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.

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.

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.

Evaluating neuromuscular electrical stimulation for preventing and managing intensive care unit-acquired weakness:Current evidence and future directions

Intensive care unit-acquired weakness(ICU-AW)is a prevalent issue in critical care,leading to significant muscle atrophy and functional impairment.Aiming to address this,Neuromuscular Electrical Stimulation(NMES)has been explored as a therapy.This systematic review assesses NMES's safety and effectiveness in enhancing functional capacity and mobility in pre-and post-cardiac surgery patients.NMES was generally safe and feasible,with intervention sessions varying in frequency and duration.Improvements in muscle strength and 6-minute walking test distances were observed,particularly in preoperative settings,but postoperative benefits were inconsistent.NMES showed promise in preventing muscle loss and improving strength,although its impact on overall functional capacity remained uncertain.Challenges such as short ICU stays and body composition affecting NMES efficacy were noted.NMES also holds potential for other conditions like cerebral palsy and stroke.Further research is needed to optimize NMES protocols and better understand its full benefits in preventing ICU-AW and improving patient outcomes.

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.

The Immediate Analgesic Effect and Impact on Gait Function of Transcutaneous Electrical Nerve Stimulation in Late-Stage Elderly Individuals with Knee Pain: Examination of Gait Function Using an IoT-Based Gait Analysis Device

Purpose: This study verified the effects of transcutaneous electrical nerve stimulation (TENS), which can be worn during walking and exercise, in elderly individuals with late-stage knee pain who exercise regularly. Methods: Thirty-two late-stage elderly individuals were evaluated for knee pain during rest, walking, and program exercises, with and without TENS. Gait analysis was performed using an IoT-based gait analysis device to examine the effects of TENS-induced analgesia on gait. Results: TENS significantly reduced knee pain during rest, walking, and programmed exercises, with the greatest analgesic effect observed during walking. The greater the knee pain without TENS, the more significant the analgesic effect of TENS. A comparison of gait parameters revealed a significant difference only in the gait cycle time, with a trend towards faster walking with TENS;however, the effect was limited. Conclusion: TENS effectively relieves knee pain in late-stage elderly individuals and can be safely applied during exercise. Pain management using TENS provides important insights into the implementation of exercise therapy in this age group.

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.

Analysis of the Effect of Transcutaneous Electrical Stimulation of Acupoints Combined with Rehabilitation Training in The Treatment of Upper Limb Dysfunction After Stroke

Objective:To analyze the effect of combining transcutaneous electrical acupoint stimulation(TEAS)with rehabilitation training in patients with upper limb dysfunction after stroke(ULDAS).Methods:A total of 130 ULDAS patients who were hospitalized and rehabilitated in Wuxi Xinwu District Rehabilitation Hospital from May 2021 to May 2023 were selected and randomly divided into Group A(65 cases,rehabilitation training)and Group B(65 cases,rehabilitation training+TEAS).The effects of the two groups were compared.Results:After treatment,the upper limb functional indexes of Group B were better than those of Group A(P<0.05).The rate of muscle tone grades 0-4 in Group B was higher than those of Group A(P<0.05).Conclusion:The function of upper limbs and muscle strength of ULDAS patients improved by combining TEAS with rehabilitation training.

Evaluating the Impact of Transcutaneous Electrical Nerve Stimulation on Patients Undergoing Inguinal Hernia Surgery: A Meta- Analysis of Randomized Controlled Trials

Objective:A comprehensive meta-analysis based on the latest randomized controlled trials(RCTs)was conducted to investigate the effects of transcutaneous electrical nerve stimulation(TENS)on patients undergoing treatment after inguinal hernia surgery.Methods:A detailed search of Embase,PubMed,Web of Science,and the Cochrane Library was performed for RCTs investigating the use of TENS during inguinal hernia surgery up to September 28,2021.The Cochrane tool was applied to assess the risk of bias in the included studies.Results:Seven eligible RCTs with a total of 379 cases were included.The meta-analysis showed a mean difference(MD)in VAS of-1.61[95%CI:-2.20-1.02,P<0.00001]at 2 hours post-operation,VAS MD=-1.33 at 4 hours post-operation[95%CI:-2.84-0.18,P=0.09],VAS MD=-2.36 at 8 hours post-operation[95%CI:-4.04-0.69,P=0.006],and VAS MD=-1.75 at 24 hours post-operation[95%CI:-2.64-0.85,P=0.0001].The cortisol level MD at 24 hours post-operation was-52.56[95%CI:-168.8-63.76,P=0.38].Conclusion:TENS significantly reduces postoperative pain following inguinal hernia surgery and promotes patient recovery.TENS is recommended for patients undergoing inguinal hernia surgery.However,further high-quality studies are needed to confirm additional effects.

Low-Power CMOS IC for Function Electrical Stimulation of Nerves

A low-power IC for function electrical stimulation （FES） of nerves is designed for an implantable system and fabricated in CSMC＇s 0.6μm CMOS technology. The IC can be used for stimulating animals＇ spinal nerve bundles and other nerves connected with a cuff type electrode. It consists of a pre-amplifier,a main amplifier,and an output stage. According to the neural signal spectrum,the bandwidth of the FES signal generator circuit is defined from 1Hz to 400kHz. The gain of the circuit is about 66dB with an output impedance of 900. The 1C can function under a single supply voltage of 3-5V. A rail-to-rail output stage helps to use the coupled power efficiently. The measured time domain performance shows that the bandwidth and the gain of the IC agree with the design. The power consumption is lower than 6mW.

Combinatorial therapies for spinal cord injury repair

Spinal cord injuries have profound detrimental effects on individuals, regardless of whether they are caused by trauma or non-traumatic events. The compromised regeneration of the spinal cord is primarily attributed to damaged neurons, inhibitory molecules, dysfunctional immune response, and glial scarring. Unfortunately, currently, there are no effective treatments available that can fully repair the spinal cord and improve functional outcomes. Nevertheless, numerous pre-clinical approaches have been studied for spinal cord injury recovery, including using biomaterials, cells, drugs, or technological-based strategies. Combinatorial treatments, which target various aspects of spinal cord injury pathophysiology, have been extensively tested in the last decade. These approaches aim to synergistically enhance repair processes by addressing various obstacles faced during spinal cord regeneration. Thus, this review intends to provide scientists and clinicians with an overview of pre-clinical combinatorial approaches that have been developed toward the solution of spinal cord regeneration as well as update the current knowledge about spinal cord injury pathophysiology with an emphasis on the current clinical management.

Passive activity enhances residual control ability in patients with complete spinal cord injury

Patients with complete spinal cord injury retain the potential for volitional muscle activity in muscles located below the spinal injury level.However,because of prolonged inactivity,initial attempts to activate these muscles may not effectively engage any of the remaining neurons in the descending pathway.A previous study unexpectedly found that a brief clinical round of passive activity significantly increased volitional muscle activation,as measured by surface electromyography.In this study,we further explored the effect of passive activity on surface electromyographic signals during volitional control tasks among individuals with complete spinal cord injury.Eleven patients with chronic complete thoracic spinal cord injury were recruited.Surface electromyography data from eight major leg muscles were acquired and compared before and after the passive activity protocol.The results indicated that the passive activity led to an increased number of activated volitional muscles and an increased frequency of activation.Although the cumulative root mean square of surface electromyography amplitude for volitional control of movement showed a slight increase after passive activity,the difference was not statistically significant.These findings suggest that brief passive activity may enhance the ability to initiate volitional muscle activity during surface electromyography tasks and underscore the potential of passive activity for improving residual motor control among patients with motor complete spinal cord 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.

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.

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.

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.

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.

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.

The effects of androgen on penile reflex, erectile response to electrical stimulation and penile NOS activity in the rat

Aim: To investigate the effects of androgen on penile erection through the reflex arc and penile corpus cavernosum,and study the respective roles of testosterone (T) and dihydrotestosterone (DHT) in penile erection in rats. Methods:Male Sprague-Dawley rats were castrated and implanted with silastic brand silicone tube containing T or DHT, with orwithout daily injections of a 5α-reductase inhibitor, MK-434. The penile reflex, erectile response to electrical stimula-tion (ES) of the cavernous nerves and penile nitric-oxide synthase (NOS) activity were observed under varying andro-genic status. Results: Penile reflex erection in the rat was, on the whole, related to serum T levels though the numberof glans engorgements was not. The number of cups and flips was significantly decreased by castration, and restoredto the control level by T supplementation. Erectile response to ES and NOS activity in penile tissue was also related toserum T level. T administered together with a 5α-reductase inhibitor no longer restored the number of reflex erection,erectile responses to ES and NOS activity in the corpus cavernosum. Conclusion: Androgen influenced the penile re-flex arc, corpus cavernosum, and the perineal striated muscles. In reflex erection, erectile response to ES and penileNOS activity in the rat, T seems to be first converted to DHT, the more active androgen modality. (Asian J Androl1999 Dec; 1: 169-174)

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.