Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor loss.Previous research supports the beneficial effect of electrical stimulation on photoreceptor survival.This study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal degeneration.Additionally,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem humans.In this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp waveforms.To investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with age.Human retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in vitro.Photoreceptor density was evaluated by rhodopsin immunolabeling.In vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp waveforms.Retinal function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),respectively.Immunolabeling was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse retinas.Oscilloscope recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest voltage.Evaluation of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human eyes.The temperature recordings during and after electrical stimulation indicated no significant temperature change in vivo and only a subtle temperature increase in vitro(~0.5-1.5°C).Electrical stimulation increased photoreceptor survival in human retinal explant cultures,particularly at the ramp waveform.Transcorneal electrical stimulation(rectangular+ramp)waveforms significantly improved the survival and function of S and M-cones and enhanced visual acuity based on the optomotor response results.Histology and immunolabeling demonstrated increased photoreceptor survival,improved outer nuclear layer thickness,and increased bipolar cell sprouting in Rho^(-/-)mice.These results indicate that transcorneal electrical stimulation effectively delivers the electrical field to the retina,improves photoreceptor survival in both human and mouse retinas,and increases visual function in Rho^(-/-)mice.Combined rectangular and ramp waveform stimulation can promote photoreceptor survival in a minimally invasive fashion.

Safety and effectiveness of neuromuscular electrical stimulation in cardiac surgery:A systematic review

BACKGROUND Lack of mobilization and prolonged stay in the intensive care unit(ICU)are major factors resulting in the development of ICU-acquired muscle weakness(ICUAW).ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery,and may be a risk factor for prolonged duration of mechanical ventilation,associated with a higher risk of readmission and higher mortality.Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay.Neuromuscular electrical stimulation(NMES)is an alternative modality of exercise in patients with muscle weakness.A major advantage of NMES is that it can be applied even in sedated patients in the ICU,a fact that might enhance early mobilization in these patients.AIM To evaluate safety,feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery.METHODS We performed a search on Pubmed,Physiotherapy Evidence Database(PEDro),Embase and CINAHL databases,selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials(RCTs)that included implementation of NMES in patients before after cardiac surgery.RCTs were assessed for methodological rigor and risk of bias via the PEDro.The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function.RESULTS Ten studies were included in our systematic review,resulting in 703 participants.Almost half of them performed NMES and the other half were included in the control group,treated with usual care.Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery.Functional capacity was assessed in 8 studies via 6MWT or other indices,and improved only in 1 study before and in 1 after cardiac surgery.Nine studies explored the effects of NMES on muscle strength and function and,most of them,found increase of muscle strength and improvement in muscle function after NMES.NMES was safe in all studies without any significant complication.CONCLUSION NMES is safe,feasible and has beneficial effects on muscle strength and function in patients after cardiac surgery,but has no significant effect on functional capacity.

Effect of percutaneous electrical stimulation at the Baliao point on preventing postpartum urinary retention after labor analgesia

BACKGROUND Anesthetic drugs used in labor analgesia also paralyze the bladder muscle by blocking the sacral plexus,thereby affecting maternal postpartum spontaneous urination and increasing the risk of postpartum urinary retention(PUR).AIM To analyze the effect of percutaneous electrical stimulation at the Baliao point combined with biofeedback therapy for PUR prevention.METHODS We selected 182 pregnant women who received labor analgesia in obstetrics between June 2022 and December 2023.They were divided into the combined therapy group(transcutaneous electrical stimulation of the Baliao point combined with biofeedback therapy)and the control group(biofeedback therapy alone).The first spontaneous urination time,first postpartum urine volume,bladder residual urine volume,postpartum hemorrhage volume,pre-urination waiting time,PUR incidence,adverse reactions,and the intervention’s clinical efficacy were compared between the two groups.RESULTS The first spontaneous urination time after delivery was more delayed(2.92±1.04 h vs 3.61±1.13 h,P<0.001),with fewer initial postpartum urine(163.54±24.67 mL vs 143.72±23.95 mL,P<0.001),more residual bladder urine(54.81±10.78 mL vs 65.25±13.52 mL,P<0.001),more postpartum bleeding(323.15±46.95 mL vs 348.12±45.03 mL,P=0.001),and longer waiting time for urination(0.94±0.31 min vs 1.29±0.42 min,P<0.001),in the control group than in the combined therapy group.The control group also had higher PUR incidence(4.65%vs 15.85%,P=0.016).Both groups had no adverse reactions,but the clinical total efficacy rate of the intervention was significantly higher in the combined therapy group than in the control group(95.35%vs 84.15%,P=0.016).CONCLUSION Percutaneous electrical stimulation of the Baliao point combined with biofeedback can significantly promote postpartum micturition of parturients with labor analgesia,thereby effectively preventing PUR occurrence.

Impact of transcranial electrical stimulation on serum neurotrophic factors and language function in patients with speech disorders

BACKGROUND Speech disorders have a substantial impact on communication abilities and quality of life.Traditional treatments such as speech and psychological therapies frequently demonstrate limited effectiveness and patient compliance.Transcranial electrical stimulation(TES)has emerged as a promising non-invasive treatment to improve neurological functions.However,its effectiveness in enhancing language functions and serum neurofactor levels in individuals with speech disorders requires further investigation.AIM To investigate the impact of TES in conjunction with standard therapies on serum neurotrophic factor levels and language function in patients with speech disorders.METHODS In a controlled study spanning from March 2019 to November 2021,81 patients with speech disorders were divided into a control group(n=40)receiving standard speech stimulation and psychological intervention,and an observation group(n=41)receiving additional TES.The study assessed serum levels of ciliary neurotrophic factor(CNTF),glial cell-derived neurotrophic factor(GDNF),brainderived neurotrophic factor(BDNF),and nerve growth factor(NGF),as well as evaluations of motor function,language function,and development quotient scores.RESULTS After 3 wk of intervention,the observation group exhibited significantly higher serum levels of CNTF,GDNF,BDNF,and NGF compared to the control group.Moreover,improvements were noted in motor function,cognitive function,language skills,physical abilities,and overall development quotient scores.It is worth mentioning that the observation group also displayed superior perfor CONCLUSION This retrospective study concluded that TES combined with traditional speech and psychotherapy can effectively increase the levels of neurokines in the blood and enhance language function in patients with speech disorders.These results provide a promising avenue for integrating TES into standard treatment methods for speech disorders.

Analysis on the Effect of Yiqi Huoxue Decoction Combined with Neuromuscular Electrical Stimulation in Improving ICU-Acquired Debility in Mechanically Ventilated Patients

Objective:To investigate the effect of Yiqi Huoxue decoction combined with neuromuscular electrical stimulation on improving intensive care unit(ICU)acquired debility in mechanically ventilated patients.Methods:50 patients who were admitted to the ICU and received mechanical ventilation treatment in our hospital from June 2022 to June 2023 and were complicated with ICU-acquired neurasthenia were selected,and randomly grouped using the randomized envelope method into two groups:control group with 25 patients who received neuromuscular electrical stimulation alone;observation group with 25 patients who received the traditional Chinese medicine Yiqi Huoxue decoction.Comparison indexes:treatment efficiency,degree of emotional recovery(APACHEⅡscore),muscle strength status(MRC score),motor status(FAC rating),and self-care ability(BI index score).Results:The treatment efficiency of patients in the observation group patients was higher as compared to those in the control group(P<0.05).There was no significant difference in the comparison of the results of the scores(ratings)of each index between the two groups before treatment(P>0.05).After the treatment,the APACHEⅡscores of patients in the observation group were significantly lower as compared to those in the control group,while the MRC scores,FAC ratings,and BI index scores were higher in the observation group than those of the control group patients(P<0.05).Conclusion:The combined application of Yiqi Huoxue decoction and neuromuscular electrical stimulation in the treatment of patients with ICU-acquired neurasthenia complicated by mechanical ventilation significantly enhanced the clinical efficacy,the patient’s muscle strength,motor status,and ability of self-care.Hence,it has high application value and is worthy to be popularized.

Safety and effectiveness of electromyography-induced rehabilitation treatment after epidural electrical stimulation for spinal cord injury:study protocol for a prospective,randomized,controlled trial

Epidural electrical stimulation is a new treatment method for spinal cord injury(SCI).Its efficacy and safety have previously been reported.Rehabilitation treatment after epidural electrical stimulation is important to ensure and improve the postoperative efficacy of epidural electrical stimulation in patients with SCI.Considering that electromyography(EMG)-induced rehabilitation treatment can accurately match the muscle contraction of patients with SCI,we designed a study protocol for a prospective,randomized controlled trial.In this trial,on the premise of adjusting the spinal cord electrical stimulator to obtain the maximum EMG signal of the target muscle,patients with SCI receiving epidural electrical stimulation will undergo EMG-induced rehabilitation treatment.Recovery of muscle strength of key muscles,quality of life,safety and therapeutic effects will be monitored.Twenty patients with SCI who are scheduled to undergo epidural electrical stimulation in Shanghai Ruijin Rehabilitation Hospital will be randomly divided into two groups with 10 patients per group.The control group will receive conventional rehabilitation treatment.The EMG-induced rehabilitation group will receive EMG-induced rehabilitation treatment of the target muscles of the upper and lower limbs based on conventional rehabilitation treatment.After rehabilitation treatment,follow up for all patients will occur at 2 weeks and 1,3 and 6 months.The primary outcome measure of this trial will be evaluation of target muscle recovery using the Manual Muscle Testing grading scale.Secondary outcome measures will include modified Barthel Index scores,integrated EMG values,the visual analogue scale,Spinal Cord Independence Measure scores,and modified Ashworth scale scores.The safety indicator will be the incidence of adverse events.This trial will collect data regarding the therapeutic effects of EMG-induced rehabilitation in patients with SCI receiving epidural electrical stimulation for 6 months after rehabilitation treatment.Findings from this trial will help develop rehabilitation methods in patients with SCI after epidural electrical stimulation.This study protocol was approved by Ethics Committee of Shanghai Ruijin Rehabilitation Hospital(Approval No.RKIRB2022-12)on February 15,2022 and was registered with Chinese Clinical Trial Registry(registration number:ChiCTR2200061674;date:June 30,2022).Study protocol version:1.0.

E®ect of laser acupuncture combined with electrical stimulation on recovery from exercise fatigue in mice

In sports events,the rapid recovery after high-intensity training or sport competition performance is very important for athletes'performance and health.The aim of this study is to evaluate the effect of laser acupuncture and electrical stimulation on the recovery from exercise fatigue,using mice with swimming fatigue as experimental model and the electromyography(EMG)and the Raman spectroscopy of blood as evaluation indicators.Root mean square(RMS)and mean power frequency(MPF)of EMG were analyzed after laser acupuncture and electrical stimulation.The amplitude frequency combined analysis(JASA)showed that the proportion of muscles in the fatigue recovery area of the control group,the laser acupuncture group,the multi-channel laser acupuncture group and the laser combined with electrical stimulation group were 34.78%,39.13%,39.13%and 43.48%,respectively.Raman spectroscopy of the mice blood during fatigue recovery showed there is a significant difference between the multi-channel laser acupuncture group and the laser combined with electric stimulation group compared with the recovery period and fatigue period(P<0:05)at the peak of 997 cm^(-1) and the laser combined electrical stimulation group had a statistical difference in the recovery period compared with the fatigue period(P<0.05)at the peak of 1561 cm^(-1).The results showed that laser acupuncture combined with electrical stimulation was beneficial to fatigue recovery in mice,and had the potential value in sports fatigue recovery.

Treatment of postpartum depression with integrated traditional Chinese and Western medicine nursing and electrical stimulation

BACKGROUND Postpartum depression(PPD)is a common psychological disease among puerperal women,and postpartum pelvic floor dysfunction is a common disease among pregnant women.The occurrence of postpartum pelvic floor dysfunction will increase the incidence of PPD.AIM To explore the therapeutic effect of integrated traditional Chinese and Western medicine nursing combined with electrical stimulation of pelvic floor muscles and the rectus abdominis on PPD.METHODS From April 2020 to January 2022,100 parturients with a rectus abdominis muscle separation distance>2.0 cm who underwent reexamination 6 wk after delivery at our hospital were selected as the research subjects.According to the random number table method,the patients were divided into either an observation group(n=50)or a control group(n=50).There was no significant difference in the general data between the two groups(P>0.05).Both groups were treated by electrical stimulation.The observation group was additionally treated by integrated traditional Chinese and Western medicine nursing.A self-designed Depression Knowledge Questionnaire was used to evaluate the awareness of knowledge on depression in all patients 3 wk after intervention.The Hamilton Depression Scale(HAMD)was used to evaluate the depression before intervention and 1 wk and 3 wk after intervention,and the Morisky Medication Adherence Scale(MMAS-8)was used to evaluate the medication compliance.SPSS19.0 was used for statistical analyses.RESULTS The rate of awareness of knowledge on depression in the observation group was significantly higher than that of the control group(P<0.05).The scores of MMAS-8 were comparable between the two groups before intervention(P>0.05),but were significantly higher in the observation group than in the control group at 1 wk and 3 wk after intervention(P<0.05).The HAMD scores were comparable between the two groups before intervention(P>0.05),but were significantly lower in the observation group than in the control group at 1 wk and 3 wk after intervention(P<0.05).CONCLUSION Integrated traditional Chinese and Western medicine nursing combined with electrical stimulation of pelvic floor muscles and the rectus abdominis is effective in the treatment of postpartum depression and worthy of clinical promotion.

Effects of Neuromuscular Electrical Stimulation in Combination with Glutamine Administration on Skeletal Muscle Atrophy in Colon-26 Tumor-Bearing Mice

The depressed protein synthetic response,a phenomenon termed anabolic resistance,has been shown to be involved in muscle wasting induced by cancer cachexia.Moreover,a positive relationship between the protein synthetic rate and intracellular glutamine(GLN)concentration has been found in skeletal muscles.This study investigated the effects of neuromuscular electrical stimulation(ES)and GLN administration on muscle wasting and GLN metabolism in colon-26(C-26)tumor-bearing mice.CD2F1 mice were divided into 8 groups:control(CNT),CNT+ES,CNT+GLN,CNT+ES+GLN,C-26,C-26+ES,C-26+GLN,C-26+ES+GLN.Cancer cachexia was induced by subcutaneous injection of C-26 cells and developed for four weeks.ES was performed on the left plantar flexor muscles every other day,and GLN(1 g/kg)was administered daily intraperitoneally starting one day after the C-26 injection.Tumor-free body mass and fast-twitch gastrocnemius(Gas)muscle weight were lower in the C-26 group than in the CNT group(-19%and-17%,respectively).Neither ES training nor GLN administration,alone or in combination,ameliorated the loss of Gas muscle weight in the C-26 mice.However,ES training in combination with GLN administration inhibited the increased expression of GLN synthetase(GS)in the C-26 muscles.Thus,it is likely that GLN plays a critical role in muscle protein metabolism and,therefore,can be targeted as a tentative treatment of cancer cachexia.

Neuronal apoptosis in cerebral ischemia/reperfusion area following electrical stimulation of fastigial nucleus

Previous studies have indicated that electrical stimulation of the cerebellar fastigial nucleus in rats may reduce brain infarct size, increase the expression of Ku70 in cerebral ischemia/ reperfusion area, and decrease the number of apoptotic neurons. However, the anti-apoptotic mechanism of Ku70 remains unclear. In this study, fastigial nucleus stimulation was given to rats 24, 48, and 72 hours before cerebral ischemia/reperfusion injury. Results from the electrical stim- ulation group revealed that rats exhibited a reduction in brain infarct size, a significant increase in the expression of KuT0 in cerebral ischemia/reperfusion regions, and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL）-positive cells. Double immunofluorescence staining revealed no co-localization of Ku70 with TUNEL-positive cells. However, Ku70 partly co-localized with Bax protein in the cytoplasm of rats with cerebral ischemia/reperfusion injury. These findings suggest an involvement of Ku70 with Bax in the cy- toplasm of rats exposed to electrical stimulation of the cerebellar fastigial nucleus, and may thus provide an understanding into the anti-apoptotic activity of KuT0 in cerebral ischemia/reperfu- sion injury.

Resuscitation therapy for traumatic brain injuryinduced coma in rats:mechanisms of median nerve electrical stimulation

In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually in-creased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our ifndings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the pre-frontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.

Functional electrical stimulation-facilitated proliferation and regeneration of neural precursor cells in the brains of rats with cerebral infarction

Previous studies have shown that proliferation of endogenous neural precursor cells cannot alone compensate for the damage to neurons and axons. From the perspective of neural plastici- ty, we observed the effects of functional electrical stimulation treatment on endogenous neural precursor cell proliferation and expression of basic fibroblast growth factor and epidermal growth factor in the rat brain on the infarct side. Functional electrical stimulation was performed in rat models of acute middle cerebral artery occlusion. Simultaneously, we set up a placebo stimulation group and a sham-operated group. Immunohistochemical staining showed that, at 7 and 14 days, compared with the placebo group, the numbers of nestin （a neural precursor cell marker）-positive cells in the subgranular zone and subventricular zone were increased in the functional electrical stimulation treatment group. Western blot assays and reverse-transcription PCR showed that total protein levels and gene expression of epidermal growth factor and basic fibroblast growth factor were also upregulated on the infarct side. Prehensile traction test results showed that, at 14 days, prehension function of rats in the functional electrical stimulation group was significantly better than in the placebo group. These results suggest that functional electrical stimulation can promote endogenous neural precursor cell proliferation in the brains of acute cerebral infarction rats, enhance expression of basic fibroblast growth factor and epidermal growth factor, and improve the motor function of rats.

Intervention effect of neuromuscular electrical stimulation on ICU acquired weakness: A meta-analysis

Objective:The early use of neuromuscular electrical stimulation(NMES)to prevent intensive care unit-acquired weakness(ICU-AW)in critical patients is still a controversial topic.We conducted a systematic review to clarify the effectiveness of NMES in preventing ICU-AW.Methods:The Cochrane Library,PubMed,EMBASE,MEDUNE,Web of Science,Ovid,CNKI,Wanfang,VIP,China Biology Medicine disc(CBMdisc)and other databases were searched for randomized controlled trials on the influence of NMES on ICU-AW.The studies were selected according to the inclusion and exclusion criteria.After data and quality were evaluated,a meta-analysis was performed by RevMan 5.3 software.Results:A total of 11 randomized controlled trials with 576 patients were included.The meta-analysis results showed that NMES can improve muscle strength[MD=1.78,95%CI(0.44,3.12,P=0.009);shorten the mechanical ventilation(MV)time[SMD=-0.65,95%CI(-1.03,-0.27,P=0.001],ICU length of stay[MD=-3.41,95%CI(-4.58,-4.24),P<0.001],and total length of stay[MD=-3.97,95%CI(-6.89,-1.06,P=0.008];improve the ability of patients to perform activities of daily living[SMD=0.9,95%CI(0.45,1.35),P=0.001];and increase walking distance[MD=239.03,95%CI(179.22298.85),P<0.001].However,there is no evidence indicating that NMES can improve the functional status of ICU patients during hospitalization,promote the early awakening of patients or reduce mortality(P>0.05).Conclusion:Early implementation of the NMES intervention in ICU patients can prevent ICU-AW and improve their quality of life by enhancing their muscle strength and shortening the MV duration,length of stay in the ICU and total length of stay in the hospital.

Combination therapy using evening primrose oil and electrical stimulation to improve nerve function following a crush injury of sciatic nerve in male rats

Peripheral nerve injuries with a poor prognosis are common.Evening primrose oil（EPO） has beneficial biological effects and immunomodulatory properties.Since electrical activity plays a major role in neural regeneration,the present study investigated the effects of electrical stimulation（ES）,combined with evening primrose oil（EPO）,on sciatic nerve function after a crush injury in rats.In anesthetized rats,the sciatic nerve was crushed using small haemostatic forceps followed by ES and/or EPO treatment for 4 weeks.Functional recovery of the sciatic nerve was assessed using the sciatic functional index.Histopathological changes of gastrocnemius muscle atrophy were investigated by light microscopy.Electrophysiological changes were assessed by the nerve conduction velocity of sciatic nerves.Immunohistochemistry was used to determine the remyelination of the sciatic nerve following the interventions.EPO ＋ ES,EPO,and ES obviously improved sciatic nerve function assessed by the sciatic functional index and nerve conduction velocity of the sciatic nerve at 28 days after operation.Expression of the peripheral nerve remyelination marker,protein zero（P0）,was increased in the treatment groups at 28 days after operation.Muscle atrophy severity was decreased significantly while the nerve conduction velocity was increased significantly in rats with sciatic nerve injury in the injury ＋ EPO ＋ ES group than in the EPO or ES group.Totally speaking,the combined use of EPO and ES may produce an improving effect on the function of sciatic nerves injured by a crush.The increased expression of P0 may have contributed to improving the functional effects of combination therapy with EPO and ES as well as the electrophysiological and histopathological features of the injured peripheral nerve.

Electrical stimulation does not enhance nerve regeneration if delayed after sciatic nerve injury: the role of fibrosis

Electrical stimulation has been shown to accelerate and enhance nerve regeneration in sensory and motor neurons after injury, but there is little evidence that focuses on the varying degrees of fibrosis in the delayed repair of peripheral nerve tissue. In this study, a rat model of sciatic nerve transec- tion injury was repaired with a biodegradable conduit at 1 day, 1 week, 1 month and 2 months after injury, when the rats were divided into two subgroups. In the experimental group, rats were treated with electrical stimuli of frequency of 20 Hz, pulse width 100 ms and direct current voltage of 3 V; while rats in the control group received no electrical stimulation after the conduit operation. His- tological results showed that stained collagen fibers comprised less than 20% of the total operated area in the two groups after delayed repair at both 1 day and 1 week but after longer delays, the collagen fiber area increased with the time after injury. Immunohistochemical staining revealed that the expression level of transforming growth factor ~ （an indicator of tissue fibrosis） decreased at both 1 day and 1 week after delayed repair but increased at both 1 and 2 months after delayed repair. These findings indicate that if the biodegradable conduit repair combined with electrical stimulation is delayed, it results in a poor outcome following sciatic nerve injury. One month after injury, tissue degeneration and distal fibrosis are apparent and are probably the main reason why electrical stimulation fails to promote nerve regeneration after delayed repair.

Basic mechanisms of peripheral nerve injury and treatment via electrical stimulation

Previous studies on the mechanisms of peripheral nerve injury(PNI)have mainly focused on the pathophysiological changes within a single injury site.However,recent studies have indicated that within the central nervous system,PNI can lead to changes in both injury sites and target organs at the cellular and molecular levels.Therefore,the basic mechanisms of PNI have not been comprehensively understood.Although electrical stimulation was found to promote axonal regeneration and functional rehabilitation after PNI,as well as to alleviate neuropathic pain,the specific mechanisms of successful PNI treatment are unclear.We summarize and discuss the basic mechanisms of PNI and of treatment via electrical stimulation.After PNI,activity in the central nervous system(spinal cord)is altered,which can limit regeneration of the damaged nerve.For example,cell apoptosis and synaptic stripping in the anterior horn of the spinal cord can reduce the speed of nerve regeneration.The pathological changes in the posterior horn of the spinal cord can modulate sensory abnormalities after PNI.This can be observed in cases of ectopic discharge of the dorsal root ganglion leading to increased pain signal transmission.The injured site of the peripheral nerve is also an important factor affecting post-PNI repair.After PNI,the proximal end of the injured site sends out axial buds to innervate both the skin and muscle at the injury site.A slow speed of axon regeneration leads to low nerve regeneration.Therefore,it can take a long time for the proximal nerve to reinnervate the skin and muscle at the injured site.From the perspective of target organs,long-term denervation can cause atrophy of the corresponding skeletal muscle,which leads to abnormal sensory perception and hyperalgesia,and finally,the loss of target organ function.The mechanisms underlying the use of electrical stimulation to treat PNI include the inhibition of synaptic stripping,addressing the excessive excitability of the dorsal root ganglion,alleviating neuropathic pain,improving neurological function,and accelerating nerve regeneration.Electrical stimulation of target organs can reduce the atrophy of denervated skeletal muscle and promote the recovery of sensory function.Findings from the included studies confirm that after PNI,a series of physiological and pathological changes occur in the spinal cord,injury site,and target organs,leading to dysfunction.Electrical stimulation may address the pathophysiological changes mentioned above,thus promoting nerve regeneration and ameliorating dysfunction.

Epidural electrical stimulation for spinal cord injury

A long-standing goal of spinal cord injury research is to develop effective repair strategies,which can restore motor and sensory functions to near-normal levels.Recent advances in clinical management of spinal cord injury have significantly improved the prognosis,survival rate and quality of life in patients with spinal cord injury.In addition,a significant progress in basic science research has unraveled the underlying cellular and molecular events of spinal cord injury.Such efforts enabled the development of pharmacologic agents,biomaterials and stem-cell based therapy.Despite these efforts,there is still no standard care to regenerate axons or restore function of silent axons in the injured spinal cord.These challenges led to an increased focus on another therapeutic approach,namely neuromodulation.In multiple animal models of spinal cord injury,epidural electrical stimulation of the spinal cord has demonstrated a recovery of motor function.Emerging evidence regarding the efficacy of epidural electrical stimulation has further expanded the potential of epidural electrical stimulation for treating patients with spinal cord injury.However,most clinical studies were conducted on a very small number of patients with a wide range of spinal cord injury.Thus,subsequent studies are essential to evaluate the therapeutic potential of epidural electrical stimulation for spinal cord injury and to optimize stimulation parameters.Here,we discuss cellular and molecular events that continue to damage the injured spinal cord and impede neurological recovery following spinal cord injury.We also discuss and summarize the animal and human studies that evaluated epidural electrical stimulation in spinal cord injury.

Bridging peripheral nerves using a deacetyl chitin conduit combined with short-term electrical stimulation

Previous studies have demonstrated that deacetyl chitin conduit nerve bridging or electrical stimulation can effectively promote the regeneration of the injured peripheral nerve. We hypoth-esized that the combination of these two approaches could result in enhanced regeneration. Rats with right sciatic nerve injury were subjected to deacetyl chitin conduit bridging combined with electrical stimulation （0.1 ms, 3 V, 20 Hz, for 1 hour）. At 6 and 12 weeks after treatment, nerve conduction velocity, myelinated axon number, ifber diameter, axon diameter and the thickness of the myelin sheath in the stimulation group were better than in the non-stimulation group. The results indicate that deacetyl chitin conduit bridging combined with temporary electrical stimu-lation can promote peripheral nerve repair.

Electrical stimulation of the sacral nerve anterior root following induced bladder detrusor contraction

The sacral nerve anterior root consists of parasympathetic nerves（dominating urinary bladder detrusor）and somatic motor nerves（dominating urethral sphincter）,and electrical stimulation to the sacral nerve anterior root induces simultaneous contraction of the bladder detrusor and urethral sphincter.Accordingly,urethral pressure exceeds intravesical pressure,resulting in little or no urination,kidney damage,and trembling of lower limbs due to high intravesical pressure.In the present study,sacral nerve posterior roots were transected in a spastic bladder rabbit model,followed by three-pole electrode and long-pulse electrical stimulation to the sacral anterior root.Intravesical and urethral pressures were simultaneously measured to verify the feasibility of anode inhibition to the sacral anterior root following induced detrusor contraction.As stimulus intensity increased,somatic motor nerves were increasingly inhibited; with a stimulus pulse width of 300 μs and stimulus current of 1.05 mA,urethral pressure was zero and average intravesical pressure was 3.84 kPa.In addition,detrusor contraction was displayed,and lower extremity trembling was significantly reduced.Three-pole electrode and long-pulse electrical stimulation to the sacral nerve anterior root induced detrusor contraction and inhibited low extremity trembling under electrical stimulation.

A novel functional electrical stimulation-control system for restoring motor function of post-stroke hemiplegic patients

Hemiparesis is one of the most common consequences of stroke. Advanced rehabilitation techniques are essential for restoring motor function in hemiplegic patients. Functional electrical stimulation applied to the affected limb based on myoelectric signal from the unaffected limb is a promising therapy for hemiplegia. In this study, we developed a prototype system for evaluating this novel functional electrical stimulation-control strategy. Based on surface electromyography and a vector machine model, a self-administered, muki-movement, force-modulation functional electrical stimulation-prototype system for hemiplegia was implemented. This paper discusses the hardware design, the algorithm of the system, and key points of the self-oscillation-prone system. The experimental results demonstrate the feasibility of the prototype system for further clinical trials, which is being conducted to evaluate the efficacy of the proposed rehabilitation technique.