Effects Of Long-term Electrical Stimulation Research Articles

Effect of Electrical Stimulation on Diabetic Human Skin Fibroblast Growth and the Secretion of Cytokines and Growth Factors Involved in Wound Healing.

Simple SummaryWith the number of diabetic patients on the rise, diabetes has become a major health issue affecting millions of people worldwide. One complication of diabetes is foot ulcers, which are difficult to repair and are thus associated with major clinical problems that may lead to foot amputation and even patient death. The delayed repair of diabetic foot ulcers is due to the slow growth of one of the cell types involved in wound healing, namely, fibroblasts. Fibroblasts inhabit deep skin tissue. Post-wound, they grow and produce skin tissues to enable other cells to close the wound. Even though normal fibroblast growth can be increased by electrical stimulation, it is not clear whether diabetic fibroblast also responds to electrical stimulation. We demonstrated for the first time that a weak direct current electrical field increased diabetic fibroblast growth. The use of electrical stimulation could thus potentially help heal diabetic foot ulcers and ultimately improve patient health and well-being.Diabetic foot ulcers are indicative of an impaired wound healing process. This delay may be resolved through electrical stimulation (ES). The goal of the present study was to evaluate the effect of ES on diabetic fibroblast adhesion and growth, and the secretion of cytokines and growth factors. Diabetic human skin fibroblasts (DHSF) were exposed to various intensities of direct current ES (100, 80, 40 and 20 mV/mm). The effect of ES on fibroblast adhesion and growth was evaluated using Hoechst staining, MTT and trypan blue exclusion assays. The secretion of cytokine and growth factor was assessed by cytokine array and ELISA assay. The long-term effects of ES on DHSF shape and growth were determined by optical microscopy and cell count. We demonstrated that ES at 20 and 40 mV/mm promoted cell adhesion, viability and growth. ES also decreased the secretion of pro-inflammatory cytokines IL-6 and IL-8 yet promoted growth factor FGF7 secretion during 48 h post-ES. Finally, the beneficial effect of ES on fibroblast growth was maintained up to 5 days post-ES. Overall results suggest the possible use of low-intensity direct current ES to promote wound healing in diabetic patients.

Electrical stimulation of referred sensation area alleviates phantom limb pain.

Patients with brachial plexus avulsion (BPA) usually experience phantom sensations and phantom limb pain (PLP) in the deafferented limb. It has been suggested that evoking the sensation of touch in the deafferented limb by stimulating referred sensation areas (RSAs) on the cheek or shoulder might alleviate PLP. However, feasible rehabilitation techniques using this approach have not been reported. The present study sought to examine the analgesic effects of simple electrical stimulation of RSAs in BPA patients with PLP. Study 1: Electrical stimulation of RSAs for 60 minutes was conducted for six BPA patients suffering from PLP to examine short-term analgesic effects. Study 2: A single case design experiment was conducted with two BPA patients to investigate whether electrical stimulation of RSAs was more effective for alleviating PLP than control electrical stimulation (electrical stimulation of sites on side opposite to the RSAs), and to elucidate the long-term effects of electrical stimulation of RSAs. Study 1: Electrical stimulation of RSAs evoked phantom touch sensations in the deafferented limb, and significantly alleviated PLP (p < 0.05). Study 2: PLP was alleviated more after electrical stimulation on RSAs compared with control electrical stimulation (p < 0.05). However, the analgesic effects of electrical stimulation on RSAs were observed only in the short term, not in the long term (p > 0.05). Electrical stimulation of RSAs not only evoked phantom touch sensation but also alleviated PLP in the short term. The results indicate that electrical stimulation of RSAs may provide a useful practical rehabilitation technique for PLP. Future studies will be required to clarify the mechanisms underlying immediate PLP alleviation via electrical stimulation of RSAs.

Effects of Electrical Stimulation in Tinnitus Patients: Conventional Versus High-Definition tDCS

Background. Contradictory results have been reported for transcranial direct current stimulation (tDCS) as treatment for tinnitus. The recently developed high-definition tDCS (HD tDCS) uses smaller electrodes to limit the excitation to the desired brain areas. Objective. The current study consisted of a retrospective part and a prospective part, aiming to compare 2 tDCS electrode placements and to explore effects of HD tDCS by matched pairs analyses. Methods. Two groups of 39 patients received tDCS of the dorsolateral prefrontal cortex (DLPFC) or tDCS of the right supraorbital–left temporal area (RSO-LTA). Therapeutic effects were assessed with the tinnitus functional index (TFI), a visual analogue scale (VAS) for tinnitus loudness, and the hyperacusis questionnaire (HQ) filled out at 3 visits: pretherapy, posttherapy, and follow-up. With a new group of patients and in a similar way, the effects of HD tDCS of the right DLPFC were assessed, with the tinnitus questionnaire (TQ) and the hospital anxiety and depression scale (HADS) added. Results. TFI total scores improved significantly after both tDCS and HD tDCS (DLPFC: P < .01; RSO-LTA: P < .01; HD tDCS: P = .05). In 32% of the patients, we observed a clinically significant improvement in TFI. The 2 tDCS groups and the HD tDCS group showed no differences on the evolution of outcomes over time (TFI: P = .16; HQ: P = .85; VAS: P = .20). Conclusions. TDCS and HD tDCS resulted in a clinically significant improvement in TFI in 32% of the patients, with the 3 stimulation positions having similar results. Future research should focus on long-term effects of electrical stimulation.

Implantable liquid metal-based flexible neural microelectrode array and its application in recovering animal locomotion functions

With significant advantages in rapidly restoring the nerve function, electrical stimulation of nervous tissue is a crucial treatment of peripheral nerve injuries leading to common movement disorder. However, the currently available stimulating electrodes generally based on rigid conductive materials would cause a potential mechanical mismatch with soft neural tissues which thus reduces long-term effects of electrical stimulation. Here, we proposed and fabricated a flexible neural microelectrode array system based on the liquid metal GaIn alloy (75.5% Ga and 24.5% In by weight) and via printing approach. Such an alloy with a unique low melting point (10.35 °C) owns excellent electrical conductivity and high compliance, which are beneficial to serve as implantable flexible neural electrodes. The flexible neural microelectrode array embeds four liquid metal electrodes and stretchable interconnects in a PDMS membrane (500 µm in thickness) that possess a lower elastic modulus (1.055 MPa), which is similar to neural tissues with elastic moduli in the 0.1–1.5 MPa range. The electrical experiments indicate that the liquid metal interconnects could sustain over 7000 mechanical stretch cycles with resistance approximately staying at 4 Ω. Over the conceptual experiments on animal sciatic nerve electrical stimulation, the dead bullfrog implanted with flexible neural microelectrode array could even rhythmically contract and move its lower limbs under the electrical stimulations from the implant. This demonstrates a highly efficient way for quickly recovering biological nerve functions. Further, the good biocompatibility of the liquid metal material was justified via a series of biological experiments. This liquid metal modality for neural stimulation is expected to play important roles as biologic electrodes to overcome the fundamental mismatch in mechanics between biological tissues and electronic devices in the coming time.

Effects of Electrical Stimulation on Risk Factors for Developing Pressure Ulcers in People with a Spinal Cord Injury: A Focused Review of Literature.

Pressure ulcers (PUs) are a common and serious problem for wheelchair users, such as individuals with a spinal cord injury (SCI), resulting in great discomfort, loss of quality of life, and significant medical care costs. Therefore, it is of utmost importance to prevent PUs. In this literature overview, the effects of electrical stimulation (ES) on the risk factors for developing PUs in people with an SCI are examined and synthesized from January 1980 to January 2015. Thirty-four relevant studies of PU prevention in SCI were identified. Four were randomized clinical trials, 24 were case series, 6 had other designs. Three types of ES modalities were identified. The methodological quality varied from poor to fairly strong, with a large variety in used ES parameters. Twenty-three studies were identified describing short-term effects of ES on interface pressure, oxygenation, and/or blood flow, and 24 studies described the long-term effects of ES on muscle volume, muscle strength, and histology. Whereas there is a lack of controlled studies on the effects of ES on PU incidence, which disallows definite conclusions, there is moderate evidence to suggest that ES-induced muscle activation has a positive influence on several risk factors for developing PUs in people with an SCI.

Soft Graphene Nanofibers Designed for the Acceleration of Nerve Growth and Development.

Soft graphene nanofibers with recoverable electrical conductivity and excellent physicochemical stability are prepared by a controlled assembly technique. By using the soft graphene nanofibers for cellular electrical stimulation, the common inhibitory effect of long-term electrical stimulation on nerve growth and development is avoided, which usually happens with traditional 2D conductive materials.

Short‐term and Long‐term Effects of Electrical Stimulation on Skin Properties

Electrical stimulation (ES) has been used in treating different medical conditions; however, not much is known about the effect of this application on skin properties. The purpose of this study was to investigate the short-term and long-term effects of ES on biophysical properties of the skin. A pretest-posttest control design was used in the study. Thirteen men (N = 13, age (M ± SD), 19 ± 5.6 years) were free of skin abnormality on the volar aspect of both forearms. Four areas were allocated and marked with a layout template of two circles 2 cm in diameter and 2 cm apart. Areas 1 and 2 were allocated on the experimental forearm and area 3 and 4 on the control forearm. ES was applied for 15 minutes with two rubber electrodes 8 cm apart surrounding areas 1 and 2 on the experimental forearm three times a week for 2 weeks. Skin properties including transepidermal water loss (TEWL), melanin content, erythema, elasticity and pH were measured pre-ES, during ES and post-ES, and after 2 weeks of applying ES to find out the short-term and long-term effects on skin. The TEWL was increased during ES at 7, 15 and 15-minutes post-ES compared with the baseline (p < 0.01) and to the control forearm (p = 0.04) measurements, and no increase have been noticed of TEWL on the control forearm (p = 0.11). Also, we found no difference in the other skin properties (p > 0.05) on both forearms, and there were no long-term effects (p > 0.05) in any tested variable. Electrical stimulation caused temporary increase in TEWL with no effects on other skin properties.

Auditory Brainstem Implant in Prelingually Deaf Children

Introduction: Auditory brainstem implant (ABI) has been placed in children who are born deaf due to cochlear nerve aplasia or with a severe degree of inner ear dysplasia, and for whom a cochlear implant is not an option. Application of ABI is more complicated than cochlear implant because ABI electrodes are placed in the cochlear nucleus, which is near some important cranial nerves. Electrical stimulation of the cochlear nucleus has some risks. When fitting the ABI, it is also important to decide which electrodes have effective auditory stimulation and which electrodes have side effects and must be closed. In children with cochlear nerve aplasia or inner ear dysplasia, there are risks and limitations because of the size and shape of the cochlear nucleus. We do not have information on the effects of long-term electrical stimulation of the cochlear nucleus in children.

On the effect of long-term electrical stimulation on three-dimensional cell cultures: Hen embryo brain spheroids

A comprehensive dataset of multielectrode array recordings was collected from three-dimensional hen embryo brain cell cultures, termed spheroids, under long-term electrical stimulation. The aim is to understand the ongoing changes in the spiking activity under electrical stimulation within the lifetime of 14-72DIV of the neuronal networks contained therein. The spiking dynamics were analyzed and behavioral characteristics derived. Some effects on spiking patterns and exhaustion were followed in culture lifetime. With respect to the culture development, two main types of spiking exhaustion were found: one which materializes in the form of a drop in the sporadic (tonic) spiking frequency at the later maturation stages; and another associated with decreasing spiking train appearance throughout an experimental period.

Effect of long-term electrical stimulation on motor recovery and improvement of clinical residuals in patients with unresolved facial nerve palsy

Purpose: This study investigated the efficacy of a pulsatile electrical current to shorten neuromuscular conduction latencies and minimize clinical residuals in patients with chronic facial nerve damage caused by Bell’s palsy or acoustic neuroma excision. Subjects: The study group included 12 patients (mean age 50.4 ± 12.3 years) with idiopathic Bell’s palsy and 5 patients (mean age 45.6 ± 10.7 years) whose facial nerves were surgically sacrificed. The mean time since the onset of paresis/paralysis was 3.7 years (range 1-7 years) and 7.2 years (range 6-9 years) for the Bell’s and neuroma excision groups, respectively. Method And Procedures: Motor nerve conduction latencies, House-Brackmann facial recovery scores, and a 12-item clinical assessment of residuals were obtained 3 months before the onset of treatment, at the beginning of treatment, and after 6 months of stimulation. Patients were treated at home for periods of up to 6 hours daily for 6 months with a battery-powered stimulator. Stimulation intensity was kept at a submotor level throughout the study. Surface electrodes were secured over the most affected muscles. Groups and time factors were used in the analyses of the 3 outcome measures. Results: No statistical differences were found between the two diagnostic groups with respect to any of the 3 outcome measures. Mean motor nerve latencies decreased by 1.13 ms (analysis of variance test, significant P = 0.0001). House-Brackmann scores were also significantly lower (Wilcoxon signed rank test, P = 0.0003) after treatment. Collective scores on the 12 clinical impairment measures decreased 28.7 ± 8.1 points after 6 months [analysis of variance test, significant P = 0.0005). Eight patients showed more than 40% improvement, 4 better than 30%, and 5 less than 10% improvement in residuals score. Conclusion: These data are consistent with the notion that long-term electrical stimulation may facilitate partial reinnervation in patients with chronic facial paresis/paralysis. Additionally, residual clinical impairments are likely to improve even if motor recovery is not evident. (Otolaryngol Head Neck Surg 2000;122:246-52.)

Cochlear pathology following chronic electrical stimulation of the auditory nerve: II deafened kittens

The present study examines the effects of long-term electrical stimulation of the auditory nerve on cochlear histopathology and spiral ganglion cell survival in young sensorineural deafened cats. Eight kittens were deafened using kanamycin and ethacrynic acid, and implanted with bipolar or monopolar scala tympani electrodes. Following recovery from surgery the animals were unilaterally stimulated using charge balanced biphasic current pulses for 450–1730 hours over implant periods of up to four months. Charge densities varied from 0.6–0.9 μC.cm −2 geom. per phase for monopolar electrodes to 12–26 μC.cm −2 geom. per phase for the bipolar electrodes. Electrically-evoked auditory brainstem responses (EABRs) were periodically monitored during stimulation to confirm that the stimulus levels were above threshold, and to monitor any change in the response of the auditory nerve. Following completion of the stimulation program cochleae were prepared for histological examination. EABRs exhibited relatively stable thresholds for both stimulated and implanted, unstimulated control cochleae for the stimulus duration. While the growth in response amplitude as a function of stimulus current remained stable for the bipolar control and monopolar stimulated cochleae, the five cochleae chronically stimulated using bipolar electrodes exhibited a moderate to large increase in response amplitude. These increases were associated with a more widespread fibrous tissue response which may have altered the current distribution within these cochleae. Implanted control cochleae exhibited significantly less tissue response within the scala tympani. Importantly, we observed no statistically significant difference in the spiral ganglion cell density associated with chronic electrical stimulation when compared with unstimulated control cochleae. While the present study supports the safe application of cochlear implants in young profoundly deafened children, it does not corroborate previous studies that have reported electrical stimulation providing a trophic effect on degenerating auditory nerve fibres.

Effect of long-term electrical stimulation on vascular supply and fatigue in chronically ischemic muscles.

Fast skeletal muscles of Sprague-Dawley rats [tibialis anterior (TA) and extensor digitorum longus (EDL)] were subjected to ischemia by unilateral ligation of the common iliac artery. In some animals, ischemia was combined with indirect electrical stimulation at 10 Hz either for 3 x 2 h (strenuous activity) or for 7 x 10-min bouts/day (mild activity). After 2 wk, muscle blood flow and fatigue were measured during 5-min isometric supramaximal twitch contractions at 4 Hz. Terminal arteriole diameters were assessed in TA by intravital microscopy at rest and during contractions. Vascular perfusion pressure in the muscles was estimated from measurements in the carotid and saphenous arteries below the site of ligation. Capillary supply was expressed in TA and EDL as capillary-to-fiber ratio on the basis of histochemical staining for capillaries. Strenuous stimulation of ischemic muscles increased their atrophy, failed to restore blood flow, and actually worsened fatigue. In contrast, mild stimulation improved perfusion pressure, increased capillary-to-fiber ratio in the glycolytic part of TA, restored dilatation of terminal arterioles during muscle contractions, and improved blood flow and muscle fatigue so that they were no longer significantly different from control muscles. Thus, an attenuated intermittent protocol may be indicated in the treatment of muscle ischemia.

Effects of vagal nerve stimulation on laryngeal function

Functional electrical stimulation is a developing methodology that shows significant potential in the management of peripheral neuromuscular deficits. Potential applications in the head and neck area, including control of bilateral vocal fold paralysis and spasmodic dysphonia, have recently been explored. Despite promising early results, very little is known about the mechanisms of action or the long-term effects of electrical stimulation on human laryngeal function. Recent development of implantable vagal nerve stimulators as a method to control intractable seizures in individuals who have not responded to medication provides a unique opportunity to study its effect on the normal human larynx. Laryngeal and vocal function testing was studied on five individuals who had undergone vagal nerve stimulator implants for intractable seizures. Consistent abduction/adduction of the left vocal fold was achieved at 20 and 40 Hz, respectively. Higher levels of electrical stimulation produced hemispasm of the larynx. Results were consistent with studies in the literature of recurrent laryngeal nerve stimulation in animal and human models. The vagus nerve provides relatively easy access for implantation of electrodes to provide electrical stimulation to the muscles of the larynx. Vagal nerve stimulation may prove efficacious in the treatment of movement disorders of the larynx; further study is needed.

INTRACOCHLEAR ELECTRICAL STIMULATION OF THE AUDITORY NERVE IN DEAF KITTENS

The effects of long-term electrical stimulation of the auditory nerve on the morphology of the cochlear nucleus were investigated in young pharmacologically deafened kittens. Comparing the amplitude of EABR with the soma area, there was a strong positive correlation between the amplitude of EABR and the soma area of neurons within the anterior ventral cochlear nucleus on the stimulated side. However, there was no correlation between the amplitude of EABR and the soma area of neurons within the unstimulated anterior ventral cochlear nucleus. In addition, there was no correlation between the amplitude of EABR and the survival rate of spiral ganglion cells. This showed that EABR may be affected not only by the survival rate of the spiral ganglion cell, but also by the development of the central auditory nervous system in kittens, which were deafened under the development of the central auditory nervous system.

Effect of long-term electrical stimulation of rabbit fast muscles on the reactivity of their supplying arteries.

Rabbit fast hindlimb muscle (tibialis anterior, extensor digitorum longus and peroneal muscles) were stimulated for 14 days, 8 h/day using implanted electrodes, with two different frequencies of stimulation (continuous at 10 Hz or 3 bursts/min at 40 Hz) giving the same total number of stimuli. Both patterns of stimulation resulted in a different pattern of flow and perfusion pressure, with lowered perfusion pressure during contractions in muscles stimulated at 10 Hz and intermittent increase during the peak of tetanic contractions in muscle stimulated at 40 Hz. The arteries supplying the stimulated muscle (anterior tibial artery) were then tested for reactivity to noradrenaline in vitro. Maximal tension developed by control arteries (supplying the contralateral nonstimulated muscles) was 18 +/- 1.4 g/mg dry weight in response to 10(-5) M noradrenaline. Arteries supplying muscle stimulated at 10 Hz showed a significant increase of the maximal response (22 +/- 1.5 g/mg) with the same dose. Arteries supplying muscles that had been stimulated at 40 Hz showed decreased response with maximal tension 9.1 +/- 1.2 g/mg. Noradrenaline uptake and clearance showed similar values in control vessels and those stimulated at either frequency. Thus, long-term stimulation of skeletal muscles can modify the reactivity of supplying arteries; the response varied with the pattern of contractions and may be explained by a different pattern of flow changes.

Electrical stimulation of the auditory nerve in deaf kittens: Effects on cochlear nucleus morphology

The present study examines the effects of long-term electrical stimulation of the auditory nerve on the morphology of neurons in the cochlear nucleus in young, sensorineural deaf animals. Kittens, systemically deafened using kanamycin and ethacrynic acid, received bilateral cochlear implants and were stimulated unilaterally for periods of up to four months. After sacrifice, cross-sectional areas of neuron somata were measured with an image-analysis system and compared using nonparametric statistics. The areas of cell somata within the anteroventral cochlear nucleus (AVCN) on the stimulated side were significantly larger than those of corresponding somata on the control, unstimulated side ( P $ ̌ 0.001 ). However, there was no statistically significant difference among dorsal cochlear nucleus (DCN) neurons. These results indicate that long-term electrical stimulation of the auditory nerve can at least partially negate some effects of early postnatal auditory deprivation at the level of the cochlear nucleus.

Effects of long-term electrical stimulation on sarcoplasmic reticulum of fast rabbit muscle

Long-term stimulation of the nerve innervating a fast muscle with the frequency pattern resembling that of a motoneuron to a slow muscle has been shown to produce marked changes in the activity pattern of enzymes of energy-supplying metabolism, the isozyme pattern of lactate dehydrogenase and some histochemical characteristics [ 1-3 ] . These changes reflect a transformation of the fast into a slower muscle. This transformation is emphasized by corresponding changes in the contractile parameters, e.g. enlargement in contraction time [4]. Recent studies [S] have indicated concomitant changes in the pattern of myosin light chains and the specific activities of Ca*‘-activated and K’-EDTA-activated ATPase of myosin. However, these latter changes appeared only after a stimulation period

Effects of long-term electrical stimulation on some contractile and metabolic characteristics of fast rabbit muscles.

Intermittant long-term stimulation of fast rabbit muscles up to 28 days with a frequency pattern resembling that of a slow muscle (10 Imp/sec) led to a slowing of the time course of contraction already during the first week. There was an increase of tetanic tension as well. The observed rearrangement of activities of key enzymes of energy supplying metabolism was found to occur sequentially. Decreases of extramitochondrial enzymes of glycogenolysis (phosphorylase), glycolysis (triosephosphate dehydrogenase, lactate dehydrogenase) and energy rich phosphate transfer were found initially together with a decrease of mitochondrial glycerolphosphate dehydrogenase. The isozyme pattern of lactate dehydrogenase was changed. Large initial increases were found in enzymes involved in glucose phosphorylation (hexokinase) and fatty acid activation (palmitoyl-CoA synthetase). Later an increase of key enzymes of the citric acid cycle (citrate synthase) and fatty acid oxidation (3-hydroxyacyl-CoA dehydrogenase) as well as ketone body utilization (3-ketoacid-CoA transferase) could be shown. Histochemical staining and comparative activity determination of succinate dehydrogenase in single fibres revealed that the mosaic like fibre composition of the fast muscle was transformed into a more uniform population resembling that of a predominantly slow muscle.

Tubocurarine binding in undercut cerebral cortex and the effect of long-term electrical stimulation

(1) An in vitro technique was used to study the binding capacity of the acetylcholinesterase (AChE)-rich synaptic membrane fraction of cat cerebral cortex for dimethyl-[ 14C]- d-tubocurarine. Observations were made on the effect of undercutting and long-term electrical stimulation of the undercut cortex upon this binding. (2) Undercutting increased the binding of dimethyl-[ 14C]- d-tubocurarine by 63% as compared with the contralateral control cortex. In parallel studies long-term electrical stimulation of undercut cortex appreciably reduced this expected increase. (3) The binding of dimethyl-[ 14C]- d-tubocurarine to the membranes was more directly related to membrane protein levels than to the AChE activity associated with them. (4) Supersensitivity of undercut cerebral cortex is likely the result of deafferentation resulting in synaptic disuse and in a concomitantly increasing sensitivity of a post-synaptic receptor or receptors.