Hours Of Electrical Stimulation Research Articles

Electrofluidic control of bioactive molecule delivery into soft tissue models based on gelatin methacryloyl hydrogels using threads and surgical sutures

The delivery of bioactive molecules (drugs) with control over spatial distribution remains a challenge. Herein, we demonstrate for the first time an electrofluidic approach to controlled delivery into soft tissue models based on gelatin methacryloyl (GelMA) hydrogels. This was achieved using a surgical suture, whereby transport of bioactive molecules, including drugs and proteins, was controlled by imposition of an electric field. Commonly employed surgical sutures or acrylic threads were integrated through the hydrogels to facilitate the directed introduction of bioactive species. The platform consisted of two reservoirs into which the ends of the thread were immersed. The anode and cathode were placed separately into each reservoir. The thread was taken from one reservoir to the other through the gel. When current was applied, biomolecules loaded onto the thread were directed into the gel. Under the same conditions, the rate of movement of the biomolecules along GelMA was dependent on the magnitude of the current. Using 5% GelMA and a current of 100 µA, 2 uL of fluorescein travelled through the hydrogel at a constant velocity of 7.17 ± 0.50 um/s and took less than 8 minutes to exit on the thread. Small molecules such as riboflavin migrated faster (5.99 ± 0.40 μm/s) than larger molecules such as dextran (2.26 ± 0.55 μm/s with 4 kDa) or BSA (0.33 ± 0.07 μm/s with 66.5 kDa). A number of commercial surgical sutures were tested and found to accommodate the controlled movement of biomolecules. Polyester, polyglactin 910, glycolide/lactide copolymer and polyglycolic acid braided sutures created adequate fluid connection between the electrodes and the hydrogel. With a view to application in skin inflammatory diseases and wound treatment, wound healing, slow and controlled delivery of dexamethasone 21-phosphate disodium salt (DSP), an anti-inflammatory prodrug, was achieved using medical surgicryl PGA absorbable suture. After 2 hours of electrical stimulation, still 81.1% of the drug loaded was encapsulated within the hydrogel.

MP30-01 IDENTIFYING A SENSITIVE AND SPECIFIC PANEL OF DNA METHYLATION MARKERS IN MODELS OF CYSTITIS

stimulation of the pudendal nerve upregulates neurotrophin expression and improves recovery in a rat model of SUI. METHODS: Rats received 1 hour of electrical stimulation (20 Hz, 0.3 mA, 0.1 ms pulse) or sham stimulation of the pudendal nerve immediately after simulated birth injury, consisting of vaginal distension and pudendal nerve crush. A separate cohort of rats received sham injury and no treatment. All rats underwent stimulation or sham stimulation for 1 hour twice per week for 2 weeks. Brain derived neurotrophic factor (BDNF) and bII-tubulin (neuronal cytoskeletal protein and marker of neuroregenerative response) expression in Onuf’s nucleus was measured with RT-PCR. Leak point pressure (LPP) and external urethral sphincter electromyography (EUS EMG) was performed. Data was analyzed with a two-way ANOVA and Student-Newman-Keuls posthoc pairwise comparisons with p<0.05 statistically significant. RESULTS: Compared to sham stimulation, electrical stimulation significantly increased both BDNF and bII-tubulin expression in Onuf’s nucleus, demonstrating an increased neuroregenerative response. Both LPP and baseline EUS EMG amplitude decreased significantly after injury compared to sham injury and increased significantly with stimulation compared to sham stimulation. During voiding, EUS EMG burst frequency, burst duration, and interburst interval were significantly decreased by injury compared to sham and after injury were significantly increased with electrical stimulation compared to sham. CONCLUSIONS: Pudendal nerve electrical stimulation appears to promote SUI recovery via strengthening the neuroregenerative response by upregulating BDNF expression in pudendal nerve cell bodies. Electrical stimulation may shorten postpartum SUI duration and could potentially serve as a preventative treatment for later SUI development.

Intracochlear Electrical Stimulation Suppresses Apoptotic Signaling in Rat Spiral Ganglion Neurons after Deafening in Vivo

To establish the intracellular consequences of electrical stimulation to spiral ganglion neurons after deafferentation. Here we use a rat model to determine the effect of both low and high pulse rate acute electrical stimulation on activation of the proapoptotic transcription factor Jun in deafferented spiral ganglion neurons in vivo. Experimental animal study. Hearing research laboratories of the University of Iowa Departments of Biology and Otolaryngology. A single electrode was implanted through the round window of kanamycin-deafened rats at either postnatal day 32 (P32, n = 24) or P60 (n = 22) for 4 hours of stimulation (monopolar, biphasic pulses, amplitude twice electrically evoked auditory brainstem response [eABR] threshold) at either 100 or 5000 Hz. Jun phosphorylation was assayed by immunofluorescence to quantitatively assess the effect of electrical stimulation on proapoptotic signaling. Jun phosphorylation was reliably suppressed by 100 Hz stimuli in deafened cochleae of P32 but not P60 rats. This effect was not significant in the basal cochlear turns. Stimulation frequency may be consequential: 100 Hz was significantly more effective than was 5 kHz stimulation in suppressing phospho-Jun. Suppression of Jun phosphorylation occurs in deafferented spiral ganglion neurons after only 4 hours of electrical stimulation. This finding is consistent with the hypothesis that electrical stimulation can decrease spiral ganglion neuron death after deafferentation.

Electrical Stimulation Reduces Apoptotic Signaling in SGNs

Objective: To establish the intracellular consequences of electrical stimulation (ES) to spiral ganglion neurons (SGNs) after deafferentation. SGNs die as a result of loss of hair cells, their sole afferent input. Some histologic animal studies of chronic ES after deafening show that ES alone may improve SGN survival. Here we use a rat model to determine the effect of both low and high pulse rate ES on activation of the pro-apoptotic transcription factor Jun in deafferented SGNs in vivo. Methods: A single electrode was implanted through the round window of kanamycin-deafened rats at either postnatal day 32 (P32) or P60 for 4 hours of ES (monopolar, biphasic pulses, amplitude twice eABR threshold) at either 100 or 5000 Hz. Jun phosphorylation, a proapoptotic signaling event known to occur in apoptotic SGNs after deafening, was assayed by immunofluorescence to quantitatively assess the effect of ES on proapoptotic signaling. Results: Jun phosphorylation was reliably suppressed by 100 Hz ES in deafened cochleae of P32 rats ( P = .045) but this effect was less robust when 5000 Hz ES was used. This effect was most significant in the cochlear turn just apical to the stimulating electrode and was not significant in P60 rats. Conclusion: Suppression of phospho-Jun occurs in deafferented SGNs after only 4 hours of ES, consistent with the hypothesis that ES provides trophic support to SGNs after deafferentation. Stimulation frequency may be consequential: 100 Hz ES was significantly more effective than 5000 Hz ES in suppressing phospho-Jun.

Intensive Electrical Stimulation Attenuates Femoral Bone Loss in Acute Spinal Cord Injury

To determine whether intensive electrical stimulation (ES) can reduce femoral bone mineral density (BMD) loss in acute spinal cord injury (SCI). Randomized controlled trial. Inpatient rehabilitation hospital. Twenty-six subjects with C4 to T12 American Spinal Injury Association Impairment Scale A or B SCI less than 12 weeks postinjury. The control group received usual rehabilitative care and the intervention group received usual care plus 1 hour of ES over the quadriceps 5 days per week for 6 weeks. Outcome measurements were collected at baseline, postintervention (interim), and 3 months postinjury (follow-up), and included dual energy x-ray absorptiometry, serum osteocalcin (OC), and urinary N-telopeptide (NTx). In the control group, there was increasing BMD loss with distance from the spine (lumbar -1.88%, hip -12.25%, distal femur -15.15%, proximal tibia -17.40%). This trend was attenuated over the distal femur in the ES group (lumbar -1.29%, hip -14.45%, distal femur -7.40%, proximal tibia -12.31%). NTx increased over the 3 assessments in controls ([mean ± standard deviation] 115.00 ± 34.10, 154.86 ± 70.41, and 171.33 ± 75.8 nmol/mmol creatinine) compared with the ES group (160.56 ± 140.06, 216.71 ± 128.40, and 154.67 ± 69.12 nmol/mmol creatinine)-all of which were elevated compared with the reference range, and the differences between the 2 groups were not significant. Osteocalcin levels markedly decreased in the control group (12.90 ± 7.30, 24.00 ± 4.29, and 6.40 ± 7.28 μg/L) to subnormal levels, and remained stable and in the normal range in the ES group (13.80 ± 7.64, 11.86 ± 6.77, and 14.80 ± 12.91 μg/L), although differences between the groups were not significant. Lower extremity BMD loss increases with distance from the spine. An intensive lower extremity ES program may attenuate BMD loss locally after acute motor complete SCI, although it is unknown whether these benefits are maintained in the long term.

1666 ELECTRICAL STIMULATION OF THE PUDENDAL NERVE INCREASES THE EXPRESSION OF NEUROTROPHINS IN ONUF'S NUCLEUS FOLLOWING SIMULATED CHILDBIRTH INJURY

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Female Urology II1 Apr 20101666 ELECTRICAL STIMULATION OF THE PUDENDAL NERVE INCREASES THE EXPRESSION OF NEUROTROPHINS IN ONUF'S NUCLEUS FOLLOWING SIMULATED CHILDBIRTH INJURY Hai-Hong Jiang, Bradley Gill, Levilester Salcedo, Paul Zaszczurynski, Brian Balog, Dan Li Lin, and Margot Damaser Hai-Hong JiangHai-Hong Jiang More articles by this author , Bradley GillBradley Gill More articles by this author , Levilester SalcedoLevilester Salcedo More articles by this author , Paul ZaszczurynskiPaul Zaszczurynski More articles by this author , Brian BalogBrian Balog More articles by this author , Dan Li LinDan Li Lin More articles by this author , and Margot DamaserMargot Damaser More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1490AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A combinatorial injury occurs during childbirth, involving the urethra and pudendal nerve, which can result in stress urinary incontinence (SUI). We have previously demonstrated that dual simulated childbirth injury, consisting of pudendal nerve crush (PNC) and vaginal distension (VD), results in slowed recovery of both continence function & pudendal nerve function, as well as decreased expression of brain derived neurotrophic factor (BDNF). Electrical stimulation has been shown to upregulate BDNF in motor neurons after injury. In this study, we electrically stimulated the pudendal nerve proximal to the crush site to determine if this upregulates BDNF in Onuf's nucleus as a potential treatment to facilitate nerve recovery after childbirth. METHODS Sprague-Dawley female rats were assigned to 3 groups; dual injury (n=5), sham injury (n=5), and intact control (n=5), respectively. Rats in the dual injury group received 4 hours of VD immediately followed by bilateral PNC. Rats in the sham injury group underwent sham procedures. All rats received 1 hour of electrical stimulation (20 Hz, 0.3mA, 0.1 ms duration) of the left pudendal nerve and sham stimulation of the right pudendal nerve immediately after dual or sham injury. The lumbosacral spinal cord was harvested 2 days after stimulation and was flash frozen, sectioned at L6/S1, and laser dissected to isolate Onuf's nucleus (dorsolateral motoneurons in rats). BDNF mRNA expression in Onuf's nucleus was determined by real-time RT-PCR and was normalized to expression of S-18. RESULTS Two days after dual injury, BNDF expression in Onuf's nucleus was significantly decreased in both stimulated and sham stimulated groups compared to that of intact or sham injury. BNDF expression was significantly increased on the stimulated (left) side compared to the sham stimulated (right) side 2 days after dual injury, indicating that electrical stimulation upregulates BDNF expression in Onuf's nucleus. CONCLUSIONS BDNF expression becomes deficient in Onuf's nucleus after a dual childbirth simulation injury. Electrical stimulation of the pudendal nerve proximal to the crush immediately after dual injury upregulated BDNF expression in Onuf's nucleus, suggesting that it will improve recovery after injury. Future work will be aimed at optimizing and developing electrical stimulation to facilitate recovery of the pudendal nerve after childbirth as a preventative paradigm for SUI. Cleveland, OH© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e643-e644 Peer Review Report Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hai-Hong Jiang More articles by this author Bradley Gill More articles by this author Levilester Salcedo More articles by this author Paul Zaszczurynski More articles by this author Brian Balog More articles by this author Dan Li Lin More articles by this author Margot Damaser More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Chondroitinase ABC and acute electrical stimulation are beneficial for muscle reinnervation after sciatic nerve transection in rats

Nerve regeneration and functional recovery are often incomplete after peripheral nerve damage. The aim of this study was to determine if chondroitinase ABC injection at the lesion site, 1 hour of electrical stimulation and the combination of these treatments at the time of repair could be effective in promoting muscle reinnervation. The right sciatic nerve was completely sectioned in 32 female Sprague-Dawley rats. End-to-end microsuture repair was undertaken and fibrin glue was added. Five groups were studied: 1) suture (S) + fibrin glue (F) only; 2) S + F + chondroitinase ABC; 3) S + F + electrical stimulation; 4) S + F + chondroitinase ABC + electrical stimulation; 5) uninjured nerve. Post recovery kinematics showed larger excursion of the hip-ankle-toe angle during walking in groups 2, 3 and 4 than in group 1 (p < 0.05). In vivo electromyographic activity and maximal muscle force were similar between groups 2, 3, 4 and 5, with higher values in all of them compared to group 1 (p < 0.05). Also, the distal stump of the sciatic nerve was excised, and cross-sectioning revealed that the number of axons were similar in all groups. 150 days after nerve transection, recovery was incomplete with S and F only. Chondroitinase ABC injection at the lesion site and/or 1 hour of electrical stimulation of the proximal nerve stump were beneficial in promoting nerve regeneration and functional muscle reinnervation.

The Cerebellum Modulates Rodent Cortical Motor Output after Repetitive Somatosensory Stimulation

To analyze the possible role of the cerebellum in the modulation of cortical motor output associated with repetitive electrical stimulation of the sciatic nerve in the rat. A sustained somatosensory stimulation induces an increase in the intensity of the response of the rodent motor cortex. Wistar rats were anesthetized for surgical preparation using a continuous infusion of chloral hydrate. We analyzed the response evoked by electrical stimulation of the right motor cortex before (basal condition) and after peripheral electrical stimulation of the left sciatic nerve in rats with no cerebellar intervention (n = 6), and in control rats with Ringer's infusion via a microdialysis probe (n = 8) implanted in the left cerebellar nuclei. In addition, we investigated the effects of 1) the administration of ethanol (20 mmol/L) in the left cerebellar nuclei (n = 5); 2) the administration of tetrodotoxin (10 micromol/L), a sodium channel blocker, in the left cerebellar nuclei (n = 5); 3) electrical stimulation by deep cerebellar stimulation (frequency 100 Hz) on the left side (n = 5); or 4) electrical stimulation of the cerebellar nuclei on the right side (100 Hz; n = 6). For peripheral stimulation, all of the animals received 1 hour of electrical stimulation. Trains of stimulation consisted of five stimuli (duration of 1 stimulus, 1 ms) at a rate of 10 Hz. During stimulation of the motor cortex, peak-to-peak amplitudes in responses of the left calf muscle were analyzed. Motor threshold was defined as the lowest intensity eliciting at least 5 of 10 evoked responses with an amplitude greater than 20 muV. The intensity used was 130% of the motor threshold. In the basal condition (before repetitive stimulation), amplitudes of motor responses were similar in the six groups of rats (P = 0.40). In rats without cerebellar intervention, peripheral electrical stimulation was associated with an increase of motor response to 147.4 +/- 8.5% of baseline (P < 0.001). In rats with Ringer's infusion, the motor response increased to 141.6 +/- 7.9% of baseline (P < 0.001). The administration of ethanol in the cerebellum prevented the enhancement of the response ipsilaterally. The mean +/- standard deviation (SD) of motor responses was 105.7 +/- 6.2% of baseline measurements after stimulation of the sciatic nerve (P = 0.36). The same observation was made after the infusion of tetrodotoxin (mean +/- SD of motor responses: 107.1 +/- 7.4% after peripheral stimulation [P = 0.19] and after electrical stimulation of the cerebellum on the left side [mean +/- SD of motor responses, 104.3 +/- 8.5% after peripheral stimulation, P = 0.40]). However, electrical stimulation of cerebellar nuclei on the right side did not impair the modulation of cortical motor output by sciatic nerve stimulation (mean +/- SD of motor responses, 148.4 +/- 5.8% after peripheral stimulation, P < 0.001). Until now, the increase of motor output after peripheral nerve stimulation has been considered as a plasticity directly and solely dependent on cortical structures. We demonstrate that the cerebellum plays a key role in this form of neural plasticity.

Expression of c- fos protein in rat brain after electrical stimulation of the aortic depressor nerve

To reveal central nervous system (CNS) structures involved in the baroreceptor reflex we studied the distribution of Fos protein-like immunoreactivity in the rat brain after one hour of electrical stimulation of the aortic depressor nerve (ADN). In 13 male Wistar rats under urethane the ADN was cut on both sides and the central ends were placed on stimulating electrodes. Intermittent (11 s on, 6 s off) electrical stimulation at parameters set to elicit a drop in mean arterial pressure of 15–30 mmHg was applied to one, both or neither ADNs for 1 h. CNS sections were incubated for 48 h in anti-Fos antibody and prepared for visualization of the reaction product using the ABC immunoperoxidase technique. Label was found in several discrete brain nuclei primarily on the side ipsilateral to the side of stimulation. In the medulla labelled nuclei were found in the nucleus tractus solitarius, area postrema, rostral and caudal ventrolateral medulla, nucleus ambiguus and medullary reticular formation. In the pons labelled neurons were found in the lateral and ventrolateral parabrachial nucleus, locus coeruleus, pontine reticular field and A 5 region. In the forebrain labelled nuclei were observed in the peri- and paraventricular hypothalamus, supraoptic nucleus, subfornical organ, preoptic area, central nucleus of the amygdala, median preoptic area, horizontal limb of the diagonal band, bed nucleus of the stria terminalis and islands of Calleja. In control animals moderate amounts of label were present in the supraoptic nucleus and periventricular hypothalamus bilaterally. These results define central pathways involved in mediating the baroreceptor reflex.

Influence of direct currents on bone vascular supply.

Electrical stimulation with a DC of 5 microA was found to result in macromolecular leakages in the microcirculation of rabbit metaphyseal bone. The blood flow rate of living bone did not change during 2.5 hours of electrical stimulation. Over a follow-up time of up to 11 weeks it was observed that vessels close to bone borders increased in size and that the number of bone capillaries increased, simultaneous with an increase in bone formation.

Electrical stimulation of sciatic nerve of rats after partial denervation of soleus muscle.

The purpose of this study was to determine the effect of electrical stimulation of the sciatic nerve on the recovery of the weight and tension of partially denervated rat soleus muscle. Electrodes were implanted unilaterally adjacent to the sciatic nerve in 30 adult female Wistar rats. Fifteen rats underwent bilateral partial nerve section (PNS) of the sciatic nerve to stimulate the plantar flexors. Both the normal and partially nerve sectioned animals were stimulated unilaterally with 4 ms, 2-4 mA current given at 10 pulses per second. Groups of five normal and five partially denervated animals were stimulated for two, four or eight hours per day, five days per week for six weeks. The soleus muscles were evaluated for muscle weight (MW), twitch (Pt) and tetanic (Po) tension, contraction time (CT) and fiber areas of the type 1 and type 2 fibers. The MW, Pt, Po, CT and area of the type 1 and 2 muscle fibers of the normal soleus muscles were 114 +/- 15 mg, 21 +/- 4 mg, 95 +/- 20 mg, 95 +/- 21 ms, 1532 +/- 84 microns m2 and 1267 +/- 136 microns m2 respectively. The electrical stimulation had no effect on the normal soleus muscles. The MW, Pt, Po, CT and area of type 1 and 2 muscles fibers of the partially denervated control soleus muscles were 59 +/- 12 mg, 9 +/- 4 mg, 22 +/- 14 mg, 104 +/- 32 ms, 1028 +/- 514 microns m2, and 849 +/- 292 microns m2 respectively. Two hours of electrical stimulation significantly increased the MW (87 +/- 17 g), Pt (17 +/- 6g), and Po (49 +/- 23 g) but not the type 1 and 2 fiber areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Fat and glycogen utilization in the larynx Muscles of fire-bellied toads (Bombina bombina L.) during calling activity.

Both fat and glycogen are present in abundance in the larynx muscles of anurans. To clarify their role, the Musculus dilatator laryngis of the male fire-bellied toad, Bombina bombina was studied. In untreated males, the mean fat content of this larynx muscle was 14%; the muscle contained glycogen amounting to 57% of that measured in the liver tissue of the same animal. After thirteen days of continual calling activity induced by administration of a gonadotropin, the fat content fell to 6%, the glycogen to 34%. The fat content was essentially unchanged (13%) by four hours of electrical stimulation of the muscle; the glycogen content, however, had fallen to 42% after this treatment. Neither component was altered in amount by castration, the fat content being about 13% and that of glycogen, 52%. Nor did treatment with gonadotropic hormone reduce either the fat content (13%) or the amount of glycogen (59%). From these results it was concluded that fats represent a direct source of energy for the larynx muscles, which is used up gradually over long periods of calling. The glycogen in these muscles, on the other hand, is a short-term store sufficient to supply energy for only a few hours of calling activity.

Response of muscle glycogen and phosphorylase to electrical stimulation in trained and nontrained guinea pigs

Total phosphorylase activity determined histochemically was selectively depleted in white fibers of the medial gastrocnemius of adult guinea pigs after 1 hour of electrical stimulation at a frequency of 5/sec. Histochemical depletion of phosphorylase was paralleled by glycogen depletion measured spectrophotometrically in homogenates and histochemically in frozen sections. Every phosphorylase-negative fiber was negative for glycogen as determined by the PAS stain. The number of PAS-negative fibers slightly exceeded the number of phosphorylase-negative fibers. No PAS- and 11 phosphorylase-negative fibers were found in nonstimulated muscles. The histochemical depletion of glycogen and of phosphorylase was more pronounced in the nontrained than in the trained animals.

Influence of sympathetic nerve stimulation on noradrenaline stores in the rat salivary gland

1. During the first hour of electrical stimulation (1 to 20 imp/sec) of the cervical sympathetic chain in rats, a considerable depletion of the noradrenaline content in the submaxillary gland was obtained. 2. Following an impulse-induced depletion, the noradrenaline content recovered at a rate of about 0.5 μg/g/hr. 3. After labeling the adrenergic transmitter stores with noradrenaline-H 3, stimulation caused a reduction in specific noradrenaline activity which was directly related to the stimulation frequency used.