Effects Of Chronic Electrical Stimulation Research Articles

Chronic electrical stimulation induces functional network changes in cortical neuron cultures

Recent studies demonstrated that a functional brain network could be regarded as a complex network. With the help of network theory, neuroscientists can identify common organizational principles of the functional brain networks. As a consequence, some non-random organizational features, such as “small world” (most of the nodes are not connected directly but can communicate with few intermediate relay steps) and “rich club” (nodes that are rich in connections tend to form strongly interconnected clubs), have been found in functional brain network. Recently, the “small world” organizational feature of neuronal functional networks in vitro was found to be influenced by external applications. However, little is known about the influence of chronic electrical stimulation on functional networks of dissociated cortical cultures during network development. In the present study, cortical cultures were electrically stimulated at a frequency of 0, 0.02, and 0.2 Hz, between 7 and 26 days in vitro (DIV). The spontaneous activity of the cortical cultures was recorded using MEAs. Next, a cross-covariance method and graph theory were applied to investigate organizational feature of functional networks. Our results showed that over 3 weeks of stimulation, the network density significantly increased with maturation in the control and 0.02 Hz stimulation groups, but not in 0.2 Hz stimulation groups. Moreover, all the cultures had a small-world topology at 14, 18, 22, and 26 DIV, free from the effect of chronic electrical stimulation. Besides, we found an asymmetry effect that partial electrical stimulation inhibited the formation of node connections in stimulated areas. This effect was more pronounced at 0.2 Hz than at 0.02 Hz stimulation. Our results suggest that electrical stimulation does not affect the small-world properties of neural cultures. Instead, electrical stimulation modulates connectivity patterns, and neurons within the stimulated area are less connected than neurons outside the stimulated area.

Chronic Electrical Stimulation of the Otolith Organ: Preliminary Results in Humans with Bilateral Vestibulopathy and Sensorineural Hearing Loss

Introduction: Bilateral vestibulopathy is an important cause of imbalance that is misdiagnosed. The clinical management of patients with bilateral vestibular loss remains difficult as there is no clear evidence for an effective treatment. In this paper, we try to analyze the effect of chronic electrical stimulation and adaptation to electrical stimulation of the vestibular system in humans when stimulating the otolith organ with a constant pulse train to mitigate imbalance due to bilateral vestibular dysfunction (BVD). Methods: We included 2 patients in our study with BVD according to Criteria Consensus of the Classification Committee of the Bárány Society. Both cases were implanted by using a full-band straight electrode to stimulate the otoliths organs and simultaneously for the cochlear stimulation we use a perimodiolar electrode. Results: In both cases Vestibular and clinical test (video head impulse test, videonistagmography cervical vestibular evoked myogenic potentials, cVEMP and oVEMP), subjective visual vertical test, computerized dynamic posturography, dynamic gait index, Time UP and Go test and dizziness handicap index) were performed. Posture and gait metrics reveal important improvement if compare with preoperartive situation. Oscillopsia, unsteadiness, independence and quality of life improved to almost normal situation. Discussion/Conclusion: Prosthetic implantation of the otolith organ in humans is technically feasible. Electrical stimulation might have potential effects on balance and this is stable after 1 year follow-up. This research provides new possibilities for the development of vestibular implants to improve gravito-inertial acceleration sensation, in this case by the otoliths stimulation.

The Effects of Chronic Electrical Stimulation Evaluation Functional and Electrical Properties of Muscle in a Small Group of Patients with Congenital Muscle Disorders

BackgroundIn the case of Congenital Muscle Disorders like Myotonic Dystrophy type 1 (DM1) the rehabilitative interventions have always been aimed at muscle strengthening, increasing of fatigue resistance and improving of aerobic metabolism efficiency whereas the electrical membrane fault has always been addressed pharmacologically. Neuromuscular electrical stimulation (NMES) is a useful therapeutic tool in sport medicine and in the rehabilitation of many clinical conditions characterized by motor impairment such as stroke, cerebral palsy and spinal cord injury.The aim of our pilot study was to evaluate the effects of chronic electrical stimulation both on functional and electrical properties of muscle in a small group of patients with condenital muscle disorders.Materials and methodsfive DM1 patients and one patient with Congenital Myotonia (CM) performed a home electrical stimulation of the tibialis anterior muscle lasting 15 days with a frequency of two daily sessions of 60 minutes each. Muscle strength was assessed according to the MRC scale (Medical Research Council) and functional tests (10 Meter Walking Test, 6 Minutes Walking Test – MWT and Timed Up and Go Test – TUG test) were performed. We analyzed the average rectified value of sEMG signal amplitude (ARV) to characterize the sarcolemmal excitability.ResultsAfter the treatment an increase of muscle strength in those DM1 patients with a mild strength deficit was observed. In all subjects an improvement of 10 MWT was recorded. Five patients improved their performance in the 6 MWT. In TUG test 4 out of 6 patients showed a slight reduction in execution time. All patients reported a subjective improvement when walking. A complete recovery of the normal increasing ARV curve was observed in 4 out of 5 DM1 patients; the CM patient didn't show modification of the ARV pattern.ConclusionsNMES determined a clear‐cut improvement of both the muscular weakness and the sarcolemmal excitability alteration in our small group of DM1 patients. Therefore this rehabilitative approach, if confirmed by further extensive studies, could be considered early in the management of muscular impairment in these patients. An attractive hypothesis to explain our encouraging result could be represented by a functional inhibition of small conductance calcium‐activated potassium channels expressed 3 (SK3) in muscle of DM1 subjects.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

F05. Neurophysiological effects of chronic subthreshold cortical stimulation for focal epilepsy: Spike and spontaneous ECoG activity

Neurostimulation is a treatment option for drug-resistant focal epilepsy. Chronic subthreshold cortical stimulation (CSCS) is a novel, promising technique that directly targets the seizure onset zone (SOZ) with continuous electrical stimulation. Prior retrospective analyses have shown reduced seizure frequencies and improved quality of life. Here, we investigate underlying neurophysiological changes induced by CSCS in order to gain an insight into the mechanism underlying the clinical effect of chronic electrical stimulation in focal epilepsy. We examined intracranial EEG data from seven patients with drug-resistant focal epilepsy and SOZs located in eloquent cortex who underwent continuous stimulation during their hospitalization. Subdural grid electrodes were implanted, and after the SOZ was localized to eloquent cortex, 2 Hz electrical stimulation was applied to contacts targeting the SOZ. Ninety minutes of intracranial EEG from a 4 × 4 electrode grid was analyzed before and during stimulation. Electrophysiological parameters were estimated for both pre-stimulation and stimulation data. Power spectrum and coherence of background activity was analysed together with spiking activity characteristics including spike rate, spike amplitude, and spike duration. Cortical stimulation resulted in a marked reduction of the amplitudes of background activity across all channel types for frequencies 5–40 Hz, particularly over SOZ electrodes. During cortical stimulation there was increased coherence between all electrodes and a decrease in spike rate, greatest over SOZ (p < 0.001). Spike-rate coherence was greatest within and between SOZ for pre-stimulation recordings and showed a significant decrease with cortical stimulation for electrodes near SOZ (p < 0.001). No such effect was seen for the other electrodes. Analysis of spike amplitudes showed that cortical stimulation resulted in a clear reduction of spikes over SOZ electrodes (p < 0.001) and only minor reductions for other electrodes (p < 0.001). Moreover, stimulation onset resulted in minor changes in the distribution of spike durations over all electrodes (p < 0.001). Spike-rate and power of background activity showed a significant correlation (p < 0.01). These results show changes in cortical electrophysiology during CSCS over the SOZ where reduction in interictal spikes is correlated with an attenuation of background activity. This suggests a possible causal relationship between background activity and interictal spikes and with seizure frequency rate. With an improved understanding of chronic electrical stimulation better stimulation paradigms might be developed for improved suppression of seizure frequency.

Local inner ear application of dexamethasone in cochlear implant models is safe for auditory neurons and increases the neuroprotective effect of chronic electrical stimulation.

Dexamethasone (DEX) can reduce fibrous tissue growth as well as loss of residual hearing which may occur after cochlear implantation. Little is known about the effect of local inner ear DEX treatment on the spiral ganglion neurons (SGN), which are the target of the electrical stimulation with a cochlear implant (CI). Three different clinically relevant strategies of DEX-delivery into the inner ear were used. DEX was either eluted from the electrode carriers’ silicone, released from a reservoir by passive diffusion, or actively applied using a pump based system. The effect of the locally applied DEX on SGN density, size and function was evaluated. DEX did not affect the SGN density compared to the relevant control groups. Simultaneously applied with chronic electrical stimulation (ES), DEX increased the neuroprotective effect of ES in the basal region and the hearing threshold tended to decrease. The EABR thresholds did not correlate with the relevant SGN density. When correlating the SGN number with fibrosis, no dependency was observed. DEX concentrations as applied in these animal models are safe for inner ear delivery in terms of their effect on SGN density. Additionally, DEX tends to improve the neuroprotective effect of chronic electrical stimulation by increasing the number of surviving neurons. This is an important finding in regard to clinical applications of DEX for local treatment of the inner ear in view of cochlear implantation and other applications.

Deep Brain Stimulation for Alzheimer's Disease.

High-frequency deep brain stimulation (DBS) was introduced in the late 1980s for the treatment of movement disorders. This reversible, adjustable, and non-ablative therapy has been used to treat more than 100,000 people worldwide. The surgical procedure used to implant the DBS system, as well as the effects of chronic electrical stimulation, have been shown to be safe and effective through many clinical trials. Given the ability to therapeutically modulate the motor circuits of the brain in this manner, clinicians have considered using DBS for other neurodegenerative and neuropsychiatric disorders involving non-motor circuits, including appetite, mood, and cognition. This article highlights several recent studies exploring the feasibility of using DBS to modulate memory, specifically in the context of memory disorders such as Alzheimer disease.

Chronic pudendal neuromodulation using an implantable microstimulator improves voiding function in diabetic rats

AbtractObjective. Few studies have investigated the feasibility of using chronic pudendal neuromodulation for improving voiding function in patients with diabetes who are also experiencing urinary retention. The present study investigated the effects of chronic electrical stimulation (ES) of the sensory branch of the pudendal nerve on voiding function in diabetic rats. Approach. A custom-made implantable microstimulation system was designed and manufactured for chronic implantation in normal control (NC) and diabetic rats. After three or six weeks of pudendal neuromodulation, the intravesical pressure, external urethral sphincter electromyograms (EUS-EMGs), and urine flow rate (UFR) of all rats were simultaneously recorded to assess the effects of chronic pudendal ES on voiding function. Morphological changes in pudendal axons were assessed through hematoxylin and eosin (H&E) staining. Results. Abnormal cystometric measurements, including an increased volume threshold, contraction amplitude, and residual volume (RV) as well as a decreased burst period (BP) indicated voiding dysfunction in the diabetic rats with sham ES for three or six weeks. However, real ES for three or six weeks reversed these abnormal results; these parameters became similar to those of the NC rats and, consequently, voiding efficiency (VE) increased significantly from 17%–45% to 51%–57%. The cross-sectional area and axonal density of the pudendal nerve decreased in all the diabetic rats with sham ES for six weeks; however, these values increased significantly after real ES for six weeks. Significance. This study demonstrated the feasibility of using chronic pudendal neuromodulation for improving voiding function in diabetic rats. These results may facilitate the development of an advanced neural prosthesis for restoring bladder function in clinical settings.

Chronic muscle stimulation improves muscle function and reverts the abnormal surface EMG pattern in Myotonic Dystrophy: a pilot study

BackgroundTo date, in Myotonic Dystrophy type 1 (DM1) the rehabilitative interventions have always been aimed at muscle strengthening, increasing of fatigue resistance and improving of aerobic metabolism efficiency whereas the electrical membrane fault has always been addressed pharmacologically. Neuromuscular electrical stimulation (NMES) is a useful therapeutic tool in sport medicine and in the rehabilitation of many clinical conditions characterized by motor impairment such as stroke, cerebral palsy and spinal cord injury.The aim of our pilot study was to evaluate the effects of chronic electrical stimulation both on functional and electrical properties of muscle in a small group of DM1 patients.MethodsFive DM1 patients and one patient with Congenital Myotonia (CM) performed a home electrical stimulation of the tibialis anterior muscle lasting 15 days with a frequency of two daily sessions of 60 minutes each. Muscle strength was assessed according to the MRC scale (Medical Research Council) and functional tests (10 Meter Walking Test, 6 Minutes Walking Test and Timed Up and Go Test) were performed. We analyzed the average rectified value of sEMG signal amplitude (ARV) to characterize the sarcolemmal excitability.ResultsAfter the treatment an increase of muscle strength in those DM1 patients with a mild strength deficit was observed. In all subjects an improvement of 10MWT was recorded. Five patients improved their performance in the 6MWT. In TUG test 4 out of 6 patients showed a slight reduction in execution time. All patients reported a subjective improvement when walking. A complete recovery of the normal increasing ARV curve was observed in 4 out of 5 DM1 patients; the CM patient didn’t show modification of the ARV pattern.ConclusionsNMES determined a clear-cut improvement of both the muscular weakness and the sarcolemmal excitability alteration in our small group of DM1 patients. Therefore this rehabilitative approach, if confirmed by further extensive studies, could be considered early in the management of muscular impairment in these patients. An attractive hypothesis to explain our encouraging result could be represented by a functional inhibition of SK3 channels expressed in muscle of DM1 subjects.

Cochlear implants in children with vestibular hypofunction

ObjectiveThe aim of this work was to evaluate the long term effect of cochlear implants electrical stimulation on the function of a hypo-excitable lateral semicircular canal and saccule. MethodsA total number of 45 children (21 males and 24 females) between 5 and 6years of age were included in this study. All patients were diagnosed with severe or profound sensorineural hearing loss and bilateral or unilateral hypofunction of the peripheral vestibular system. All of the subjects received multichannel cochlear implants. An initial vestibular system assessment was done prior to implantation by bithermal caloric irrigation and vestibular myogenic evoked potential (VEMP). Vestibular evaluation was done 1, 12 and 24months after switching on the device. ResultsNineteen subjects (42%) showed improvement of the lateral canal response and 10 of them showed identifiable VEMP response at 90 and 100dBnHL. ConclusionWhile the results of the current study showed positive impact of the CI on the hypoexcitable vestibular system. The late effects of chronic electrical stimulation on the vestibular system need to be further assessed.

Synchrotron light source imaging of brain tissue shows changes in iron concentration after chronic implantation of electrodes and electrical stimulation

PURPOSEVarious metallic electrodes are used in research and clinical applications because of their purported biological compatibility. However, little is known about the effects on surrounding tissue following subsequent stimulation. Using X‐ray fluorescence imaging, we examined metal distribution in the brain after stimulation with three types of electrodes.METHODSBilateral implantation of stainless steel, nickel‐chromium, or platinum‐iridium electrodes into amygdala was used in a rat preparation of epilepsy. Stage 5 seizures were kindled by a once‐daily application of electrical stimulation. Rapid scanning X‐Ray fluorescence and microprobe analysis of brain sections were performed using the imaging beam lines at the Stanford Synchrotron Radiation Lightsource.RESULTSImages showed elevated iron concentrations around the electrode tips in both control and kindled tissue. Concentrations varied according to electrode type and were greater in kindled tissue as compared to yoked controls.CONCLUSIONSChronic implantation of electrodes in the brain results in an increased concentration of iron around the electrode track, which is further increased by stimulation. These findings raise the issue of possible adverse effects from these metal depositions and suggest the need to evaluate the effects of chronic electrical stimulation in clinical settings.Support: NSERC, CIHR

Stimulation by cochlear implant in unilaterally deaf rats reverses the decrease of inhibitory transmission in the inferior colliculus

In the last decade, numerous studies have investigated synaptic transmission changes in various auditory nuclei after unilateral cochlear injury. However, few data are available concerning the potential effect of electrical stimulation of the deafferented auditory nerve on the inhibitory neurotransmission in these nuclei. We report here for the first time the effect of chronic electrical stimulation of the deafferented auditory nerve on alpha1 subunit of the glycinergic receptor (GlyRalpha1) and glutamic acid decarboxylase (GAD)67 expression in the central nucleus of inferior colliculus (CIC). Adult rats were unilaterally cochleectomized by intracochlear neomycin sulphate injection. Fifteen days later, the ipsilateral auditory nerve was chronically stimulated either 4, 8 or 22 h daily, for 5 days using intracochlear bipolar electrodes. GlyRalpha1 and GAD67 mRNA and protein were quantified in the CIC using in situ hybridization and immunohistofluorescence methods. Our data showed that as after surgical ablation, GlyRalpha1 and GAD67 expression were strongly decreased in the contralateral CIC after unilateral chemical cochleectomy. Most importantly, these postlesional down-modulations were significantly reversed by chronic electrical stimulation of the deafferented auditory nerve. This recovery, however, did not persist for more than 5 days after the cessation of the deafferented auditory nerve electrical stimulation. Thus, downregulations of GlyRalpha1 and GAD67 may be involved both in the increased excitability observed in the CIC after unilateral deafness and consequently in the tinnitus frequently observed in unilateral adult deaf patients. Electrical stimulation of the deafferented auditory nerve in patients may be a potential new approach for treating tinnitus with unilateral hearing loss.

Effects of chronic electrical stimulation on paralyzed expiratory muscles

Following spinal cord injury, the expiratory muscles develop significant disuse atrophy characterized by reductions in their weight, fiber cross-sectional area, and force-generating capacity. We determined the extent to which these physiological alterations can be prevented with electrical stimulation. Because a critical function of the expiratory muscles is cough generation, an important goal was the maintenance of maximal force production. In a cat model of spinal cord injury, short periods of high-frequency lower thoracic electrical spinal cord stimulation (SCS) at the T(10) level (50 Hz, 15 min, twice/day, 5 days/wk) were initiated 2 wk following spinalization and continued for a 6-mo period. Airway pressure (P)-generating capacity was determined by SCS. Five acute, spinalized animals served as controls. Compared with controls, initial P fell from 43.9 +/- 1.0 to 41.8 +/- 0.7 cmH(2)O (not significant) in the chronic animals. There were small reductions in the weight of the external oblique, internal oblique, transverses abdominis, internal intercostal, and rectus abdominis muscles (not significant for each). There were no significant changes in the population of fast muscle fibers. Because prior studies (Kowalski KE, Romaniuk JR, DiMarco AF. J Appl Physiol 102: 1422-1428, 2007) have demonstrated significant atrophy following spinalization in this model, these results indicate that expiratory muscle atrophy can be prevented by the application of short periods of daily high-frequency stimulation. Because the frequency of stimulation is similar to the expected pattern of clinical use for cough generation, the daily application of electrical stimulation could potentially serve the dual purpose of maintenance of expiratory muscle function and airway clearance.

Effects of chronic electrical stimulation on long-term denervated muscles of the rabbit hind limb

We investigated the extent to which activity induced by chronic electrical stimulation could restore the mass and contractile function of rabbit tibialis anterior (TA) muscles that had undergone atrophy as a result of prolonged denervation. Denervation was carried out by selectively interrupting the motor nerve branches to the ankle dorsiflexors in one hind limb. Stimulators were implanted, with electrodes on the superficial and deep surfaces of the denervated TA muscle. Ten weeks later, the mass and mid-belly cross-sectional area (CSA) of TA muscles subjected to denervation alone had fallen to approximately 40% of normal. At this stage, stimulators in the other rabbits were activated for 1 h/day to deliver 20-ms rectangular bipolar constant-current pulses of 4 mA amplitude at 20 Hz with a duty cycle of 1s ON/2s OFF, a total of 24,000 impulses/day. The animals were examined after a further 2, 6 or 10 weeks. Stimulation restored the wet weight of the denervated muscles to values not significantly different to those of normal, innervated controls. It increased CSA from 39% to 66% of normal, and there was a commensurate increase in maximum isometric tetanic force from 27% to 50% of normal. Light and electron microscopic examination revealed a marked improvement in the size, packing, and internal organization of the stimulated-denervated muscle fibres, suggestive of an ongoing process of restoration. Excitability, contractile speed, power, and fatigue resistance had not, however, been restored to normal levels after 10 weeks of stimulation. Similar results were found for muscles that had been denervated for 39 weeks and then stimulated for 12 weeks. The study demonstrates worthwhile benefits of long-term electrical stimulation in the treatment of established denervation atrophy.

IS A COMPUTATIONAL MODEL USEFUL TO UNDERSTAND THE EFFECT OF DEEP BRAIN STIMULATION IN PARKINSON'S DISEASE?

A growing number of computational models have been proposed over the last few years to help explain the therapeutic effect of deep brain stimulation (DBS) on motor disorders in Parkinson's disease (PD). However, none of these has been able to explain in a convincing manner the physiological mechanisms underlying DBS. Can these models really contribute to improving our understanding? The model by Rubin and Terman [31] represents one of the most comprehensive and biologically plausible models of DBS published recently. We examined the validity of the model, replicated its simulations and tested its robustness. While our simulations partially reproduced the results presented by Rubin and Terman [31], several issues were raised including the high complexity of the model in its non simplified form, the lack of robustness of the model with respect to small perturbations, the nonrealistic representation of the thalamus and the absence of time delays. Computational models are indeed necessary, but they may not be sufficient in their current forms to explain the effect of chronic electrical stimulation on the activity of the basal ganglia (BG) network in PD.

Chronic electrical stimulation of four acupuncture points on rat diabetic neuropathy.

The main purpose of this study is to investigate the effects of chronic electrical stimulation of acupuncture points on rat diabetic neuropathy. Diabetes mellitus was induced by a single dose of intravenous streptozotocin. The efficacies of several different protocols of electrical stimulation were compared. The evaluation measures included nerve conduction velocity, tactile threshold and blood perfusion on eye and footpad. Electrical stimulation was administered 30 min/day for 4 weeks. On the 4th weekend of stimulation, when compared with the control group, the stimulated groups showed differential benefits on different evaluation measures. The results indicated that chronic electrical stimulation could reduce the functional deficits of diabetic neuropathy.

Vagal nerve stimulation markedly improves long-term survival after chronic heart failure in rats.

Diminished cardiac vagal activity and higher heart rate predict a high mortality rate of chronic heart failure (CHF) after myocardial infarction. We investigated the effects of chronic electrical stimulation of the vagus nerve on cardiac remodeling and long-term survival in an animal model of CHF after large myocardial infarction. Two weeks after the ligation of the left coronary artery, surviving rats were randomized to vagal- and sham-stimulated groups. Using an implantable miniature radio-controlled electrical stimulator, we stimulated the right vagal nerve of CHF rats for 6 weeks. The intensity of electrical stimulation was adjusted for each rat, so that the heart rate was lowered by 20 to 30 beats per minute. The treated rats had significantly lower left ventricular end-diastolic pressure (17.1+/-5.9 versus 23.5+/-4.2 mm Hg, P<0.05) and higher maximum dp/dt of left ventricular pressure (4152+/-237 versus 2987+/-192 mm Hg/s, P<0.05) than the untreated rats. Improvement of cardiac pumping function was accompanied by a decrease in normalized biventricular weight (2.75+/-0.25 versus 3.14+/-0.22 g/kg, P<0.01). Although the 140-day survival of the untreated group was only half, vagal stimulation markedly improved the survival rate (86% versus 50%, P=0.008). Vagal stimulation therapy achieved a 73% reduction in a relative risk ratio of death. Vagal nerve stimulation markedly improved the long-term survival of CHF rats through the prevention of pumping failure and cardiac remodeling.

The Lateral Hypothalamic Area: Peculiarities of Aging and the Effect of Chronic Electrical Stimulation on the Lifespan in Rats

Age-related morphological and functional changes in the lateral hypothalamic area (LHA) were studied in experiments on young adult (6-8 months) and old (26-28 months) male Wistar rats. It was found that during aging the neuronal density in the LHA decreased, and significant qualitative destructive and dystrophic changes in the neuronal population developed. The background impulse activity of LHA neuronal units, the mass background electrical activity recorded from this structure, and the Na+, K+-ATPase activity decreased during aging. In old rats, the rate of LHA self-stimulation was lower, and the range of reinforcing current amplitudes, which provided self-stimulation intensity close to the maximum, was narrower than in adult animals. Chronic electrical LHA stimulation in old rats ensured an increase in the lifespan and maximum life expectancy in these animals. In addition, the lifespan positively correlated with the duration of LHA stimulation. It is concluded that lowering of the functional activity of the LHA neural systems is one of the substantial aspects of the aging process, and activation of this structure in old animals by its chronic electrical stimulation can exert a geroprotective effect.

Changes in FGF and FGF receptor expression in low-frequency-stimulated rat muscles and rat satellite cell cultures

This study compares effects of chronic electrical stimulation on the expression levels of FGF-1, FGF-2 and their receptors (FGFR1, FGFR4) in rat tibialis anterior (TA) muscle of hypothyroid rat, as well as in satellite cell cultures derived from normal rat TA and soleus (SOL) muscles. In 5-day (5-d)-stimulated hypothyroid TA muscle, FGF-1 and FGF-2 mRNA levels were threefold elevated over control. FGFR1 and FGFR4 mRNAs were twofold and 1.5-fold elevated, respectively. In longer stimulated muscles, FGF-1 and FGFR4 mRNAs returned to basal levels, whereas FGF-2 mRNA remained elevated. FGFR1 mRNA decreased to control levels in 10-d stimulated muscles, but increased again after 20 days of stimulation. SOL- and TA-derived satellite cell cultures were stimulated for 5 days. At this time point, changes in myosin heavy chain isoforms were detectable consisting of increases in MHCI mRNA and decreases in MHCIIb and MHCIId mRNA. The comparison between 5-d-stimulated hypothyroid TA muscle and 5-d-stimulated TA- and SOL-derived satellite cell cultures revealed differences in the expression of FGF-1 and FGF-2, but similar expression levels of FGFR1 and FGFR4. Even though FGF-1 and FGF-2 mRNAs were elevated in the satellite cell cultures, their increases were less pronounced than in the stimulated hypothyroid muscle. Taking into consideration that skeletal muscle contains muscle fibres and various non-muscle tissues, e.g. blood vessels, these results suggest that the latter contribute to the observed increases in FGF-1 and FGF-2 expression in stimulated muscle.

Effect of chronic electrical stimulation and beta-GPA diet on GLUT4 protein concentration in rat skeletal muscle.

The present study investigated whether alterations in the muscle high energy phosphate state initiates the contraction-induced increase in skeletal muscle GLUT4 protein concentration. Sprague-Dawley rats were provided either a normal or a 2% beta-guanidinoproprionic acid (beta-GPA) diet for 8 weeks and then the gastrocnemius of one hind limb was subjected to 0, 14 or 28 days of chronic (24 h day-1) low-frequency electrical stimulation (10 Hz). The beta-GPA diet, in the absence of electrical stimulation, significantly reduced ATP, creatine phosphate, creatine and inorganic phosphate and elevated GLUT4 protein concentration by 60% without altering adenylate cyclase activity or cAMP concentration. Following 14 days of electrical stimulation, GLUT4 protein concentration was elevated above non-stimulated muscle in both groups but was significantly more elevated in the beta-GPA group. Concurrent with this greater rise in GLUT4 protein concentration was a greater decline in the high energy phosphates and a greater rise in cAMP. After 28 days of electrical stimulation, GLUT4 protein concentration and cAMP stabilized and was not different between diet treatments. However, the high energy phosphates were significantly higher in the normal diet rats as opposed to the beta-GPA rats. These findings therefore suggest that a reduction in cellular energy supply initiates the contraction-induced increase in muscle GLUT4 protein concentration, but that a rise in cAMP may potentiate this effect.

Effects of chronic electrical stimulation on cochlear nuclear neuron size in deaf kittens

It is now well recognized that normal afferent innervation is necessary for development of the auditory pathway. This study investigated the effect of chronic electrical stimulation of the auditory nerve on the size of cochlear nucleus somata of neonatally deafened kittens. Four kittens were deafened by using kanamycin and ethacrynic acid at 10 days of age and implanted at various ages with an active intracochlear implant in the left side and a dummy implant in the right side, and chronically electrically stimulated from ages 98-142 days for approximately 1000 hours at twice the EABR threshold. After chronic stimulation or after an equivalent period in the controls, the animals were injected with 2-deoxyglucose (2DG) and stimulated electrically for 45 minutes, then processed for autoradiography. Then the sections were stained for Nissle substance, and the cross-sectional areas (CSSA) of approximately 33,000 neuron somata in the cochlear nuclei were measured with an image-analysis system. Soma sizes in regions with 2DG uptake were compared with those without the uptake. The CSSA of 2DG-labeled regions was usually significantly larger than that of the unlabeled regions, but there were no significant right-left differences. Thus, chronic electrical stimulation of a restricted sector of the cochlea is correlated with a larger soma size in the corresponding region of the cochlear nucleus.