control system. Although targeting neural centers in the medullary region is considered dangerous and prone to complications, it could open a new vista for deep brain stimulation therapy. A possible change in electrode design would be required to apply CVLM DBS in clinical trials in the future.
Deep brain stimulation (DBS) is a surgical therapy to alleviate symptoms of certain brain disorders by electrically modulating neural tissues. Computational models predicting electric fields and volumes of tissue activated are key for efficient parameter tuning and network analysis. Currently, we lack efficient and flexible software implementations supporting complex electrode geometries and stimulation settings. Available tools are either too slow (e.g. finite element method-FEM), or too simple, with limited applicability to basic use-cases. This paper introduces FastField, an efficient open-source toolbox for DBS electric field and VTA approximations. It computes scalable electric field approximations based on the principle of superposition, and VTA activation models from pulse width and axon diameter. In benchmarks and case studies, FastField is solved in about 0.2 s, ~ 1000 times faster than using FEM. Moreover, it is almost as accurate as using FEM: average Dice overlap of 92%, which is around typical noise levels found in clinical data. Hence, FastField has the potential to foster efficient optimization studies and to support clinical applications.
Capacitive Resistive Electric Transfer (CRET) therapy applies currents of 0.4-0.6 MHz to treatment of inflammatory and musculoskeletal injuries. Previous studies have shown that intermittent exposure to CRET currents at subthermal doses exert cytotoxic or antiproliferative effects in human neuroblastoma or hepatocarcinoma cells, respectively. It has been proposed that such effects would be mediated by cell cycle arrest and by changes in the expression of cyclins and cyclin-dependent kinase inhibitors. The present work focuses on the study of the molecular mechanisms involved in CRET-induced cytostasis and investigates the possibility that the cellular response to the treatment extends to other phenomena, including induction of apoptosis and/or of changes in the differentiation stage of hepatocarcinoma cells. The obtained results show that the reported antiproliferative action of intermittent stimulation (5 m On/4 h Off) with 0.57 MHz, sine wave signal at a current density of 50 µA/mm(2), could be mediated by significant increase of the apoptotic rate as well as significant changes in the expression of proteins p53 and Bcl-2. The results also revealed a significantly decreased expression of alpha-fetoprotein in the treated samples, which, together with an increased concentration of albumin released into the medium by the stimulated cells, can be interpreted as evidence of a transient cytodifferentiating response elicited by the current. The fact that this type of electrical stimulation is capable of promoting both, differentiation and cell cycle arrest in human cancer cells, is of potential interest for a possible extension of the applications of CRET therapy towards the field of oncology.
The 448 kHz capacitive‑resistive electric transfer (CRET) is an electrothermal therapy currently applied in anticellulite and antiobesity treatments. The aim of the present study was to determine whether exposure to the CRET electric signal at subthermal doses affected early adipogenic processes in adipose‑derived stem cells (ADSC) from human donors. ADSC were incubated for 2 or 9 days in the presence of adipogenic medium, and exposed or sham‑exposed to 5 min pulses of 448 kHz electric signal at 50 µA/mm2 during the last 48 h of the incubation. Colorimetric, immunofluorescence, western blotting and reverse transcription‑quantitative polymerase chain reaction assays were performed to assess adipogenic differentiation of the ADSC. Electric stimulation significantly decreased cytoplasmic lipid content, after both 2 and 9 days of differentiation. The antiadipogenic response in the 9 day samples was accompanied by activation of mitogen‑activated protein kinase kinase 1/2, decreased expression and partial inactivation of peroxisome proliferator‑activated receptor (PPAR) γ, which was translocated from the nucleus to the cytoplasm, together with a significant decrease in the expression levels of the PPARG1 gene, perilipin, angiopoietin‑like protein 4 and fatty acid synthase. These results demonstrated that subthermal stimulation with CRET interferes with the early adipogenic differentiation in ADSC, indicating that the electric stimulus itself can modulate processes controlling the synthesis and mobilization of fat, even in the absence of the concomitant thermal and mechanical components of the thermoelectric therapy CRET.
The clinical effect of electroconvulsive therapy (ECT) is mediated by eliciting a generalized seizure, which is achieved by applying electrical current to the head via scalp electrodes. The anatomy of the head influences the distribution of current flow in each brain region. Here, we investigated whether individual differences in simulated local electrical field strength are associated with ECT efficacy. We modeled the electric field of 67 depressed patients receiving ECT. Patient's T1 magnetic resonance images were segmented, conductivities were assigned to each tissue and the finite element method was used to solve for the electric field induced by the electrodes. We investigated the correlation between modelled electric field and ECT outcome using voxel-wise general linear models. The difference between bilateral (BL) and right unilateral (RUL) electrode placement was striking. Even within electrode configuration, there was substantial variability between patients. For the modeled BL placement, stronger electric field strengths appeared in the left hemisphere and part of the right temporal lobe. Importantly, a stronger electric field in the temporal lobes was associated with less optimal ECT response in patients treated with BL-ECT. No significant differences in electric field distributions were found between responders and non-responders to RUL-ECT. These results suggest that overstimulation of the temporal lobes during BL stimulation has negative consequences on treatment outcome. If replicated, individualized pre-ECT computer-modelled electric field distributions may inform the development of patient-specific ECT protocols.
There has been increasing interest in the use of loud acoustic stimulation (LAS) to gain insight into the preparation and initiation of motor actions. Typically, LAS presented during movement preparation in healthy participants culminates in the earlier than normal initiation of the prepared movement and an increase in the magnitude of the response. Recent reports have shown LAS can also facilitate movement in chronic stroke survivors. This suggests that current therapies for motor recovery after stroke might benefit from employing such alternate methods of triggering movement. In this study we sought to test a new way to facilitate motor actions that could be of relevance in clinical settings. Five individuals with chronic motor impairments due to stroke and eight healthy young adults performed a functional reaching task in response to a visual go-signal. On 30% of the trials, LAS or electric stimuli (collectively, sensory stimuli) were unexpectedly presented in synchrony with the go-signal. Both healthy and stroke participants reacted with shorter latencies and executed faster responses when sensory stimulation was synchronized with the go-signal. We have replicated previous findings showing acoustic stimuli can aid movement execution in chronic stroke survivors and demonstrated the same type of effect can be achieved using electric stimulation. Thus, these two types of sensory stimuli can be easily integrated with current devices available to assist people with stroke to engage in rehabilitation efforts.
Neural progenitor cells (NPCs) have been shown to serve as an efficient therapeutic strategy in different cell therapy approaches, including spinal cord injury treatment. Despite the reported beneficial effects of NPC transplantation, the low survival and differentiation rates constrain important limitations. Herein, a new methodology has been developed to overcome both limitations by applying a combination of wireless electrical and magnetic stimulation to NPCs seeded on aligned poly(lactic acid) nanofibrous scaffolds for in vitro cell conditioning prior transplantation. Two stimulation patterns were tested and compared, continuous (long stimulus applied once a day) and intermittent (short stimulus applied three times a day). The results show that applied continuous stimulation promotes NPC proliferation and preferential differentiation into oligodendrocytic and neuronal lineages. A neural-like phenotypic induction was observed when compared to unstimulated NPCs. In contrast, intermittent stimulation patterns did not affect NPC proliferation and differentiation to oligodendrocytes or astrocytes morphology with a detrimental effect on neuronal differentiation. This study provides a new approach of using a combination of electric and magnetic stimulation to induce proliferation and further neuronal differentiation, which would improve therapy outcomes in disorders such as spinal cord injury.
At present, drug therapy for diarrhea-predominant irritable bowel syndrome (IBS-D) has made great progress; however, it does not often produce a satisfying curative effect. Transcutaneous electric nerve stimulation over acupoints (Acu-TENS) might be more effective in improving patient's symptoms and producing fewer side-effects as a result.Although with a great progress of the drug therapy for IBS-D, it is often hard to achieve its satisfactory curative effect. Acu-TENS that may be effective to improve patients' symptoms and fewer side-effects will be sought. There is no systematic review concerning the efficacy of Acu-TENS for IBS-D published. Therefore, this review aims to systematically evaluate the efficacy of Acu-TENS on IBS-D.
Deep brain stimulation (DBS) is being investigated as a treatment for therapy-refractory obsessive compulsive disorder (OCD). Many different brain targets are being trialled. Several of these targets such as the ventral striatum (including the nucleus accumbens (NAc)), the ventral capsule, the inferior thalamic peduncle, and the bed nucleus of stria terminalis (BNST)) belong to the same network, are anatomically very close to one another, or even overlap. Data is still missing on how various stimulation parameters in a given target will affect surrounding anatomical areas and impact the clinical outcome of DBS.
Neural stem cells (NSCs) are considered as candidates for cell replacement therapy in many neurological disorders. However, the propensity for their differentiation to proceed more glial rather than neuronal phenotypes in pathological conditions limits positive outcomes of reparative transplantation. Exogenous physical stimulation to favor the neuronal differentiation of NSCs without extra chemical side effect could alleviate the problem, providing a safe and highly efficient cell therapy to accelerate neurological recovery following neuronal injuries.
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