Electrical Stimulation Research Articles

Transcutaneous Auricular Vagus Nerve Stimulation for Visually Induced Motion Sickness: An eLORETA Study

Transcutaneous auricular vagus nerve stimulation (taVNS), a non-invasive form of electrical brain stimulation, has shown potent therapeutic potential for a wide spectrum of conditions. How taVNS influences the characterization of motion sickness – a long mysterious syndrome with a polysymptomatic onset – remains unclear. Here, to examine taVNS-induced effects on brain function in response to motion-induced nausea, 64-channel electroencephalography (EEG) recordings from 42 healthy participants were analyzed; collected during nauseogenic visual stimulation concurrent with taVNS administration, in a crossover randomized sham-controlled study. Cortical neuronal generators were estimated from the obtained EEG using exact low-resolution brain electromagnetic tomography (eLORETA). While both sham and taVNS increased insula activation during electrical stimulation, compared to baseline, taVNS additionally augmented middle frontal gyrus neuronal activity. Following taVNS, brain regions including the supramarginal, parahippocampal, and precentral gyri were activated. Contrasting sham, taVNS markedly increased activity in the middle occipital gyrus during stimulation. A repeated-measures ANOVA showed that taVNS reduced motion sickness symptoms. This reduction in symptoms correlated with taVNS-induced neural activation. Our findings provide new insights into taVNS-induced brain changes, during and after nauseogenic stimuli exposure, including accompanying behavioral response. Together, these findings suggest that taVNS has promise as an effective neurostimulation tool for motion sickness management.

Distinct Ventral Hippocampus Network Properties inDissociated Cultures.

Extensive research has been focused in the past century on structural, physiological, and molecular attributes of the hippocampus. This interest was created by the unique involvement of the hippocampus in cognitive and affective functions of the brain. Functional analysis revealed that the hippocampus has divergent properties along its axial dimension to the extent that the dorsal sector (dorsal hippocampus, DH) has different connections with the rest of the brain than those of the ventral sector (VH). Still, longitudinal pathways connect the DH with the VH and dampen the functional differences between the sectors. To be able to identify the intrinsic functional difference between the DH and VH, we produced dissociated monolayer cultures from prenatal DH and VH and examined their properties at 10-20 days after plating by imaging the spontaneous activity of the network using Fluo-2 AM, a calcium indicator. Surprisingly, while DH and VH sectors produced dissociated cultures with similar morphological attributes, VH cultures were more active spontaneously than DH cultures. Furthermore, when stimulated to produce action potentials, VH neurons triggered network bursts in postsynaptic neurons more often than DH cultures. Finally, in both DH and VH cultures, electrical stimulation of single cells produced network bursts in response to a burst of action potentials rather than to single spikes. These experiments indicate that even in dissociated cultures, neurons of the VH are more excitable and sensitive to electrical stimulation than DH; hence, they are more likely to generate network bursts and epileptic seizures, as suggested for invivo brains.

DELirium treatment with Transcranial Electrical Stimulation (DELTES): study protocol for a multicentre, randomised, double-blind, sham-controlled trial.

Delirium, a clinical manifestation of acute encephalopathy, is associated with extended hospitalisation, long-term cognitive dysfunction, increased mortality and high healthcare costs. Despite intensive research, there is still no targeted treatment. Delirium is characterised by electroencephalography (EEG) slowing, increased relative delta power and decreased functional connectivity. Recent studies suggest that transcranial alternating current stimulation (tACS) can entrain EEG activity, strengthen connectivity and improve cognitive functioning. Hence, tACS offers a potential treatment for augmenting EEG activity and reducing the duration of delirium. This study aims to evaluate the feasibility and assess the efficacy of tACS in reducing relative delta power. A randomised, double-blind, sham-controlled trial will be conducted across three medical centres in the Netherlands. The study comprises two phases: a pilot phase (n=30) and a main study phase (n=129). Participants are patients aged 50 years and older who are diagnosed with delirium using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria (DSM-5-TR), that persists despite treatment of underlying causes. During the pilot phase, participants will be randomised (1:1) to receive either standardised (10 Hz) tACS or sham tACS. In the main study phase, participants will be randomised to standardised tACS, sham tACS or personalised tACS, in which tACS settings are tailored to the participant. All participants will undergo daily 30 min of (sham) stimulation for up to 14 days or until delirium resolution or hospital discharge. Sixty-four-channel resting-state EEG will be recorded pre- and post the first tACS session, and following the final tACS session. Daily delirium assessments will be acquired using the Intensive Care Delirium Screening Checklist and Delirium Observation Screening Scale. The pilot phase will assess the percentage of completed tACS sessions and increased care requirements post-tACS. The primary outcome variable is change in relative delta EEG power. Secondary outcomes include (1) delirium duration and severity, (2) quantitative EEG measurements, (3) length of hospital stay, (4) cognitive functioning at 3 months post-tACS and (5) tACS treatment burden. Study recruitment started in April 2024 and is ongoing. The study has been approved by the Medical Ethics Committee of the Utrecht University Medical Center and the Institutional Review Boards of all participating centres. Trial results will be disseminated via peer-reviewed publications and conference presentations. NCT06285721.

Comparison of anti-gravity treadmill training and traditional treadmill training in patients with moderate to severe knee osteoarthritis: A randomized controlled trial.

Aerobic exercise is recommended to alleviate pain and protect the joint for patients with advanced knee osteoarthritis, however, its clinical implementation is challenging due to the potential for exacerbating pain. The study aimed to compare the effects of anti-gravity treadmill training with traditional treadmill training in patients with advanced knee osteoarthritis. This single-blinded randomized-controlled trial included 30 women with knee osteoarthritis. All participants received hotpack, transcutaneous electrical nerve stimulation, and therapeutic ultrasound. Additionally, group 1 received anti-gravity treadmill, while group 2 received traditional treadmill training. Group 3 served as the control. The interventions were administered three-times a week for eight-weeks. The visual analogue scale (VAS) pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), six-minute-walk-test distance (6MWD), and femoral cartilage thickness were evaluated at baseline and weeks 4 and 8. VAS-pain significantly reduced over time in both anti-gravity (P < 0.001) and control (P = 0.004) groups. The anti-gravity group also showed significant improvements in WOMAC-pain (P = 0.008), WOMAC-total (P = 0.048), and 6MWD (P < 0.001). Post-hoc analysis indicated significant time (P < 0.001, effect size, ηp2 = 0.682) and interaction (P = 0.006, ηp2 = 0.271) effects on VAS, with no significant between-group differences. Femoral cartilage thickness showed no significant between-group differences, except within-group differences in the treadmill group (P = 0.037). Anti-gravity treadmill training significantly improved pain, functionality, and functional capacity in patients with knee osteoarthritis, while traditional treadmill resulted in a reduction in femoral cartilage thickness. Further research should investigate long-term outcomes and more diverse populations. NCT05319964.

Nociceptive electrical stimulation increases mean arterial blood pressure without an evident electroencephalographic response in dogs anesthetized with sevoflurane

Nociceptive electrical stimulation increases mean arterial blood pressure without an evident electroencephalographic response in dogs anesthetized with sevoflurane

Efficacy of gastric per-oral endoscopic myotomy remains similar after failure of interventional techniques in refractory gastroparesis

Background and aimsGastric per-oral endoscopic myotomy (G-POEM) is a new therapeutic option for the treatment of refractory gastroparesis. However, the outcome of G-POEM after the failure of gastric electrical stimulation (GES) or other pylorus-targeting therapies has been poorly reported. MethodsData were collected from patients referred for G-POEM for refractory gastroparesis. The efficacy in patients with previous interventional techniques was compared to patients naïve to instrumental technique. The primary endpoint was the 6-month clinical success rate, defined as at least a 1-point decrease in the Gastroparesis Cardinal Symptom Index (GCSI). ResultsAmong 48 patients referred for G-POEM, 32 patients had had previous instrumental treatments (66%): 15 (31%) had had GES, and 17 (35%) had had pyloric endoscopic dilation or toxin injection. The technical success rate was 100%. At 6 months, clinical success was achieved in 25/48 patients (52%) and the GCSI decreased from 3.38 (2.94–3.95) to 2.25 (1.11–3.36) (p < 0.001). The 6-month success rate was similar in patients with or without previous instrumental treatment (50.0% vs 56.3%; p = 0.41). The complication rate was also similar in the two groups (6.3% vs 12.5%; p = 0.59), with only one severe adverse event. The only predictive factor for success at 6 months was a higher body mass index (OR = 1.14 [1.01–1.32]; p = 0.05). ConclusionG-POEM is safe and remains effective after GES or previous pyloric treatment failure, with 50% efficacy at 6 months. The therapeutic strategy in refractory gastroparesis remains to be defined.

The effect of abdominal functional electrical stimulation on blood pressure in people with high level spinal cord injury.

Single centre training study. To investigate, in a group of people with spinal cord injury (SCI), the effect of transcutaneous functional electrical stimulation of the abdominal muscles (abdominal FES) during cough training on blood pressure (BP), and how it is affected by injury characteristics and alters over time. Laboratory and community. Sixteen participants with SCI (C4-T5) underwent 25 of abdominal FES cough training (5 sets of 10 stimulated coughs) over 6 weeks as part of a previously published study on the effect of abdominal FES training on cough. Systolic BP (SBP), diastolic BP (DBP) and calculated mean arterial pressure (MAP) were measured at the completion of each set. Abdominal FES coughing resulted in an average ~30% acute increase in BP from initial resting BP across all sessions in almost all participants (p < 0.001). However, the increase in BP during abdominal FES coughs from rest reduced over the 25 sessions of training by ~35% for SBP, MAP and DBP (p = 0.024, p = 0.013 and p = 0.042, respectively). There was no meaningful change in resting BP over time (p = 0.935, p = 0.705 and p = 0.988, respectively). Overall, increases in BP during abdominal FES coughs were greatest for those with chronic injuries and cervical injuries. Transcutaneous abdominal FES during cough training acutely increases BP. However, the magnitude of the increase is reduced after 25 sessions of training. Abdominal FES may offer a solution to combat orthostatic hypotension, but its effectiveness may diminish over time.

Relationship between Apoptosis Induction in Cancer Cells and the Amount of Electrical Stimulation on Frequency Analysis of Nanosecond Pulsed Electric Field

Relationship between Apoptosis Induction in Cancer Cells and the Amount of Electrical Stimulation on Frequency Analysis of Nanosecond Pulsed Electric Field

Characterising the contribution of auditory and somatosensory inputs to TMS-evoked potentials following stimulation of prefrontal, premotor, and parietal cortex

Abstract Transcranial magnetic stimulation (TMS) results in a series of deflections in electroencephalography (EEG) recordings known as a TMS-evoked potential (TEP). However, it remains unclear whether these responses reflect neural activity resulting from transcranial stimulation of the cortex, the sensory experiences of TMS, or a combination of the two. Across three experiments (total n = 135), we recorded EEG activity following TMS to the dorsolateral prefrontal cortex, premotor cortex, and parietal cortex as well as a sensory control condition (stimulation of the shoulder or electrical stimulation of the scalp with a click sound). We found that TEPs showed a stereotypical frontocentral N100/P200 complex following TMS of all cortical sites and control conditions, regardless of TMS intensity or the type of sensory control. In contrast, earlier TEPs (&amp;lt;60 ms) showed site-specific characteristics which were largest at the site of stimulation, although TEP topographies were distorted in a subgroup of individuals due to residual TMS-evoked muscle artefact despite cleaning with independent component analysis. Self-reported sensory experiences differed across sites, with prefrontal stimulation resulting in stronger auditory (click sound perception) and somatosensory input (scalp muscle twitch, discomfort) than premotor or parietal stimulation, a pattern that was reflected in the amplitude of later (N100/P200), but not earlier (&amp;lt;60 ms), TEP peak amplitudes. Later TEPs were also larger in individuals who experienced stronger click sound perception and, to a lesser extent, TMS-evoked scalp muscle twitches. Increasing click sound perception by removing auditory masking increased N100/P200 amplitudes without altering earlier peaks, an effect which was more prominent at sites with more successful masking. Together, these findings suggest that the frontocentral N100/P200 complex primarily represents a generalised sensory response resulting from TMS-related auditory and somatosensory input when present. In contrast, early TEP peaks likely primarily reflect activity resulting from transcranial stimulation of the cortex when artefacts were adequately accounted for. The results have important implications for designing and interpreting TEP studies, especially when comparing TEPs between stimulation sites and participant groups showing differences in sensory experiences following TMS.

Pain-Discriminating Information Decoded From Spatiotemporal Patterns of Hemodynamic Responses Measured by fMRI in the Human Brain.

Functional magnetic resonance imaging (fMRI) has been widely used in studying the neural mechanisms of pain in the human brain, primarily focusing on where in the brain pain-elicited neural activities occur (i.e., the spatial distribution of pain-related brain activities). However, the temporal dynamics of pain-elicited hemodynamic responses (HDRs) measured by fMRI may also contain information specific to pain processing but have been largely neglected. Using high temporal resolution fMRI (TR = 0.8 s) data acquired from 62 healthy participants, in the present study we aimed to test whether pain-distinguishing information could be decoded from the spatial pattern of the temporal dynamics (i.e., the spatiotemporal pattern) of HDRs elicited by painful stimuli. Specifically, the peak latency and the response duration were used to characterize the temporal dynamics of HDRs to painful laser stimuli and non-painful electric stimuli, and then were compared between the two conditions (i.e., pain and no-pain) using a voxel-wise univariate analysis and a multivariate pattern analysis. Furthermore, we also tested whether the two temporal characteristics of pain-elicited HDRs and their spatial patterns were associated with pain-related behaviors. We found that the spatial patterns of HDR peak latency and response duration could successfully discriminate pain from no-pain. Interestingly, we also observed that the Pain Vigilance and Awareness Questionnaire (PVAQ) scores were correlated with the average response duration in bilateral insula and secondary somatosensory cortex (S2) and could also be predicted from the across-voxel spatial patterns of response durations in the middle cingulate cortex and middle frontal gyrus only during painful condition but not during non-painful condition. These findings indicate that the spatiotemporal pattern of pain-elicited HDRs may contain pain-specific information and highlight the importance of studying the neural mechanisms of pain by taking advantage of the high sensitivity of fMRI to both spatial and temporal information of brain responses.

Restorative Treatments for Cervical Spinal Cord Injury, a Narrative Review.

A narrative review. To summarize relevant data from representative studies investigating upper limb restorative therapies for cervical spinal cord injury. Cervical spinal cord injury (SCI) is a debilitating condition resulting in tetraplegia, lifelong disability, and reduced quality of life. Given the dependence of all activities on hand function, patients with tetraplegia rank regaining hand function as one of their highest priorities. Recovery from cervical SCI is heterogeneous and often incomplete; currently, various novel therapies are under investigation to improve neurological function and eventually better quality of life in patients with tetraplegia. In this article, a narrative literature review was performed to identify treatment options targeting the restoration of function in patients with cervical SCI. Studies were included from available literature based on the availability of clinical data and whether they are applicable to restoration of arm and hand function in patients with cervical SCI. We describe relevant studies including indications and outcomes with a focus on arm and hand function. Different treatment modalities described include nerve transfers, tendon transfers, spinal cord stimulation, functional electrical stimulation, non-invasive brain stimulation, brain-machine interfaces and neuroprosthetics, stem cell therapy, and immunotherapy. As the authors' institution leads one of the largest clinical trials on nerve transfers for cervical SCI, we also describe how patients undergoing nerve transfers are managed and followed at our center. While complete recovery from cervical spinal cord injury may not be possible, novel therapies aimed at the restoration of upper limb motor function have made significant progress toward the realization of complete recovery.

Flight power muscles have a coordinated, causal role in hawkmoth pitch turns.

Flying insects solve a daunting control problem of generating a patterned and precise motor program to stay airborne and generate agile maneuvers. In this motor program, each muscle encodes information about movement in precise spike timing down to the millisecond scale. Whereas individual muscles share information about movement, we do not know if they have separable effects on an animal's motion, or if muscles functionally interact such that the effects of any muscle's timing depend heavily on the state of the entire musculature. To answer these questions, we performed spike-resolution electromyography and electrical stimulation in the hawkmoth Manduca sexta during tethered flapping. We specifically explored how flight power muscles contribute to pitch control. Combining correlational study of visually-induced turns with causal manipulation of spike timing, we discovered likely coordination patterns for pitch turns, and investigated if these patterns can drive pitch control. We observed significant timing change of the main downstroke muscles, the dorsolongitudinal muscles (DLMs), associated with pitch turns. Causally inducing this timing change in the DLMs with electrical stimulation produced a consistent, mechanically relevant feature in pitch torque, establishing that power muscles in Manduca have a control role in pitch. Because changes were evoked in only the DLMs, however, these pitch torque features left large unexplained variation. We find this unexplained variation indicates significant functional overlap in pitch control such that precise timing of one power muscle does not produce a precise turn, demonstrating the importance of coordination across the entire motor program for flight.

Can Offset Analgesia Magnitude Provide Additional Information About Endogenous Pain Modulation in People With Knee Osteoarthritis? An Experimental Study.

To investigate the relationship between offset analgesia magnitude and the responsiveness to conditioned pain modulation (CPM), temporal summation of (second) pain (TSP), and clinical pain severity in people with knee osteoarthritis (KOA). Electrical stimuli were applied to 88 participants with KOA to measure offset analgesia at the volar forearm of the dominant hand, and CPM and TSP at the most symptomatic knee and ipsilateral volar wrist. Clinical pain severity was assessed using the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOSPAIN). Linear mixed effects models evaluated pain modulatory effects across all tests, and Spearman's partial correlations assessed associations between offset analgesia, CPM, TSP, and KOOSPAIN while accounting for covariates of interest. Participants unable to validly finish all psychophysical tests were excluded from effect and correlation analyses but were evaluated for predictors of non-valid completion using bivariate Stochastic Search Variable Selection. Significant pain modulation was observed across all psychophysical tests (P < 0.05) and no meaningful predictors of non-valid test completion were found. Offset analgesia magnitude did not significantly correlate with CPM, TSP, or KOOSPAIN (p ≥ 0.05), with a maximum partial correlation coefficient of ρ = 0.21. Offset analgesia was not associated with CPM, TSP, or KOOSPAIN in people with KOA. Despite the lack of case-control studies comparing offset analgesia between people with KOA and healthy controls, these findings suggest that offset analgesia may provide information about endogenous pain modulation beyond CPM and TSP, though its clinical translation remains uncertain.

Conditional deletion of IP3R1 by Islet1-Cre in mice reveals a critical role of IP3R1 in interstitial cells of Cajal in regulating GI motility.

Inositol 1,4,5-trisphosphate receptor type 1 (IP3R1) has been proposed to play a physiological role in regulating gastrointestinal (GI) motility, but the underlying cell-dependent mechanism remains unclear. Here, we utilized cell-specific IP3R1 deletion strategies to address this question in mice. Conditional IP3R1 knockout mice using Wnt1-Cre, Islet1-Cre mice, and smMHC-CreEGFP were generated. Cell lineage tracing was performed to determine where gene deletion occurred in the GI tract. Whole-gut transit assay and isometric tension recording were used to assess GI function in vivo and in vitro. In the mouse GI tract, Islet1-Cre targeted smooth muscle cells (SMCs) and interstitial cells of Cajal (ICCs), but not enteric neurons. IP3R1 deletion by Islet1-Cre (isR1KO) caused a phenotype of intestinal pseudo-obstruction (IPO), evidenced by prolonged whole-gut transit time, enlarged GI tract, abdominal distention, and early lethality. IP3R1 deletion by Islet1-Cre not only reduced the frequency of spontaneous contractions but also decreased the contractile responses to the muscarinic agonist carbachol (CCh) and electrical field stimulation (EFS) in colonic circular muscles. By contrast, smMHC-CreEGFP only targeted SMCs in the mouse GI tract. Although IP3R1 deletion by smMHC-CreEGFP (smR1KO)also reduced the contractile responses to CCh and EFS in colonic circular muscles, the frequency of spontaneous contractions was less affected, and neither global GI abnormalities nor early lethality was found in smR1KO mice. IP3R1 deletion in both ICCs and SMCs but not in SMCs alone causes an IPO phenotype, suggesting that IP3R1 in ICCs plays an essential role in regulating GI motility in vivo.

OPTIMIZING THE PHYSICAL DEVELOPMENT OF ADULTS BY USING EMS FITNESS TECHNOLOGY IN LEISURE TIME MOTOR ACTIVITIES

EMS Fitness is an electrical muscle stimulation, a full-body training method that offers the combination of strength training and cardio training through a machine that uses electrical impulses to stimulate muscle contraction. The aim of the study was to follow the effects of electrostimulation training on body composition, weight loss and muscle strength increase. Ten people, women and men, aged between 25 and 50, were studied. We want to demonstrate the hypothesis that the use of the EMS Fitness technique over a period of 90 days will lead to a decrease in body weight, optimisation of body mass index and increase in muscle strength. Participants in the exercise group performed 12 weeks of high-intensity training using specific EMS equipment in an Xbody. The objective of the experiment was to identify whether the use of EMS technology contributed to changes in body mass, skeletal muscle mass, body fat and visceral fat. All exercise sessions were constantly supervised; in addition, exercise intensity, volume and frequency were recorded in training logs. A body composition scale was used for testing, which provides accurate body analysis using BIA technology. The training scheme was used for 12 weeks, changing the dosage and intensity for each subject, with the first signs of weight loss appearing after the first week. Methods used in the research: experimental method, graph-tabel method, observation method, bibliographic study method. Our results support the hypothesis, as the use of the EMS Fitness technique over a period of 90 days led to decreased body mass, optimized body mass index and increased muscle strength. In conclusion, I believe that people in Romania should have a wider openness in practicing physical exercise in their free time in order to develop a healthy generation and decrease the possibility of reaching the stage of obesity and stopping diseases, and a good help in achieving this goal is presented by training using EMS Fitness technology.

Effect of Atomoxetine on Mouse Isolated Vas Deferens Contractility

Objective: Atomoxetine (ATX), a selective noradrenaline re-uptake inhibitor, is a preferred drug with sufficient efficacy and favorable safety profile for the treatment of attention-deficit hyperactivity disorder. Ejaculatory dysfunctions have been reported in the patients receiving ATX as sexual side effect, of which underlying mechanisms are largely unknown. The present study aimed to investigate the effect of ATX on mouse isolated vas deferens (VD) contractility as a potential mechanism of ATX-induced ejaculatory dysfunction. Material and Methods: Isolated organ bath studies were performed on prostatic parts of VD obtained from adult male Balb/c mice. The effect of ATX (10-6, 10-5, 3x10-5 and 10-4 M) on KCl (80 mM), phenylephrine (PhE, 3x10-4 M), adenosine 5’-triphosphate (ATP, 10-2 M) and electrical field stimulation (EFS; 100 V, 64 Hz)-induced contractions of VD strips were evaluated in concentration dependent manner. Results: ATX at 10-6 and 10-5 did not alter the contractile responses (p&gt;0.05), however, higher concentrations of ATX (3x10-5 or 10-4 M) significantly inhibited the KCl, PhE, ATP and EFS-induced contractions of VD strips (p&lt;0.05). Conclusion: The present study demonstrated for the first time that ATX decreased the contractile responses of mouse isolated VD concentration-dependently. Our results suggest that ejaculatory dysfunction might be related to the inhibitory effect on ATX on VD.

A translational approach for understanding hyperalgesia: What has the high-frequency electrical stimulation model taught us?

High-frequency electrical stimulation (HFS) of C fiber nociceptors induces long-term potentiation (LTP) at the first spinal synapse. This spinal LTP is believed to play a role in the amplification of pain. However, the effects of HFS are probably not restricted to the spinal cord. A recent study showed that HFS increases cortical responses to noxious stimuli in a porcine model. Are these increased cortical responses a correlate of spinal LTP and do we observe the same in humans?

Synergistic effects of human umbilical cord mesenchymal stem cells/neural stem cells and epidural electrical stimulation on spinal cord injury rehabilitation

Spinal cord injury (SCI) is a severe neurological condition marked by a complex pathology leading to irreversible functional loss, which current treatments fail to improve. Epidural electrical stimulation (EES) shows promise in alleviating pathological pain, regulating hemodynamic disturbances, and enhancing motor function by modulating residual interneurons in the lower spinal cord. Cell transplantation (CT), especially using human umbilical cord mesenchymal stem cells (hUCMSCs) and neural stem cells (NSCs), has significantly improved sensory and motor recovery in SCI. However, the limitations of single treatments have driven the exploration of a multifaceted strategy, combining various modalities to optimize recovery at different stages. To comprehensively investigate the effectiveness of in situ transplantation of hUCMSCs/NSCs combined with subacute epidural electrical stimulation in a murine spinal cord crush injury model, providing valuable references for future animal studies and clinical research. In this study, we first examined neural stem cell changes via mRNA sequencing in an in vitro Transwell co-culture model. We then explored cell interaction mechanisms using proliferation assays, differentiation assays, and neuron complexity analysis. For animal experiments, 40 C57BL/6 mice were assigned to four groups (Injury/EES/CT/Combination). Histological evaluations employed HE and immunofluorescence staining, while electrophysiological and behavioral tests assessed motor recovery. Quantitative data were reported as mean ± standard error, with statistical analyses performed using GraphPad Prism and SPSS. Initially, we found that NSCs in the in vitro co-culture model showed a unique expression profile of differentially expressed genes (DEGs) compared to controls. GO/KEGG analysis indicated these DEGs were mainly linked to cell differentiation and growth factor secretion pathways. Neuronal and astrocytic markers further confirmed enhanced NSC differentiation and neuronal maturation in the co-culture model. In vivo, live imaging and human nuclei immunofluorescence staining revealed that transplanted cells persisted for some time post-transplantation. Histological analysis showed that during acute inflammation, both the stem cell and combined therapy groups significantly inhibited microglial polarization. In the chronic phase, these groups reduced fibrotic scar formation and encouraged astrocytic bridging. Behavioral tests, including swimming and gait analysis, demonstrated that combined CT and EES therapy was more effective than either treatment alone. In summary, the combined therapy offers a promising approach for spinal cord injury treatment, providing superior outcomes over individual treatments. Our findings underscore the potential of a combined treatment approach utilizing stem cells transplantation and EES as an effective strategy for the comprehensive management of spinal cord crush injury in mice. This integrated approach holds promise for enhancing functional recovery and improving the quality of life for individuals with spinal cord injury (SCI).

Are tinnitus burden and tinnitus exacerbation after cochlear implantation influenced by insertion technique, array dislocation, and intracochlear trauma?

IntroductionAlthough numerous studies suggest that cochlear implantation (CI) generally alleviates the overall burden of tinnitus, certain patients experience tinnitus exacerbation following CI. The exact cause of this exacerbation is still uncertain. This prospective study aimed to investigate whether cochlear trauma, resulting from scalar dislocation of the electrode array, affected postoperative tinnitus intensity, tinnitus burden, and speech perception. Additionally, the influence of CI insertion technique, insertion depth, insertion angle, and cochlear morphology on postoperative tinnitus was assessed.MethodsWe evaluated 66 CI recipients preoperatively at 2 days, 4 weeks, and 12- and 24-months following surgery. Digital volume tomography was employed to document scalar position, insertion depth, and cochlear morphology postoperatively. Speech perception was analyzed using Freiburg monosyllables. The tinnitus burden was evaluated using the tinnitus questionnaire, while the tinnitus intensity was quantified using a visual analog scale.ResultsStudy results pertaining to tinnitus intensity and burden did not reveal a significant difference in elevation regarding scalar position and dislocation after CI surgery compared to preoperative tinnitus levels. However, dislocation was only identified in four patients, and scala vestibuli insertions were observed in two patients. Comparing preoperative and 1-year postoperative outcomes, CI was noted to substantially reduce the tinnitus burden. When the speech processor was worn, the tinnitus intensity was significantly diminished. In comparison to round window (RW) insertion, the insertion technique cochleostomy (CS) did not exhibit a significant difference or a trend toward increased tinnitus intensity.ConclusionThis study demonstrates that CI significantly decreases the tinnitus burden. The observation implies that the electrical stimulation of the auditory pathway, facilitated by wearing the speech processor, significantly reduced the tinnitus intensity. The incidence of dislocations and scala vestibuli insertions has declined to the extent that it is no longer feasible to formulate statistically significant conclusions.

High Antimicrobial Electrotherapy and Wound Monitoring Hydrogel with Bimetal Phenolic Networks for Smart Healthcare

AbstractThe design and fabrication of novel soft bioelectronic materials for rapid wound healing and real‐time monitoring are critical for smart healthcare. However, developing such integrated multifunctional materials devices remains challenging due to fabrication dynamics and sensing interface issues. Herein, a novel strategy is presented for accelerating the kinetics of hydrogels integrating antimicrobial, electrotherapeutic, and wound monitoring functions via bimetallic phenolic networks. The Al3+ catalyzes the radical copolymerization reaction of acrylic acid, resulting in the gelation of the system within 10 s, and also catalyzes the redox reaction between silver and lignin, inducing the sustained release of catechol, which significantly enhances the hydrogel's antimicrobial activity and shortened the wound healing process. Meanwhile, the abundant non‐covalent interactions enhance the hydrogel's tissue adhesion, and mechanical properties (tensile strength 1.558 MPa and elongation 1563%). In addition, the bimetallic ions endow the hydrogels with excellent sensing properties. Under the synergy of electrical stimulation, the wound healing rate is accelerated. Notably, wound assessment can be performed by monitoring changes in electrical signals over the wound, which can assist physicians and patients in achieving intelligent wound management. This work provides new insights into the design and application of multifunctional smart bioelectronic materials.