A time-course study of urodynamic analyses in rat models with dopaminergic depletion induced through unilateral and bilateral 6-hydroxydopamine injections.

BACKGROUND: Bladder dysfunction is a common non-motor disorder in Parkinson's disease (PD). This study attempted to determine the bladder dysfunction with disease progression in the PD rat model produced from unilateral/bilateral injections of 6-hydroxydopamine (6-OHDA). METHODS: Cystometrographic (CMG) and external urethral sphincter electromyographic (EUS-EMG) measurements were scheduled in a time-course manner to determine the disease timing, onset, and severity. Animals were allotted into normal control, unilateral, bilateral 6-OHDA injected groups and subjected to scheduled CMG, EUS-EMG analyses at weeks 1, 2, and 4. RESULTS: The urodynamic results concluded that voiding efficiency (VE) was reduced in both unilateral and bilateral PD rats at all-time points. VE had decreased from 57 ± 11% to 31 ± 7% in unilateral PD rats and in bilateral PD rats, a decreased VE of 20 ± 6% was observed compared to control and unilateral PD rats. The EMG results in unilateral PD rats indicated declines in bursting period (BP) (3.78-2.94 s), active period (AP) (93.38-88.75 ms), and silent period (SP) (161.62-114.30 ms). A sudden reduction was noticed in BP (3.62-2.82 s), AP (92.21-86.01 ms), and SP (128.61-60.16 ms) of bilateral PD rats than in control and unilateral PD rats. Histological evidence exhibited a progressive dopaminergic neurons (DA) depletion in the substantia nigra (SN) region in 6-OHDA lesioned rats. CONCLUSION: The experimental outcomes strongly implied that significant variations in bladder function and VE decline were due to the depletion of DA neurons in the SN region of the brain.

Human platelet lysate biotherapy for traumatic brain injury: preclinical assessment.

Traumatic brain injury (TBI) leads to major brain anatomopathological damages underlined by neuroinflammation, oxidative stress and progressive neurodegeneration, ultimately leading to motor and cognitive deterioration. The multiple pathological events resulting from TBI can be addressed not by a single therapeutic approach, but rather by a synergistic biotherapy capable of activating a complementary set of signalling pathways and providing synergistic neuroprotective, anti-inflammatory, antioxidative, and neurorestorative activities. Human platelet lysate might fulfil these requirements as it is composed of a plethora of biomolecules readily accessible as a TBI biotherapy. In the present study, we tested the therapeutic potential of human platelet lysate using in vitro and in vivo models of TBI. We first prepared and characterized platelet lysate from clinical-grade human platelet concentrates. Platelets were pelletized, lysed by three freeze-thaw cycles, and centrifuged. The supernatant was purified by 56°C 30 min heat treatment and spun to obtain the heat-treated platelet pellet lysate that was characterized by ELISA and proteomic analyses. Two mouse models were used to investigate platelet lysate neuroprotective potential. The injury was induced by an in-house manual controlled scratching of the animals' cortex or by controlled cortical impact injury. The platelet lysate treatment was performed by topical application of 60 µl in the lesioned area, followed by daily 60 µl intranasal administration from Day 1 to 6 post-injury. Platelet lysate proteomics identified over 1000 proteins including growth factors, neurotrophins, and antioxidants. ELISA detected several neurotrophic and angiogenic factors at ∼1-50 ng/ml levels. We demonstrate, using two mouse models of TBI, that topical application and intranasal platelet lysate consistently improved mouse motor function in the beam and rotarod tests, mitigated cortical neuroinflammation, and oxidative stress in the injury area, as revealed by downregulation of pro-inflammatory genes and the reduction in reactive oxygen species levels. Moreover, platelet lysate treatment reduced the loss of cortical synaptic proteins. Unbiased proteomic analyses revealed that heat-treated platelet pellet lysate reversed several pathways promoted by both controlled cortical impact and cortical brain scratch and related to transport, postsynaptic density, mitochondria or lipid metabolism. The present data strongly support, for the first time, that human platelet lysate is a reliable and effective therapeutic source of neurorestorative factors. Therefore, brain administration of platelet lysate is a therapeutical strategy that deserves serious and urgent consideration for universal brain trauma treatment.

Effects of paired stimulation with specific waveforms on cortical and spinal plasticity in subjects with a chronic spinal cord injury.

BACKGROUND/PURPOSE: Paired stimulation can cause neuroplasticity in corticospinal and spinal pathways in subjects with a chronic spinal cord injury (SCI). We aimed to know the effects of different waveforms using paired stimulations with bicycling in subjects with a chronic SCI. METHODS: Recruited subjects with an SCI underwent three treatment interventions in random order for 4-20 min followed by 30 min of bicycling (control, repetitive transcranial magnetic stimulation (TMS; rTMS) at 20 Hz with transspinal direct current stimulation (tsDCS), and intermittent theta burst stimulation (iTBS) with tsDCS with a 1-week gap period. A TMS method was employed to record the resting motor threshold (RMT), the 90% values of which was used as the stimulation intensity, and the Hoffman (H)-reflex was measured by stimulating the tibial nerve in the popliteal fossa. The RMT, motor evoked potential (MEP) latency, MEP peak-to-peak amplitude, and H-reflex latency as primary variables and lower extremity motor scale (LEMS) and modified Ashworth spasticity scale (MAS) as secondary variables were analyzed before and after the interventions. RESULTS: The MEP latency, MEP amplitude, and LEMS significantly improved with the rTMS-iTBS/tsDCS or the rTMS-20 Hz/tsDCS (p < 0.050) protocols compared to the control intervention. All other outcome measures, including RMT, H-reflex latency, and MAS score showed some changes but did not fully attain a level of significance. CONCLUSION: The paired stimulation with rTMS-iTBS/tsDCS was equally effective to produce neuroplastic effect in subjects with chronic SCI compared to the conventional TMS-20 Hz/tsDCS intervention.

Safety of Special Waveform of Transcranial Electrical Stimulation (TES): In Vivo Assessment.

Intermittent theta burst (iTBS) powered by direct current stimulation (DCS) can safely be applied transcranially to induce neuroplasticity in the human and animal brain cortex. tDCS-iTBS is a special waveform that is used by very few studies, and its safety needs to be confirmed. Therefore, we aimed to evaluate the safety of tDCS-iTBS in an animal model after brain stimulations for 1 h and 4 weeks. Thirty-one Sprague Dawley rats were divided into two groups: (1) short-term stimulation for 1 h/session (sham, low, and high) and (2) long-term for 30 min, 3 sessions/week for 4 weeks (sham and high). The anodal stimulation applied over the primary motor cortex ranged from 2.5 to 4.5 mA/cm2. The brain biomarkers and scalp tissues were assessed using ELISA and histological analysis (H&E staining) after stimulations. The caspase-3 activity, cortical myelin basic protein (MBP) expression, and cortical interleukin (IL-6) levels increased slightly in both groups compared to sham. The serum MBP, cortical neuron-specific enolase (NSE), and serum IL-6 slightly changed from sham after stimulations. There was no obvious edema or cell necrosis seen in cortical histology after the intervention. The short- and long-term stimulations did not induce significant adverse effects on brain and scalp tissues upon assessing biomarkers and conducting histological analysis.

Motor Neuroplastic Effects of a Novel Paired Stimulation Technology in an Incomplete Spinal Cord Injury Animal Model.

Paired stimulation of the brain and spinal cord can remodel the central nervous tissue circuitry in an animal model to induce motor neuroplasticity. The effects of simultaneous stimulation vary according to the extent and severity of spinal cord injury. Therefore, our study aimed to determine the significant effects on an incomplete SCI rat brain and spinal cord through 3 min and 20 min stimulations after 4 weeks of intervention. Thirty-three Sprague Dawley rats were classified into six groups: (1) normal, (2) sham, (3) iTBS/tsDCS, (4) iTBS/ts-iTBS, (5) rTMS/tsDCS, and (6) rTMS/ts-iTBS. Paired stimulation of the brain cortex and spinal cord thoracic (T10) level was applied simultaneously for 3−20 min. The motor evoked potential (MEP) and Basso, Beattie, and Bresnahan (BBB) scores were recorded after every week of intervention for four weeks along with wheel training for 20 min. Three-minute stimulation with the iTBS/tsDCS intervention induced a significant (p < 0.050 *) increase in MEP after week 2 and week 4 treatments, while 3 min iTBS/ts-iTBS significantly improved MEP (p < 0.050 *) only after the week 3 intervention. The 20 min rTMS/ts-iTBS intervention showed a significant change only in post_5 min after week 4. The BBB score also changed significantly in all groups except for the 20 min rTMS/tsDCS intervention. iTBS/tsDCS and rTMS/ts-iTBS interventions induce neuroplasticity in an incomplete SCI animal model by significantly changing electrophysiological (MEP) and locomotion (BBB) outcomes.

Hemodynamics and Tissue Optical Properties in Bimodal Infarctions Induced by Middle Cerebral Artery Occlusion.

Various infarct sizes induced by middle cerebral artery occlusion (MCAO) generate inconsistent outcomes for stroke preclinical study. Monitoring cerebral hemodynamics may help to verify the outcome of MCAO. The aim of this study was to investigate the changes in brain tissue optical properties by frequency-domain near-infrared spectroscopy (FD-NIRS), and establish the relationship between cerebral hemodynamics and infarct variation in MCAO model. The rats were undergone transient MCAO using intraluminal filament. The optical properties and hemodynamics were measured by placing the FD-NIRS probes on the scalp of the head before, during, and at various time-courses after MCAO. Bimodal infarction severities were observed after the same 90-min MCAO condition. Significant decreases in concentrations of oxygenated hemoglobin ([HbO]) and total hemoglobin ([HbT]), tissue oxygenation saturation (StO2), absorption coefficient (µa) at 830 nm, and reduced scattering coefficient (µs') at both 690 and 830 nm were detected during the occlusion in the severe infarction but not the mild one. Of note, the significant increases in [HbO], [HbT], StO2, and µa at both 690 and 830 nm were found on day 3; and increases in µs' at both 690 and 830 nm were found on day 2 and day 3 after MCAO, respectively. The interhemispheric correlation coefficient (IHCC) was computed from low-frequency hemodynamic oscillation of both hemispheres. Lower IHCCs standing for interhemispheric desynchronizations were found in both mild and severe infarction during occlusion, and only in severe infarction after reperfusion. Our finding supports that sequential FD-NIRS parameters may associated with the severity of the infarction in MCAO model, and the consequent pathologies such as vascular dysfunction and brain edema. Further study is required to validate the potential use of FD-NIRS as a monitor for MCAO verification.

Heat-treated human platelet pellet lysate modulates microglia activation, favors wound healing and promotes neuronal differentiation in vitro.

The neurorestorative efficacy of human platelet lysates in neurodegenerative disorders is still under investigation. Platelets prepared from standard and pathogen reduced platelet concentrates were pelletized, washed, concentrated, and subjected to freeze-thawing. The lysate was heated to 56°C for 30 min and characterized. Toxicity was evaluated using SH-SY5Y neuroblastoma, BV-2 microglial, and EA-hy926 endothelial cells. Inflammatory activity was tested by examining tumor necrosis factor (TNF) and cyclooxygenase (COX)-2 expressions by BV-2 microglia with or without stimulation by lipopolysaccharides (LPS). The capacity to stimulate wound healing was evaluated by a scratch assay, and the capacity to differentiate SH-SY5Y into neurons was also examined. Platelet lysates contained a range of neurotrophins. They were not toxic to SH-SY5Y, EA-hy926, or BV-2 cells, did not induce the expression of TNF or COX-2 inflammatory markers by BV-2 microglia, and decreased inflammation after LPS stimulation. They stimulated the wound closure in the scratch assay and induced SH-SY5Y differentiation as revealed by the increased length of neurites as well as ß3-tubulin and neurofilament staining. These data confirm the therapeutic potential of platelet lysates in the treatment of disorders of the central nervous system and support further evaluation as novel neurorestorative biotherapy in preclinical models.

Early Repetitive Transcranial Magnetic Stimulation Exerts Neuroprotective Effects and Improves Motor Functions in Hemiparkinsonian Rats.

Repetitive transcranial magnetic stimulation (rTMS) is a popular noninvasive technique for modulating motor cortical plasticity and has therapeutic potential for the treatment of Parkinson's disease (PD). However, the therapeutic benefits and related mechanisms of rTMS in PD are still uncertain. Accordingly, preclinical animal research is helpful for enabling translational research to explore an effective therapeutic strategy and for better understanding the underlying mechanisms. Therefore, the current study was designed to identify the therapeutic effects of rTMS on hemiparkinsonian rats. A hemiparkinsonian rat model, induced by unilateral injection of 6-hydroxydopamine (6-OHDA), was applied to evaluate the therapeutic potential of rTMS in motor functions and neuroprotective effect of dopaminergic neurons. Following early and long-term rTMS intervention with an intermittent theta burst stimulation (iTBS) paradigm (starting 24 h post-6-OHDA lesion, 1 session/day, 7 days/week, for a total of 4 weeks) in awake hemiparkinsonian rats, the effects of rTMS on the performance in detailed functional behavioral tests, including video-based gait analysis, the bar test for akinesia, apomorphine-induced rotational analysis, and tests of the degeneration level of dopaminergic neurons, were identified. We found that four weeks of rTMS intervention significantly reduced the aggravation of PD-related symptoms post-6-OHDA lesion. Immunohistochemically, the results showed that tyrosine hydroxylase- (TH-) positive neurons in the substantia nigra pars compacta (SNpc) and fibers in the striatum were significantly preserved in the rTMS treatment group. These findings suggest that early and long-term rTMS with the iTBS paradigm exerts neuroprotective effects and mitigates motor impairments in a hemiparkinsonian rat model. These results further highlight the potential therapeutic effects of rTMS and confirm that long-term rTMS treatment might have clinical relevance and usefulness as an additional treatment approach in individuals with PD.

Transcranial electrostimulation with special waveforms enhances upper-limb motor function in patients with chronic stroke: a pilot randomized controlled trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) and intermittent theta burst stimulation (iTBS) were both demonstrated to have therapeutic potentials to rapidly induce neuroplastic effects in various rehabilitation training regimens. Recently, we developed a novel transcranial electrostimulation device that can flexibly output an electrical current with combined tDCS and iTBS waveforms. However, limited studies have determined the therapeutic effects of this special waveform combination on clinical rehabilitation. Herein, we investigated brain stimulation effects of tDCS-iTBS on upper-limb motor function in chronic stroke patients. METHODS: Twenty-four subjects with a chronic stroke were randomly assigned to a real non-invasive brain stimulation (NIBS; who received the real tDCS + iTBS output) group or a sham NIBS (who received sham tDCS + iTBS output) group. All subjects underwent 18 treatment sessions of 1 h of a conventional rehabilitation program (3 days a week for 6 weeks), where a 20-min NIBS intervention was simultaneously applied during conventional rehabilitation. Outcome measures were assessed before and immediately after the intervention period: Fugl-Meyer Assessment-Upper Extremity (FMA-UE), Jebsen-Taylor Hand Function Test (JTT), and Finger-to-Nose Test (FNT). RESULTS: Both groups showed improvements in FMA-UE, JTT, and FNT scores after the 6-week rehabilitation program. Notably, the real NIBS group had greater improvements in the JTT (p = 0. 016) and FNT (p = 0. 037) scores than the sham NIBS group, as determined by the Mann-Whitney rank-sum test. CONCLUSIONS: Patients who underwent the combined ipsilesional tDCS-iTBS stimulation with conventional rehabilitation exhibited greater impacts than did patients who underwent sham stimulation-conventional rehabilitation in statistically significant clinical responses of the total JTT time and FNT after the stroke. Preliminary results of upper-limb functional recovery suggest that tDCS-iTBS combined with a conventional rehabilitation intervention may be a promising strategy to enhance therapeutic benefits in future clinical settings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04369235. Registered on 30 April 2020.

Effects of interactive video-game-based exercise on balance in older adults with mild-to-moderate Parkinson's disease.

BACKGROUND: This study aimed to evaluate the effectiveness of a customized interactive video game-based (IVGB) training on balance in older adults with mild-to-moderate Parkinson's disease (PD). METHODS: In this 12-week crossover trial, PD patients ≥65 years of age were randomly divided into Group A (a 6-week intervention phase followed by a 6-week control phase) and Group B (a 6-week control phase followed by a 6-week intervention phase). Participants received IVGB exercise training during the intervention phase and no exercise during the control phase. Functional outcomes were measured using behavioral evaluation scales and questionnaires at baseline, week 6 and week 12. RESULTS: Twenty-four PD patients were included in this study, and were evenly divided into two groups. After Bonferroni adjustment, the changes in Modified Falls Efficacy Scale (MFES) and two subscales of Multi-Directional Reach Test were significantly different between two groups in the first 6-week period. In addition, the changes in Berg Balance Scale, MFES, and two subscales of Maximum Step Length were significantly different between two groups in the second 6-week period. Compared to controls, 6-week IVGB exercise intervention significantly improved different but overlapping functional outcomes in two groups of PD patients. CONCLUSIONS: The customized IVGB exercise training improves balance, postural stability and confidence in preventing falls in older adults with mild-to-moderate PD. However, this IVGB exercise doesn't have a significant impact on quality of life. TRIAL REGISTRATION: ClinicalTrials.gov. NCT03689764 . Registered 27 September 2018, retrospectively registered.

Designing and Implementing an Implantable Wireless Micromanometer System for Real-Time Bladder Pressure Monitoring: A Preliminary Study.

Many mini-implantable devices have been developed and fabricated for diagnostic and treatment purposes. Wireless implantable biomicrosystems provide a desirable approach for long-term physiological signal monitoring. In this study, we implemented a wireless implantable biomicrosystem for bladder-cavity pressure measurements in a freely moving rabbit. To manage the power more effectively, a magnetic reed switch was applied to turn on/off the implantable module using a neodymium-iron-boron (NdFeB) magnet. The measured bladder pressure signal was wirelessly transmitted from the implantable module to a host unit. Our results indicated that the implantable biomicrosystem exhibited satisfactory performance and safety, as evidenced by an error percentage of less than ±1% for pressure measurements and less than 2 °C of a temperature rise under normal operation. The wireless biomicrosystem was implanted into the bladder cavity of a rabbit. Bladder pressure was simultaneously measured by both the biomicrosystem and conventional cystometry in the animal. The two signals were similar during the voiding phase, with a correlation coefficient of 0.885. Additionally, the biomicrosystem coated with polydimethylsiloxane in this study showed no cytotoxicity, which confirmed its biocompatibility. In conclusion, we demonstrated a good biocompatible wireless biomicrosystem which showed good reproducibility with respect to pressure monitoring by conventional cystometry. Further studies are needed to confirm the results of this preliminary feasibility study for actual clinical applications.

Neuromodulatory Effects of Transcranial Direct Current Stimulation on Motor Excitability in Rats.

Transcranial direct current stimulation (tDCS) is a noninvasive technique for modulating neural plasticity and is considered to have therapeutic potential in neurological disorders. For the purpose of translational neuroscience research, a suitable animal model can be ideal for providing a stable condition for identifying mechanisms that can help to explore therapeutic strategies. Here, we developed a tDCS protocol for modulating motor excitability in anesthetized rats. To examine the responses of tDCS-elicited plasticity, the motor evoked potential (MEP) and MEP input-output (IO) curve elicited by epidural motor cortical electrical stimulus were evaluated at baseline and after 30 min of anodal tDCS or cathodal tDCS. Furthermore, a paired-pulse cortical electrical stimulus was applied to assess changes in the inhibitory network by measuring long-interval intracortical inhibition (LICI) before and after tDCS. In the results, analogous to those observed in humans, the present study demonstrates long-term potentiation- (LTP-) and long-term depression- (LTD-) like plasticity can be induced by tDCS protocol in anesthetized rats. We found that the MEPs were significantly enhanced immediately after anodal tDCS at 0.1 mA and 0.8 mA and remained enhanced for 30 min. Similarly, MEPs were suppressed immediately after cathodal tDCS at 0.8 mA and lasted for 30 min. No effect was noted on the MEP magnitude under sham tDCS stimulation. Furthermore, the IO curve slope was elevated following anodal tDCS and presented a trend toward diminished slope after cathodal tDCS. No significant differences in the LICI ratio of pre- to post-tDCS were observed. These results indicated that developed tDCS schemes can produce consistent, rapid, and controllable electrophysiological changes in corticomotor excitability in rats. This newly developed tDCS animal model could be useful to further explore mechanical insights and may serve as a translational platform bridging human and animal studies, establishing new therapeutic strategies for neurological disorders.

Effects of pulsed-radiofrequency neuromodulation on the rat with overactive bladder.

AIM: To quantify the effects of pulsed radiofrequency (PRF) electrical stimulations of the pudendal and pelvic nerves on the bladder function of rats with detrusor overactivity. METHODS: All rats were pretreated with a continuous transvesical infusion of 0.5% acetic acid (AA) for inducing detrusor overactivity. Intravesical pressure was recorded using cysometrography (CMG) during the continuous transvesical infusion to examine the effects of PRF electrical stimulation of the pudendal and pelvic nerves individually. In addition, the activity of caspase-3, an apoptosis marker, in the pelvic nerve was examined to evaluate the impact of PRF on nerve injury. RESULTS: According to the first CMG recording, AA treatment significantly reduced bladder capacity (BC) and intercontraction interval (ICI) to 65% and 66% of the corresponding control values, respectively. Subsequently, PRF electrical stimulation of the pelvic nerve inhibited AA-induced detrusor overactivity and significantly increased BC to approximately 102-110% and ICI to 79-92%; these effects persisted for at least 4 h. Furthermore, PRF did not cause significant neural damage to the target stimulated nerves, as demonstrated by caspase-3 activity. CONCLUSION: PRF electrical stimulation of pelvic nerves exerted a long-lasting effect of suppressing AA-induced detrusor overactivity. This modality can be used as an alternative approach for improving bladder continence in patients with overactive bladder syndrome.

Does pharmacological activation of 5-HT1A receptors improve urine flow rate in female rats?

The role of 5-HT1A receptors in regulating voiding functions remains unclear, particularly regarding the urine flow rate (UFR) during voiding. This study examined the effects of 5-HT1A receptors on regulating urethral functions in female rats and investigated underlying modulatory mechanisms. Intravesical pressure (IVP), external urethral sphincter-electromyography (EUS-EMG), and UFR were simultaneously recorded during continuous transvesical infusion to examine the effects of a 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635) on bladder and urethral functions. In addition, this study evaluated the independent roles of urethral striated and smooth muscles in the UFR in rats after a neuromuscular blockade (NMB) treatment and bilateral hypogastric nerve transection. Our results revealed that 8-OH-DPAT significantly increased the maximal UFR but reduced the mean UFR. This discrepancy may be because 8-OH-DPAT markedly increased the maximal UFR during the initial segment of the flow duration and subsequently induced an approximately zero level of long oscillatory waves during the remaining flow duration. Thus the mean UFR was reduced because of the prolonged approximately zero level of the UFR. However, paralyzing the EUS with an NMB agent, 8-OH-DPAT, significantly increased the maximal and mean UFRs because the prolonged zero level of the oscillatory UFR did not continue. These results support the hypothesis that the increased UFR in female rats during voiding is due to the induction of urethral smooth muscle relaxation by 8-OH-DPAT. This paper provides a detailed understanding of the role of 5-HT1A receptors in controlling the UFR in female rats.

Effects of pudendal neuromodulation on bladder function in chronic spinal cord-injured rats.

BACKGROUND/PURPOSE: Few studies have investigated the feasibility of using pudendal neuromodulation to regulate bladder function in spinal cord-injured (SCI) animals. The present study aimed to determine the effects of electrical activation of the pudendal sensory branch on improving voiding functions in rats 6 weeks after a spinal cord injury and to explore the underlying neuromodulatory mechanisms. METHODS: Two urodynamic measurements were used to assess the effects of electrical stimulation (ES) on bladder and urethral functions: simultaneous recordings of the intravesical pressure (IVP) during continuous isotonic transvesical infusion (i.e., isotonic IVP) and external urethral sphincter (EUS) electromyography (EUS-EMG), and simultaneous recordings of transvesical pressure under isovolumetric conditions (i.e., isovolumetric IVP) and urethral perfusion pressure (UPP). RESULTS: Six weeks after the SCI, the rats showed voiding dysfunction, as indicated by abnormal cystometric measurements (e.g., increased volume threshold, increased contraction amplitude, and increased residual volume, and decreased voided volume). The voiding efficiency (VE) decreased to 13% after the SCI, but increased to 22-34% after applying pudendal afferent stimulation. In addition, pudendal stimulation significantly increased the EUS burst period and increased the difference between the UPP and the high-frequency oscillation (HFO) baselines, and changed the time offset between bladder and EUS activities. These findings suggest that pudendal afferent stimulation improved the VE by prolonging the micturition interval, decreased the urethral resistance, and recovered detrusor-sphincter dyssynergia during the voiding phase. CONCLUSION: This study demonstrates the feasibility of using pudendal neuromodulation in chronic SCI rats. These results could aid in developing an advanced neural prosthesis to restore bladder function in clinical settings.

Design and evaluation of potentiometric principles for bladder volume monitoring: a preliminary study.

Recent advances in microelectronics and wireless transmission technology have led to the development of various implantable sensors for real-time monitoring of bladder conditions. Although various sensing approaches for monitoring bladder conditions were reported, most such sensors have remained at the laboratory stage due to the existence of vital drawbacks. In the present study, we explored a new concept for monitoring the bladder capacity on the basis of potentiometric principles. A prototype of a potentiometer module was designed and fabricated and integrated with a commercial wireless transmission module and power unit. A series of in vitro pig bladder experiments was conducted to determine the best design parameters for implementing the prototype potentiometric device and to prove its feasibility. We successfully implemented the potentiometric module in a pig bladder model in vitro, and the error of the accuracy of bladder volume detection was <±3%. Although the proposed potentiometric device was built using a commercial wireless module, the design principles and animal experience gathered from this research can serve as a basis for developing new implantable bladder sensors in the future.

Influence of serotonergic mechanisms on the urine flow rate in male rats.

This study extensively examined the role of a 5-HT(1A) receptor in controlling voiding function in anesthetized male rats. A simultaneous recording of the intravesical pressure (IVP), external urethral sphincter (EUS)-electromyography (EMG), and urine flow rate (UFR) during continuous cystometry was used. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a 5-HT(1A) receptor agonist, significantly improved the voiding efficiency, as detected by increases in the evoked contraction amplitude, EUS burst period, and silent period, and decreases in the volume threshold, pressure threshold, and residual volume. Interestingly, the UFR during voiding was reduced by 8-OH-DPAT, as evidenced by decreases in the maximal UFR and mean UFRs of the voiding period, spike duration, and interspike interval. Conversely, treating rats with WAY-100635, a 5-HT(1A) antagonist, produced effects opposite to those produced by 8-OH-DPAT. These findings suggest that 8-OH-DPAT improved the voiding efficiency by enhancing the detrusor contractile ability and prolonging EUS burst period, which would compensate for the lower UFR, resulting from urethral smooth muscle contractions and longer EUS silent periods during voiding. The present study contributes to our understanding of the role of 5-HT(1A) receptors in controlling the urine flow rate in male rats.

Fibrous hydrogel scaffolds with cells embedded in the fibers as a potential tissue scaffold for skin repair.

A novel approach was undertaken to create a potential skin wound dressing. L929 fibroblast cells and alginate solution were simultaneously dispensed into a calcium chloride solution using a three-dimensional plotting system to manufacture a fibrous alginate scaffold with interconnected pores. These cells were then embedded in the alginate hydrogel fibers of the scaffold. A conventional scaffold with cells directly seeded on the fiber surface was used as a control. The encapsulated fibroblasts made using the co-dispensing method distributed homogeneously within the scaffold and showed the delayed formation of large cell aggregates compared to the control. The cells embedded in the hydrogel fibers also deposited more type I collagen in the extracellular matrix and expressed higher levels of fgf11 and fn1 than the control, indicating increased cellular proliferation and attachment. The results indicate that the novel co-dispensing alginate scaffold may promote skin regeneration better than the conventional directly-seeded scaffold.

Multi-Modal Sleep Stage Classification With Two-Stream Encoder-Decoder.

Sleep staging serves as a fundamental assessment for sleep quality measurement and sleep disorder diagnosis. Although current deep learning approaches have successfully integrated multimodal sleep signals, enhancing the accuracy of automatic sleep staging, certain challenges remain, as follows: 1) optimizing the utilization of multi-modal information complementarity, 2) effectively extracting both long- and short-range temporal features of sleep information, and 3) addressing the class imbalance problem in sleep data. To address these challenges, this paper proposes a two-stream encode-decoder network, named TSEDSleepNet, which is inspired by the depth sensitive attention and automatic multi-modal fusion (DSA2F) framework. In TSEDSleepNet, a two-stream encoder is used to extract the multiscale features of electrooculogram (EOG) and electroencephalogram (EEG) signals. And a self-attention mechanism is utilized to fuse the multiscale features, generating multi-modal saliency features. Subsequently, the coarser-scale construction module (CSCM) is adopted to extract and construct multi-resolution features from the multiscale features and the salient features. Thereafter, a Transformer module is applied to capture both long- and short-range temporal features from the multi-resolution features. Finally, the long- and short-range temporal features are restored with low-layer details and mapped to the predicted classification results. Additionally, the Lovász loss function is applied to alleviate the class imbalance problem in sleep datasets. Our proposed method was tested on the Sleep-EDF-39 and Sleep-EDF-153 datasets, and it achieved classification accuracies of 88.9% and 85.2% and Macro-F1 scores of 84.8% and 79.7%, respectively, thus outperforming conventional traditional baseline models. These results highlight the efficacy of the proposed method in fusing multi-modal information. This method has potential for application as an adjunct tool for diagnosing sleep disorders.

Effects of Strengthening Exercises on Human Kinetic Chains Based on a Systematic Review.

Kinetic chains (KCs) are primarily affected by the load of different activities that recruit muscles from different regions. We explored the effects of strengthening exercises on KCs through muscle activation. Four databases were searched from 1990 to 2019. The muscles of each KC, their surface electromyography (sEMG), and the exercises conducted were reported. We found 36 studies that presented muscle activation using the percent (%) maximal voluntary isometric contraction (MVIC) or average sEMG for nine KCs in different regions. The % MVIC is presented as the following four categories: low (≤20%), moderate (21~40%), high (41~60%), and very high (>60%). Only four studies mentioned muscle activation in more than three KCs, while the remaining studies reported inconsistent sEMG processing, lacked normalization, and muscle activation in one or two KCs. The roles of stabilizers and the base of support in overhead throwing mobility using balance exercises were examined, and the concentric phase of chin-up and lat pull-down activated the entire KC by recruiting multiple muscles. Also, deep-water running was shown to prevent the risk of falls and enhance balance and stability. In addition, low-load trunk rotations improved the muscles of the back and external oblique activation. Based on this study's findings, closed-chain exercises activate more groups of muscles in a kinetic chain than open-chain exercises. However, no closed or open chain exercise can activate optimal KCs.