Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of kn...Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.展开更多
Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance to...Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance tomography enables real-time monitoring of changes in cerebral blood perfusion within the ischemic brain,but investigating the feasibility of using this method to assess post-stroke rehabilitation in vivo remains critical.In this study,ischemic stroke was induced in rats through middle cerebral artery occlusion surgery.Transcranial focused ultrasound stimulation was used to treat the rat model of ischemia,and electrical impedance tomography was used to measure impedance during both the acute stage of ischemia and the rehabilitation stage following the stimulation.Electrical impedance tomography results indicated that cerebral impedance increased after the onset of ischemia and decreased following transcranial focused ultrasound stimulation.Furthermore,the stimulation promoted motor function recovery,reduced cerebral infarction volume in the rat model of ischemic stroke,and induced the expression of brain-derived neurotrophic factor in the ischemic brain.Our results also revealed a significant correlation between the impedance of the ischemic brain post-intervention and improvements in behavioral scores and infarct volume.This study shows that daily administration of transcranial focused ultrasound stimulation for 20 minutes to the ischemic hemisphere 24 hours after cerebral ischemia enhanced motor recovery in a rat model of ischemia.Additionally,our findings indicate that electrical impedance tomography can serve as a valuable tool for quantitatively evaluating rehabilitation after ischemic stroke in vivo.These findings suggest the feasibility of using impedance data collected via electrical impedance tomography to clinically assess the effects of rehabilitatory interventions for patients with ischemic stroke.展开更多
The continuous extension of human life expectancy and the global trend of population aging have contributed to a marked increase in the incidence of musculoskeletal diseases,with fractures and osteoporosis being promi...The continuous extension of human life expectancy and the global trend of population aging have contributed to a marked increase in the incidence of musculoskeletal diseases,with fractures and osteoporosis being prominent examples.Consequently,promoting bone regeneration is a crucial medical challenge that demands immediate attention.As early as the mid-20th century,researchers revealed that electrical stimulation could effectively promote the healing and regeneration of bone tissue.This is achieved by mimicking the endogenous electric field within bone tissue,which influences cellular behavior and molecular mechanisms.In recent years,electroactive hydrogels responsive to electric field stimulation have been developed and applied to regulate cell functions at different stages of bone regeneration.This paper elaborates on the regulatory effects of electrical stimulation on MSCs,macrophages,and vascular endothelial cells during the process of bone regeneration.It also involves the activation of relevant ion channels and signaling pathways.Subsequently,it comprehensively reviews various electric-field-responsive hydrogels developed in recent years,covering aspects such as material selection,preparation methods,characteristics,and their applications in bone regeneration.Ultimately,it provides an objective summary of the existing deficiencies in hydrogel materials and research,and looks ahead to future development directions.展开更多
Chronic pain following a spinal cord injury refers to pain that persists or recurs after the injury.This pain can manifest as burning,stinging,or sensations similar to electric shocks.Recent studies have shown that sp...Chronic pain following a spinal cord injury refers to pain that persists or recurs after the injury.This pain can manifest as burning,stinging,or sensations similar to electric shocks.Recent studies have shown that spinal cord stimulation is an effective way to treat chronic pain after spinal cord injury.The purpose of this review is to introduce the technique of spinal cord stimulation,the clinical manifestations of spinal cord injury,and the role of spinal cord stimulation in the treatment of spinal cord injury.The mechanism and clinical application of spinal cord stimulation in the treatment of pain after spinal cord injury are discussed.The mechanism of spinal cord stimulation primarily involves three aspects:neuromodulation,neurochemical regulation,and anti-inflammatory effects,along with nerve repair.In terms of neuromodulation,spinal cord stimulation is based on the gate control theory of pain.It activates large-diameter amyloid-βnerve fibers to promote the release of inhibitory neurotransmitters by gamma-aminobutyric acidergic inhibitory interneurons in the spinal cord,thereby blocking the transmission of pain signals from small-diameter C fibers.Neurochemical studies indicate that spinal cord stimulation can regulate the balance of neurotransmitters within the spinal cord,increasing the release of inhibitory neurotransmitters such as gamma-aminobutyric acid,serotonin,and acetylcholine while reducing the levels of excitatory neurotransmitters.Additionally,spinal cord stimulation exhibits significant anti-inflammatory and neuroprotective effects,downregulating pro-inflammatory factor levels,upregulating anti-inflammatory factor expression,alleviating neuroinflammatory responses,and repairing damaged neural circuits by promoting the secretion of neurotrophic factors and axonal regeneration.Spinal cord stimulation have demonstrated remarkable efficacy in the clinical treatment of pain after spinal cord injury,but there are still limitations such as small sample size and high heterogeneity in clinical studies,as well as insufficient long-term efficacy data.Future research should conduct multi-center large-sample randomized controlled trials,and establish long-term follow-up mechanisms to improve evidence-based medical evidence.展开更多
Neuromuscular electrical stimulation(NMES)is a well-established therapeutic approach for chronic wounds.Conventionally,NMES involves direct electrode contact with wounds or adjacent healthy skin;however,it is limited ...Neuromuscular electrical stimulation(NMES)is a well-established therapeutic approach for chronic wounds.Conventionally,NMES involves direct electrode contact with wounds or adjacent healthy skin;however,it is limited by the need for wound exposure and by increased pain.Our preliminary study demonstrated the innovative application of remote NMES(rNMES)to the skeletal muscle of the distal calf,which showed the potential to accelerate wound healing in remote areas.rNMES was effective in human clinical trials in our previous work,although the underlying mechanisms remain unclear.As rNMES is often used to stimulate muscle contraction in long-term bedridden patients,we analyzed data from the Gene Expression Omnibus(GEO)database and found that exercise promotes midkine(MDK)expression in muscle.MDK is a small secreted heparin-binding protein that interacts with multiple cell surface receptors to promote growth.In the present study,we found that MDK significantly enhanced macrophage efferocytosis in a low-density lipoprotein receptor-related protein 1(LRP1)-dependent manner.Our findings demonstrate that rNMES upregulates MDK expression in skeletal muscles through the AMPK-ERK axis,facilitating its delivery to wounds through the circulatory system and promoting LRP1-mediated efferocytosis of apoptotic cells,thereby expediting wound healing.展开更多
Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize...Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize electrical stimulation to directly or indirectly target specific brain regions,modulating neural activity and influencing broader brain networks,thereby regulating cognitive function.Regulating cognitive function involves an understanding of aspects such as perception,learning and memory,attention,spatial cognition,and physical function.To enhance the application of cognitive regulation in the general population,this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions.This review covers various neuromodulation techniques for cognitive intervention,including deep brain stimulation,vagus nerve stimulation,and invasive methods using microelectrode arrays.The non-invasive techniques discussed include transcranial magnetic stimulation,transcranial direct current stimulation,transcranial alternating current stimulation,transcutaneous electrical acupoint stimulation,and time interference stimulation for activating deep targets.Invasive stimulation methods,which are ideal for studying the pathogenesis of neurological diseases,tend to cause greater trauma and have been less researched in the context of cognitive function regulation.Non-invasive methods,particularly newer transcranial stimulation techniques,are gentler and more appropriate for regulating cognitive functions in the general population.These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets.This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology.It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation.Additionally,researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.展开更多
Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despit...Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despite differences in the mechanisms of injury,both conditions share a high prevalence of motor and cognitive impairments.These deficits show only limited natural recovery.展开更多
Alzheimer's disease is the most common type of cognitive disorder,and there is an urgent need to develop more effective,targeted and safer therapies for patients with this condition.Deep brain stimulation is an in...Alzheimer's disease is the most common type of cognitive disorder,and there is an urgent need to develop more effective,targeted and safer therapies for patients with this condition.Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation.As an emerging therapeutic approach,deep brain stimulation shows significant promise as a potential new therapy for Alzheimer's disease.Here,we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer's disease based on existing clinical and basic research.In clinical studies,the most commonly targeted sites include the fornix,the nucleus basalis of Meynert,and the ventral capsule/ventral striatum.Basic research has found that the most frequently targeted areas include the fornix,nucleus basalis of Meynert,hippocampus,entorhinal cortex,and rostral intralaminar thalamic nucleus.All of these individual targets exhibit therapeutic potential for patients with Alzheimer's disease and associated mechanisms of action have been investigated.Deep brain stimulation may exert therapeutic effects on Alzheimer's disease through various mechanisms,including reducing the deposition of amyloid-β,activation of the cholinergic system,increasing the levels of neurotrophic factors,enhancing synaptic activity and plasticity,promoting neurogenesis,and improving glucose metabolism.Currently,clinical trials investigating deep brain stimulation for Alzheimer's disease remain insufficient.In the future,it is essential to focus on translating preclinical mechanisms into clinical trials.Furthermore,consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer's disease,including cognitive function,neuropsychiatric symptoms,quality of life and changes in Alzheimer's disease biomarkers.Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows,such as the prodromal and even the preclinical stages of Alzheimer's disease.Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer's disease.展开更多
Transcranial direct current stimulation(tDCS)is a non-invasive technique that modifies cortical excitability and induces neuroplasticity using low-intensity electrical currents.Nuclear medicine technologies like posit...Transcranial direct current stimulation(tDCS)is a non-invasive technique that modifies cortical excitability and induces neuroplasticity using low-intensity electrical currents.Nuclear medicine technologies like positron emission tomography(PET)and single-photon emission computed tomography(SPECT)can quantify cerebral metabolism and other dynamics.Evidence suggests that combining tDCS with these imaging methods enhances understanding and outcomes for neurological and psychiatric conditions.This review highlights how nuclear medicine can objectively characterize tDCS eff ects,map network modulation,and identify predictive biomarkers.PET and SPECT indicate changes in glucose metabolism and neurotransmitter activity post-tDCS,demonstrating their value in validation.While the co-application of these methodologies is still in conceptual stages,their integration may advance precision neuromodulation and inform rehabilitation strategies.展开更多
Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established a...Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established an omohyoid muscle-based PNS rat model combined with MV.Bilateral nerves were exposed within 20±2 min by transection at the intermediate tendon of omohyoid muscle,minimizing trauma and bleeding.Threshold stimulation(0.6±0.2 mA)correlated with body weight.Ventilator-synchronized stimulation increased compound muscle action potentials by~30%,whereas histology confirmed intact nerve.Physiological parameters remained stable throughout ventilation.This model provides a safe and scalable platform for mechanistic and preclinical studies on PNS-mediated protection against MV-induced organ injury.展开更多
The neurovascular unit plays a critical role in maintaining brain structure,function,and homeostasis.Following ischemic stroke,dysfunction and dysregulation of this unit contribute to nerve-blood vessel uncoupling.Int...The neurovascular unit plays a critical role in maintaining brain structure,function,and homeostasis.Following ischemic stroke,dysfunction and dysregulation of this unit contribute to nerve-blood vessel uncoupling.Intermittent theta-burst stimulation is a repetitive transcranial magnetic stimulation that operates within the theta wave range and can either promote or inhibit cortical excitability.Previous studies have shown that intermittent theta wave stimulation has neuroprotective effects,but the underlying mechanisms remain unclear.In this study,mice subjected to middle cerebral artery occlusion/reperfusion were treated with intermittent theta-burst stimulation.The results showed that intermittent theta-burst stimulation significantly improved neurological function and motor recovery,reduced apoptosis in the peri-infarct region,and activated the PI3K/AKT/GSK3β/β-catenin signaling pathway.Additionally,intermittent theta-burst stimulation suppressed inflammation through the PI3K/AKT/GSK3βand NF-κB pathways.Notably,intermittent theta-burst stimulation strengthened A2 astrocyte-blood vessel coupling,and the effects of intermittent theta-burst stimulation were reversed by the PI3K inhibitor LY294002.These findings demonstrate that intermittent theta-burst stimulation promotes neurovascular unit remodeling and improves neurological outcomes by modulating microglia and astrocytes via the PI3K/AKT/GSK3βand NF-κB signaling pathways.展开更多
Exercise produces a decrease in pain sensitivity via an effect called exercise-induced hypoalgesia(EIH).Transcranial direct current stimulation(tDCS),acting on similar analgesic mechanisms as EIH,represents a potentia...Exercise produces a decrease in pain sensitivity via an effect called exercise-induced hypoalgesia(EIH).Transcranial direct current stimulation(tDCS),acting on similar analgesic mechanisms as EIH,represents a potential complementary intervention that may amplify the effects of exercise on pain.This study aimed to explore if anodal tDCS could enhance the effect of exercise on pain compared to exercise alone.A total of 35 healthy participants aged 19–37 years completed a familiarisation session followed by two separate sessions where active and sham tDCS was applied in a randomised cross-over design.The familiarisation session involved familiarisation to the pain assessment and exercise tasks,while the subsequent tDCS sessions involved pain sensitivity assessment,exercise and either anodal tDCS or sham tDCS.tDCS doses were applied at 2 mA over the primary motor cortex for 10 min,with the reference electrode placed over the contralateral supraorbital area.The exercise task involved a sustained isometric grip strength contraction at 35%of maximal voluntary contraction(MVC)until volitional exhaustion.Pain sensitivity was evaluated as pressure pain threshold before tDCS,after tDCS,and after exercise.Across both tDCS conditions,pain threshold was higher after exercise when compared to pre-and post-tDCS measurement.This increase in pain threshold did not differ between active and sham tDCS conditions.Our findings suggest that the hypoalgesic effects of active anodal tDCS over the motor cortex prior to exercise are no greater than the effects of sham tDCS prior to exercise.展开更多
Disorders of consciousness(DoC),including coma,vegetative state,and minimally conscious state,present a spectrum of conditions characterized by impaired awareness and responsiveness due to severe brain injury.Conventi...Disorders of consciousness(DoC),including coma,vegetative state,and minimally conscious state,present a spectrum of conditions characterized by impaired awareness and responsiveness due to severe brain injury.Conventional interventions for DoC primarily focus on promoting conditions conducive to spontaneous neurological recovery including pharmacological treatments such as dopaminergic agents(e.g.,amantadine)and rehabilitative strategies including sensory stimulation programs and physical therapy.展开更多
Current pharmacotherapy for neurodegenerative diseases is limited to providing symptomatic relief,instead of slowing or reversing disease progression.As a form of neuromodulation surgery,deep brain stimulation deliver...Current pharmacotherapy for neurodegenerative diseases is limited to providing symptomatic relief,instead of slowing or reversing disease progression.As a form of neuromodulation surgery,deep brain stimulation delivers electrical pulses thro ugh implanted electrodes in targeted brain regions and has been used to alleviate symptoms in neurodegenerative diseases.Depending on the precise targeting of neural modulation,deep brain stimulation is being explo red for its potential to manage symptoms and improve overall quality of life in neurodegenerative diseases associated with cognitive impairment,such as Alzheimer's disease and dementia in Parkinson's disease.The nucleus basalis of Meynert,a critical component of the cerebral cholinergic system and the Papez circuit,is considered as a promising target for treating cognitive dysfunction in neurodegenerative diseases due to its essential role in regulating cognition,memory,and attention.However,the comprehensive mechanisms by which deep brain stimulation of nucleus basalis of Meynert affects neurodegenerative diseases with cognitive impairment remain largely unchara cterized.Nonetheless,various hypotheses and evidence from animal and clinical studies suggest mechanisms such as the modeulation of the choline rgic system,increased glucose metabolism and regional cerebral blood flow,neuroprotective effects,and the modulation of neural networks.In this review,we update the advances in research rega rding the therapeutic effects and potential mechanisms of deep brain stimulation of nucleus basalis of Meynert on cognitive impairment in neurodegenerative diseases.Additionally,we examine the anatomy,connectivity,and physiological functions of the nucleus basalis of M eynert.Deep brain stimulation of nucleus basalis of Meynert may improve cognitive impairment in neurodegenerative diseases through multiple mechanisms;howeve r,further larger-scale,multi-center clinical trials conducted at earlier disease stages are necessary to fully confirm its efficacy and safety.展开更多
Tactile feedback is critical for human interaction with external information.Similarly,tactile feedback can enrich the user's sensations when using prosthesis.To explore a potential scheme for tactile feedback,thi...Tactile feedback is critical for human interaction with external information.Similarly,tactile feedback can enrich the user's sensations when using prosthesis.To explore a potential scheme for tactile feedback,this study applied a non-inva-sive Transcutaneous Electrical Nerve Stimulation(TENS)to elicit tactile sensations in the hand,which involved median nerve,ulnar nerve,and radial nerve.Ten able-bodied subjects(8 males,2 females)were recruited to participate in the study.An array of 4×2 electrodes was positioned on the medial aspect of the brachii muscle's short head in the upper arm,which is in proximity to the median nerve,ulnar nerve,and radial nerve.Different electrode pairs were randomly selected to elicit distinct sensations at various positions on the hand,and the subjects reported the sensory areas.Then,the sensory areas and sensory thresholds were confirmed through psychophysical methods.According to the experimental results,tactile sensations were elicited at different locations on the subjects'hand through TENS of different electrode pairs.All subjects reported extensive and detailed sensory areas in the fingers,palm,and dorsum,corresponding to the sensory innervation areas of different nerves.The study effectively demonstrated the ability of TENS in evoking tactile feedback in the hand,paving the way for future optimization and development of prosthetic hands.展开更多
Background:Hormonal treatment and response as a predictor of sperm retrieval prior to microdissection testicular sperm extraction(micro-TESE)are not well established in the current literature.This study aimed to inves...Background:Hormonal treatment and response as a predictor of sperm retrieval prior to microdissection testicular sperm extraction(micro-TESE)are not well established in the current literature.This study aimed to investigate the hormonal response as a predictor of sperm retrieval among men with nonobstructive azoospermia(NOA).Methods:Seventy-seven consecutive patients who had testosterone levels≤14 nmol/L were treated medically with an aromatase inhibitor or recombinant human chorionic gonadotropin(rec-hCG)prior to micro-TESE and were included.Thirty-four(44.2%)had unexplained NOA(UNEX),25(32.5%)had Klinefelter syndrome(KS),8(10.4%)had a history of cryptorchidism(UDT),4(5.2%)had microdeletion of the Azoospermia factor C(AZFc),and 6(7.8%)were treated previously with chemotherapy.Baseline and post-treatment serum hormonal levels were documented.Pre-op testosterone levels were entered into binary logistic regressions with age,Follicle-stimulating hormone(FSH),and Luteinizing hormone(LH)levels to test for significance with sperm retrieval.We then built logistic regression models to identify predictors of successful surgical sperm retrieval(SSR).Results:Forty-five patients(58%)had successful retrieval.In 32 patients(42%),no sperm was retrieved.Both the mean pre-op testosterone and the mean testosterone change between the two groups were significant(p=0.02 and p=0.011,respectively).Receiver operating characteristic(ROC)analysis demonstrated an area under the curve(AUC)of 0.785(95%CI=0.685-0.886,p<0.001).The Youden index coefficient was calculated for KS and UNEX.The cut-off point for KS was established at 0.764(sensitivity=0.875,false positive rate[FPR]=0.111),and 0.215 for UNEX(sensitivity=0.438,FPR=0.222).We also observed a correlation between age and SSR(p=0.05).In KS patients,SSR was determined by pre-op testosterone levels irrespective of age.Conclusion:Pre-operative hormonal response is a predictor for SSR in NOA patients who were treated medically.This data may help during pre-operative counselling.展开更多
Current treatments for neuropathic pain are suboptimal,necessitating the search for more effective therapeutics.Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effec...Current treatments for neuropathic pain are suboptimal,necessitating the search for more effective therapeutics.Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effects,and focal repetitive trans-spinal magnetic stimulation showed an anti-neuroinflammatory effect in spinal cord injury rat models.Here,we speculated that repetitive trans-spinal magnetic stimulation might induce an anti-inflammatory effect to alleviate neuropathic pain by upregulating calmodulin-dependent protein kinase kinase beta(CaMKKβ)/adenosine 5′-monophosphate-activated protein kinase(AMPK)/suppressor of cytokine signaling-3(SOCS3)signaling in microglia.Experiments have found that non-invasive focal repetitive trans-spinal magnetic stimulation effectively alleviates mechanical allodynia and spinal neuroinflammation in rats with neuropathic pain induced by chronic sciatic nerve ligation.Further research found that repetitive trans-spinal magnetic stimulation upregulated the expression of SOCS3 in spinal microglia,which subsequently inhibited the phosphorylation of p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 nuclear translocation in rats with neuropathic pain,thereby suppressing neuroinflammation.The upregulation of SOCS3 by repetitive trans-spinal magnetic stimulation may be achieved through the activation of the CaMKKβ/AMPK signaling pathway in microglia.The results suggested that focal repetitive trans-spinal magnetic stimulation inhibits spinal neuroinflammation and alleviates neuropathic pain by activating the CaMKKβ/AMPK/SOCS3 signaling pathway in spinal microglia.This mechanism provides an effective noninvasive treatment for neuropathic pain caused by peripheral nerve injury.展开更多
BACKGROUND Depression has become a global public health problem.In recent years,transcranial magnetic stimulation(TMS)has gained considerable attention as a noninvasive treatment for depression.AIM To investigate the ...BACKGROUND Depression has become a global public health problem.In recent years,transcranial magnetic stimulation(TMS)has gained considerable attention as a noninvasive treatment for depression.AIM To investigate the research hotspots and trends in the field of TMS-based depression treatment from a bibliometric perspective.METHODS Using the Web of Science Core Collection,articles published between 2003 and 2022 on TMS-based depression treatment were retrieved from the science citation index expanded.The publication trends and research hotspots were analyzed using VOSviewer,CiteSpace,and the bibliometric online analysis platform.Regression analysis was performed using Microsoft Excel 2021 to predict publication growth trends.RESULTS We identified a total of 702 articles on TMS-based depression treatment with a predominance of clinical studies.Analysis of collaborative networks showed that the United States,the University of Toronto,and Daskalakis ZJ were identified as the most impactful country,institution,and researcher,respectively.In keyword burst analysis,it was found that theta burst stimulation(TBS),functional connectivity,and frequency were the most recent research hotspots.CONCLUSION TMS provides a novel therapeutic option for patients with treatment-resistant depression.Neuroimaging technology enables more precise TMS treatment,while the novel TMS modality,TBS,enhances both therapeutic efficacy and patient experience in TMS-based depression treatment.The integration of neuroimaging techniques with TBS represents a promising research direction for advancing TMS-based depression treatment.This study presents systematic information and recommendations to guide future research on TMS-based depression treatment.展开更多
A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigati...A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.展开更多
AIM: To evaluate the current state-of-the-art of gastric electrical stimulation to treat obesity. METHODS: Systematic reviews of all studies have been conducted to evaluate the effect of different types of gastric ele...AIM: To evaluate the current state-of-the-art of gastric electrical stimulation to treat obesity. METHODS: Systematic reviews of all studies have been conducted to evaluate the effect of different types of gastric electrical stimulation(GES) on obesity.RESULTS: Thirty-one studies consisting of a total of 33 different trials were included in the systematic review for data analysis. Weight loss was achieved in most studies, especially during the first 12 mo, but only very few studies had a follow-up period longer than 1 year. Among those that had a longer follow-up period, many were from the Transcend(Implantable Gastric Stimulation) device group and maintained significant weight loss. Other significant results included changes in appetite/satiety, gastric emptying rate, blood pressure and neurohormone levels or biochemical markers such as ghrelin or HbA1 c respectively. CONCLUSION: GES holds great promises to be an effective obesity treatment. However, stronger evidence is required through more studies with a standardized way of carrying out trials and reporting outcomes, to determine the long-term effect of GES on obesity.展开更多
基金funded by the Deutsche Forschungsgemeinschaft(DFG,German Research Foundation):project ID 431549029-SFB 1451the Marga-und-Walter-Boll-Stiftung(#210-10-15)(to MAR)a stipend from the'Gerok Program'(Faculty of Medicine,University of Cologne,Germany)。
文摘Noninvasive brain stimulation techniques offer promising therapeutic and regenerative prospects in neurological diseases by modulating brain activity and improving cognitive and motor functions.Given the paucity of knowledge about the underlying modes of action and optimal treatment modalities,a thorough translational investigation of noninvasive brain stimulation in preclinical animal models is urgently needed.Thus,we reviewed the current literature on the mechanistic underpinnings of noninvasive brain stimulation in models of central nervous system impairment,with a particular emphasis on traumatic brain injury and stroke.Due to the lack of translational models in most noninvasive brain stimulation techniques proposed,we found this review to the most relevant techniques used in humans,i.e.,transcranial magnetic stimulation and transcranial direct current stimulation.We searched the literature in Pub Med,encompassing the MEDLINE and PMC databases,for studies published between January 1,2020 and September 30,2024.Thirty-five studies were eligible.Transcranial magnetic stimulation and transcranial direct current stimulation demonstrated distinct strengths in augmenting rehabilitation post-stroke and traumatic brain injury,with emerging mechanistic evidence.Overall,we identified neuronal,inflammatory,microvascular,and apoptotic pathways highlighted in the literature.This review also highlights a lack of translational surrogate parameters to bridge the gap between preclinical findings and their clinical translation.
基金supported by the Fundamental Research Funds for the Central Universities,Nos.G2021KY05107,G2021KY05101the National Natural Science Foundation of China,Nos.32071316,32211530049+1 种基金the Natural Science Foundation of Shaanxi Province,No.2022-JM482the Education and Teaching Reform Funds for the Central Universities,No.23GZ230102(all to LL and HH).
文摘Although previous studies have demonstrated that transcranial focused ultrasound stimulation protects the ischemic brain,clear criteria for the stimulation time window and intensity are lacking.Electrical impedance tomography enables real-time monitoring of changes in cerebral blood perfusion within the ischemic brain,but investigating the feasibility of using this method to assess post-stroke rehabilitation in vivo remains critical.In this study,ischemic stroke was induced in rats through middle cerebral artery occlusion surgery.Transcranial focused ultrasound stimulation was used to treat the rat model of ischemia,and electrical impedance tomography was used to measure impedance during both the acute stage of ischemia and the rehabilitation stage following the stimulation.Electrical impedance tomography results indicated that cerebral impedance increased after the onset of ischemia and decreased following transcranial focused ultrasound stimulation.Furthermore,the stimulation promoted motor function recovery,reduced cerebral infarction volume in the rat model of ischemic stroke,and induced the expression of brain-derived neurotrophic factor in the ischemic brain.Our results also revealed a significant correlation between the impedance of the ischemic brain post-intervention and improvements in behavioral scores and infarct volume.This study shows that daily administration of transcranial focused ultrasound stimulation for 20 minutes to the ischemic hemisphere 24 hours after cerebral ischemia enhanced motor recovery in a rat model of ischemia.Additionally,our findings indicate that electrical impedance tomography can serve as a valuable tool for quantitatively evaluating rehabilitation after ischemic stroke in vivo.These findings suggest the feasibility of using impedance data collected via electrical impedance tomography to clinically assess the effects of rehabilitatory interventions for patients with ischemic stroke.
基金supported by the National Science Foundation of China(No.82272491)。
文摘The continuous extension of human life expectancy and the global trend of population aging have contributed to a marked increase in the incidence of musculoskeletal diseases,with fractures and osteoporosis being prominent examples.Consequently,promoting bone regeneration is a crucial medical challenge that demands immediate attention.As early as the mid-20th century,researchers revealed that electrical stimulation could effectively promote the healing and regeneration of bone tissue.This is achieved by mimicking the endogenous electric field within bone tissue,which influences cellular behavior and molecular mechanisms.In recent years,electroactive hydrogels responsive to electric field stimulation have been developed and applied to regulate cell functions at different stages of bone regeneration.This paper elaborates on the regulatory effects of electrical stimulation on MSCs,macrophages,and vascular endothelial cells during the process of bone regeneration.It also involves the activation of relevant ion channels and signaling pathways.Subsequently,it comprehensively reviews various electric-field-responsive hydrogels developed in recent years,covering aspects such as material selection,preparation methods,characteristics,and their applications in bone regeneration.Ultimately,it provides an objective summary of the existing deficiencies in hydrogel materials and research,and looks ahead to future development directions.
基金supported by Key Tackling Project of the Education Department of Liaoning Province,No.2024C011the Medical-Industrial Joint Innovation Funding Project of the First Hospital of Dalian Medical University and Dalian Institute of Chemical Physics,No.DMU-1&DICP UN202311(both to ZL).
文摘Chronic pain following a spinal cord injury refers to pain that persists or recurs after the injury.This pain can manifest as burning,stinging,or sensations similar to electric shocks.Recent studies have shown that spinal cord stimulation is an effective way to treat chronic pain after spinal cord injury.The purpose of this review is to introduce the technique of spinal cord stimulation,the clinical manifestations of spinal cord injury,and the role of spinal cord stimulation in the treatment of spinal cord injury.The mechanism and clinical application of spinal cord stimulation in the treatment of pain after spinal cord injury are discussed.The mechanism of spinal cord stimulation primarily involves three aspects:neuromodulation,neurochemical regulation,and anti-inflammatory effects,along with nerve repair.In terms of neuromodulation,spinal cord stimulation is based on the gate control theory of pain.It activates large-diameter amyloid-βnerve fibers to promote the release of inhibitory neurotransmitters by gamma-aminobutyric acidergic inhibitory interneurons in the spinal cord,thereby blocking the transmission of pain signals from small-diameter C fibers.Neurochemical studies indicate that spinal cord stimulation can regulate the balance of neurotransmitters within the spinal cord,increasing the release of inhibitory neurotransmitters such as gamma-aminobutyric acid,serotonin,and acetylcholine while reducing the levels of excitatory neurotransmitters.Additionally,spinal cord stimulation exhibits significant anti-inflammatory and neuroprotective effects,downregulating pro-inflammatory factor levels,upregulating anti-inflammatory factor expression,alleviating neuroinflammatory responses,and repairing damaged neural circuits by promoting the secretion of neurotrophic factors and axonal regeneration.Spinal cord stimulation have demonstrated remarkable efficacy in the clinical treatment of pain after spinal cord injury,but there are still limitations such as small sample size and high heterogeneity in clinical studies,as well as insufficient long-term efficacy data.Future research should conduct multi-center large-sample randomized controlled trials,and establish long-term follow-up mechanisms to improve evidence-based medical evidence.
基金supported by the National Natural Science Foundation of China(Grant No.82271252 to W.L.,No.8217091029 to T.W.and No.82204542 to L.H.)the Key Medical Research Projects of Jiangsu Health and Health Commission(Grant No.K2023066 to L.Z.)the Taishan Industrial Talent Project(Grant No.2020-371722-73-03-097290 to W.L.).
文摘Neuromuscular electrical stimulation(NMES)is a well-established therapeutic approach for chronic wounds.Conventionally,NMES involves direct electrode contact with wounds or adjacent healthy skin;however,it is limited by the need for wound exposure and by increased pain.Our preliminary study demonstrated the innovative application of remote NMES(rNMES)to the skeletal muscle of the distal calf,which showed the potential to accelerate wound healing in remote areas.rNMES was effective in human clinical trials in our previous work,although the underlying mechanisms remain unclear.As rNMES is often used to stimulate muscle contraction in long-term bedridden patients,we analyzed data from the Gene Expression Omnibus(GEO)database and found that exercise promotes midkine(MDK)expression in muscle.MDK is a small secreted heparin-binding protein that interacts with multiple cell surface receptors to promote growth.In the present study,we found that MDK significantly enhanced macrophage efferocytosis in a low-density lipoprotein receptor-related protein 1(LRP1)-dependent manner.Our findings demonstrate that rNMES upregulates MDK expression in skeletal muscles through the AMPK-ERK axis,facilitating its delivery to wounds through the circulatory system and promoting LRP1-mediated efferocytosis of apoptotic cells,thereby expediting wound healing.
基金supported by STI 2030-Major Projects,No.2021ZD0201603(to JL)the Joint Foundation Program of the Chinese Academy of Sciences,No.8091A170201(to JL)+1 种基金the National Natural Science Foundation of China,Nos.T2293730(to XC),T2293731(to XC),T2293734(to XC),62471291(to YW),62121003(to XC),61960206012(to XC),62333020(to XC),and 62171434(to XC)the National Key Research and Development Program of China,Nos.2022YFC2402501(to XC),2022YFB3205602(to XC).
文摘Neuromodulation techniques effectively intervene in cognitive function,holding considerable scientific and practical value in fields such as aerospace,medicine,life sciences,and brain research.These techniques utilize electrical stimulation to directly or indirectly target specific brain regions,modulating neural activity and influencing broader brain networks,thereby regulating cognitive function.Regulating cognitive function involves an understanding of aspects such as perception,learning and memory,attention,spatial cognition,and physical function.To enhance the application of cognitive regulation in the general population,this paper reviews recent publications from the Web of Science to assess the advancements and challenges of invasive and non-invasive stimulation methods in modulating cognitive functions.This review covers various neuromodulation techniques for cognitive intervention,including deep brain stimulation,vagus nerve stimulation,and invasive methods using microelectrode arrays.The non-invasive techniques discussed include transcranial magnetic stimulation,transcranial direct current stimulation,transcranial alternating current stimulation,transcutaneous electrical acupoint stimulation,and time interference stimulation for activating deep targets.Invasive stimulation methods,which are ideal for studying the pathogenesis of neurological diseases,tend to cause greater trauma and have been less researched in the context of cognitive function regulation.Non-invasive methods,particularly newer transcranial stimulation techniques,are gentler and more appropriate for regulating cognitive functions in the general population.These include transcutaneous acupoint electrical stimulation using acupoints and time interference methods for activating deep targets.This paper also discusses current technical challenges and potential future breakthroughs in neuromodulation technology.It is recommended that neuromodulation techniques be combined with neural detection methods to better assess their effects and improve the accuracy of non-invasive neuromodulation.Additionally,researching closed-loop feedback neuromodulation methods is identified as a promising direction for future development.
基金supported by the Defitech Foundation(Morges,CH)to FCHthe Bertarelli Foundation-Catalyst program(Gstaad,CH)to FCH+2 种基金the Wyss Center for Bio and Neuroengineering the Lighthouse Partnership for AI-guided Neuromodulation to FCHthe Fonds de recherche du Quebec-Sante(FRQS#342969)to CEPthe Neuro X Postdoctoral Fellowship Program to CEP。
文摘Brain lesions,such as those caused by stroke or traumatic brain injury(TBI),frequently result in persistent motor and cognitive impairments that significantly affect the individual patient's quality of life.Despite differences in the mechanisms of injury,both conditions share a high prevalence of motor and cognitive impairments.These deficits show only limited natural recovery.
基金supported by the Capital Fund for Health Improvement and Research,No.2022-2-2048(to WZ)the National Natural Science Foundation of China,No.81970992(to WZ)+3 种基金Capital Clinical Characteristic Application Research,No.Z121107001012161(to WZ)the Natural Science Foundation of Beijing,No.7082032(to WZ)the Key Technology R&D Program of Beijing Municipal Education Commission,No.KZ201610025030(to WZ)Project of Scientific and Technological Development of Traditional Chinese Medicine in Beijing,No.JJ2018-48(to WZ)。
文摘Alzheimer's disease is the most common type of cognitive disorder,and there is an urgent need to develop more effective,targeted and safer therapies for patients with this condition.Deep brain stimulation is an invasive surgical treatment that modulates abnormal neural activity by implanting electrodes into specific brain areas followed by electrical stimulation.As an emerging therapeutic approach,deep brain stimulation shows significant promise as a potential new therapy for Alzheimer's disease.Here,we review the potential mechanisms and therapeutic effects of deep brain stimulation in the treatment of Alzheimer's disease based on existing clinical and basic research.In clinical studies,the most commonly targeted sites include the fornix,the nucleus basalis of Meynert,and the ventral capsule/ventral striatum.Basic research has found that the most frequently targeted areas include the fornix,nucleus basalis of Meynert,hippocampus,entorhinal cortex,and rostral intralaminar thalamic nucleus.All of these individual targets exhibit therapeutic potential for patients with Alzheimer's disease and associated mechanisms of action have been investigated.Deep brain stimulation may exert therapeutic effects on Alzheimer's disease through various mechanisms,including reducing the deposition of amyloid-β,activation of the cholinergic system,increasing the levels of neurotrophic factors,enhancing synaptic activity and plasticity,promoting neurogenesis,and improving glucose metabolism.Currently,clinical trials investigating deep brain stimulation for Alzheimer's disease remain insufficient.In the future,it is essential to focus on translating preclinical mechanisms into clinical trials.Furthermore,consecutive follow-up studies are needed to evaluate the long-term safety and efficacy of deep brain stimulation for Alzheimer's disease,including cognitive function,neuropsychiatric symptoms,quality of life and changes in Alzheimer's disease biomarkers.Researchers must also prioritize the initiation of multi-center clinical trials of deep brain stimulation with large sample sizes and target earlier therapeutic windows,such as the prodromal and even the preclinical stages of Alzheimer's disease.Adopting these approaches will permit the efficient exploration of more effective and safer deep brain stimulation therapies for patients with Alzheimer's disease.
文摘Transcranial direct current stimulation(tDCS)is a non-invasive technique that modifies cortical excitability and induces neuroplasticity using low-intensity electrical currents.Nuclear medicine technologies like positron emission tomography(PET)and single-photon emission computed tomography(SPECT)can quantify cerebral metabolism and other dynamics.Evidence suggests that combining tDCS with these imaging methods enhances understanding and outcomes for neurological and psychiatric conditions.This review highlights how nuclear medicine can objectively characterize tDCS eff ects,map network modulation,and identify predictive biomarkers.PET and SPECT indicate changes in glucose metabolism and neurotransmitter activity post-tDCS,demonstrating their value in validation.While the co-application of these methodologies is still in conceptual stages,their integration may advance precision neuromodulation and inform rehabilitation strategies.
基金Outstanding Young Investigator Program of Capital Medical University,Grant/Award Number:A2308。
文摘Phrenic nerve stimulation(PNS)may preserve diaphragm activation and mitigate multiorgan injury during mechanical ventilation(MV);however,a minimal invasive rat model integrating PNS with MV is lacking.We established an omohyoid muscle-based PNS rat model combined with MV.Bilateral nerves were exposed within 20±2 min by transection at the intermediate tendon of omohyoid muscle,minimizing trauma and bleeding.Threshold stimulation(0.6±0.2 mA)correlated with body weight.Ventilator-synchronized stimulation increased compound muscle action potentials by~30%,whereas histology confirmed intact nerve.Physiological parameters remained stable throughout ventilation.This model provides a safe and scalable platform for mechanistic and preclinical studies on PNS-mediated protection against MV-induced organ injury.
基金supported by the National Key R&D Program of China,Nos.2021ZD0202805(to XX),2019YFA0709504(to XX)the National Natural Science Foundation of China,Nos.82172544(to YW),32471083(to XX),81972140(to JW),82272604(to HX),82102491(to SC)+1 种基金the Brain Science and Brain-Like Research Project of Shanghai Sixth People’s Hospital,No.ynnkxyb202410(to JZ)Shanghai Science and Technology Committee Sailing Program,No.23YF1403800(to LL).
文摘The neurovascular unit plays a critical role in maintaining brain structure,function,and homeostasis.Following ischemic stroke,dysfunction and dysregulation of this unit contribute to nerve-blood vessel uncoupling.Intermittent theta-burst stimulation is a repetitive transcranial magnetic stimulation that operates within the theta wave range and can either promote or inhibit cortical excitability.Previous studies have shown that intermittent theta wave stimulation has neuroprotective effects,but the underlying mechanisms remain unclear.In this study,mice subjected to middle cerebral artery occlusion/reperfusion were treated with intermittent theta-burst stimulation.The results showed that intermittent theta-burst stimulation significantly improved neurological function and motor recovery,reduced apoptosis in the peri-infarct region,and activated the PI3K/AKT/GSK3β/β-catenin signaling pathway.Additionally,intermittent theta-burst stimulation suppressed inflammation through the PI3K/AKT/GSK3βand NF-κB pathways.Notably,intermittent theta-burst stimulation strengthened A2 astrocyte-blood vessel coupling,and the effects of intermittent theta-burst stimulation were reversed by the PI3K inhibitor LY294002.These findings demonstrate that intermittent theta-burst stimulation promotes neurovascular unit remodeling and improves neurological outcomes by modulating microglia and astrocytes via the PI3K/AKT/GSK3βand NF-κB signaling pathways.
文摘Exercise produces a decrease in pain sensitivity via an effect called exercise-induced hypoalgesia(EIH).Transcranial direct current stimulation(tDCS),acting on similar analgesic mechanisms as EIH,represents a potential complementary intervention that may amplify the effects of exercise on pain.This study aimed to explore if anodal tDCS could enhance the effect of exercise on pain compared to exercise alone.A total of 35 healthy participants aged 19–37 years completed a familiarisation session followed by two separate sessions where active and sham tDCS was applied in a randomised cross-over design.The familiarisation session involved familiarisation to the pain assessment and exercise tasks,while the subsequent tDCS sessions involved pain sensitivity assessment,exercise and either anodal tDCS or sham tDCS.tDCS doses were applied at 2 mA over the primary motor cortex for 10 min,with the reference electrode placed over the contralateral supraorbital area.The exercise task involved a sustained isometric grip strength contraction at 35%of maximal voluntary contraction(MVC)until volitional exhaustion.Pain sensitivity was evaluated as pressure pain threshold before tDCS,after tDCS,and after exercise.Across both tDCS conditions,pain threshold was higher after exercise when compared to pre-and post-tDCS measurement.This increase in pain threshold did not differ between active and sham tDCS conditions.Our findings suggest that the hypoalgesic effects of active anodal tDCS over the motor cortex prior to exercise are no greater than the effects of sham tDCS prior to exercise.
文摘Disorders of consciousness(DoC),including coma,vegetative state,and minimally conscious state,present a spectrum of conditions characterized by impaired awareness and responsiveness due to severe brain injury.Conventional interventions for DoC primarily focus on promoting conditions conducive to spontaneous neurological recovery including pharmacological treatments such as dopaminergic agents(e.g.,amantadine)and rehabilitative strategies including sensory stimulation programs and physical therapy.
基金National Key Project of Common and Frequently Occurring Diseases,No.2022YFC25038001the National Natural Science Foundation of China,Nos.82472100,81974279the Natural Science Foundation of Hubei Province,No.2022CFB279(all to HK)。
文摘Current pharmacotherapy for neurodegenerative diseases is limited to providing symptomatic relief,instead of slowing or reversing disease progression.As a form of neuromodulation surgery,deep brain stimulation delivers electrical pulses thro ugh implanted electrodes in targeted brain regions and has been used to alleviate symptoms in neurodegenerative diseases.Depending on the precise targeting of neural modulation,deep brain stimulation is being explo red for its potential to manage symptoms and improve overall quality of life in neurodegenerative diseases associated with cognitive impairment,such as Alzheimer's disease and dementia in Parkinson's disease.The nucleus basalis of Meynert,a critical component of the cerebral cholinergic system and the Papez circuit,is considered as a promising target for treating cognitive dysfunction in neurodegenerative diseases due to its essential role in regulating cognition,memory,and attention.However,the comprehensive mechanisms by which deep brain stimulation of nucleus basalis of Meynert affects neurodegenerative diseases with cognitive impairment remain largely unchara cterized.Nonetheless,various hypotheses and evidence from animal and clinical studies suggest mechanisms such as the modeulation of the choline rgic system,increased glucose metabolism and regional cerebral blood flow,neuroprotective effects,and the modulation of neural networks.In this review,we update the advances in research rega rding the therapeutic effects and potential mechanisms of deep brain stimulation of nucleus basalis of Meynert on cognitive impairment in neurodegenerative diseases.Additionally,we examine the anatomy,connectivity,and physiological functions of the nucleus basalis of M eynert.Deep brain stimulation of nucleus basalis of Meynert may improve cognitive impairment in neurodegenerative diseases through multiple mechanisms;howeve r,further larger-scale,multi-center clinical trials conducted at earlier disease stages are necessary to fully confirm its efficacy and safety.
基金National Natural Science Foundation of China(Grant No.52525504)Emerging Frontiers Cultivation Program of Tianjin University Interdisciplinary Center.
文摘Tactile feedback is critical for human interaction with external information.Similarly,tactile feedback can enrich the user's sensations when using prosthesis.To explore a potential scheme for tactile feedback,this study applied a non-inva-sive Transcutaneous Electrical Nerve Stimulation(TENS)to elicit tactile sensations in the hand,which involved median nerve,ulnar nerve,and radial nerve.Ten able-bodied subjects(8 males,2 females)were recruited to participate in the study.An array of 4×2 electrodes was positioned on the medial aspect of the brachii muscle's short head in the upper arm,which is in proximity to the median nerve,ulnar nerve,and radial nerve.Different electrode pairs were randomly selected to elicit distinct sensations at various positions on the hand,and the subjects reported the sensory areas.Then,the sensory areas and sensory thresholds were confirmed through psychophysical methods.According to the experimental results,tactile sensations were elicited at different locations on the subjects'hand through TENS of different electrode pairs.All subjects reported extensive and detailed sensory areas in the fingers,palm,and dorsum,corresponding to the sensory innervation areas of different nerves.The study effectively demonstrated the ability of TENS in evoking tactile feedback in the hand,paving the way for future optimization and development of prosthetic hands.
文摘Background:Hormonal treatment and response as a predictor of sperm retrieval prior to microdissection testicular sperm extraction(micro-TESE)are not well established in the current literature.This study aimed to investigate the hormonal response as a predictor of sperm retrieval among men with nonobstructive azoospermia(NOA).Methods:Seventy-seven consecutive patients who had testosterone levels≤14 nmol/L were treated medically with an aromatase inhibitor or recombinant human chorionic gonadotropin(rec-hCG)prior to micro-TESE and were included.Thirty-four(44.2%)had unexplained NOA(UNEX),25(32.5%)had Klinefelter syndrome(KS),8(10.4%)had a history of cryptorchidism(UDT),4(5.2%)had microdeletion of the Azoospermia factor C(AZFc),and 6(7.8%)were treated previously with chemotherapy.Baseline and post-treatment serum hormonal levels were documented.Pre-op testosterone levels were entered into binary logistic regressions with age,Follicle-stimulating hormone(FSH),and Luteinizing hormone(LH)levels to test for significance with sperm retrieval.We then built logistic regression models to identify predictors of successful surgical sperm retrieval(SSR).Results:Forty-five patients(58%)had successful retrieval.In 32 patients(42%),no sperm was retrieved.Both the mean pre-op testosterone and the mean testosterone change between the two groups were significant(p=0.02 and p=0.011,respectively).Receiver operating characteristic(ROC)analysis demonstrated an area under the curve(AUC)of 0.785(95%CI=0.685-0.886,p<0.001).The Youden index coefficient was calculated for KS and UNEX.The cut-off point for KS was established at 0.764(sensitivity=0.875,false positive rate[FPR]=0.111),and 0.215 for UNEX(sensitivity=0.438,FPR=0.222).We also observed a correlation between age and SSR(p=0.05).In KS patients,SSR was determined by pre-op testosterone levels irrespective of age.Conclusion:Pre-operative hormonal response is a predictor for SSR in NOA patients who were treated medically.This data may help during pre-operative counselling.
基金National Natural Science Foundation of China,Nos.82302877(to QW),82172541(to TW)the Natural Science Foundation of Hunan Province,No.2023JJ30549(to QW)Clinical Medical Technology Innovation Guidance Project of Hunan Provincial Science and Technology Department,No.2021SK51815(to QW).
文摘Current treatments for neuropathic pain are suboptimal,necessitating the search for more effective therapeutics.Our previous study showed that inhibition of neuroinflammation in the spinal cord induced analgesic effects,and focal repetitive trans-spinal magnetic stimulation showed an anti-neuroinflammatory effect in spinal cord injury rat models.Here,we speculated that repetitive trans-spinal magnetic stimulation might induce an anti-inflammatory effect to alleviate neuropathic pain by upregulating calmodulin-dependent protein kinase kinase beta(CaMKKβ)/adenosine 5′-monophosphate-activated protein kinase(AMPK)/suppressor of cytokine signaling-3(SOCS3)signaling in microglia.Experiments have found that non-invasive focal repetitive trans-spinal magnetic stimulation effectively alleviates mechanical allodynia and spinal neuroinflammation in rats with neuropathic pain induced by chronic sciatic nerve ligation.Further research found that repetitive trans-spinal magnetic stimulation upregulated the expression of SOCS3 in spinal microglia,which subsequently inhibited the phosphorylation of p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3 and nuclear factor-kappa B p65 nuclear translocation in rats with neuropathic pain,thereby suppressing neuroinflammation.The upregulation of SOCS3 by repetitive trans-spinal magnetic stimulation may be achieved through the activation of the CaMKKβ/AMPK signaling pathway in microglia.The results suggested that focal repetitive trans-spinal magnetic stimulation inhibits spinal neuroinflammation and alleviates neuropathic pain by activating the CaMKKβ/AMPK/SOCS3 signaling pathway in spinal microglia.This mechanism provides an effective noninvasive treatment for neuropathic pain caused by peripheral nerve injury.
基金Supported by the National Natural Science Foundation of China,No.82270916,No.81800748 and No.82371478the Third Affiliated Hospital of Anhui Medical University Basic and Clinical Collaborative Research Enhancement Program Cultivation Special Funding Project,No.2022sfy009.
文摘BACKGROUND Depression has become a global public health problem.In recent years,transcranial magnetic stimulation(TMS)has gained considerable attention as a noninvasive treatment for depression.AIM To investigate the research hotspots and trends in the field of TMS-based depression treatment from a bibliometric perspective.METHODS Using the Web of Science Core Collection,articles published between 2003 and 2022 on TMS-based depression treatment were retrieved from the science citation index expanded.The publication trends and research hotspots were analyzed using VOSviewer,CiteSpace,and the bibliometric online analysis platform.Regression analysis was performed using Microsoft Excel 2021 to predict publication growth trends.RESULTS We identified a total of 702 articles on TMS-based depression treatment with a predominance of clinical studies.Analysis of collaborative networks showed that the United States,the University of Toronto,and Daskalakis ZJ were identified as the most impactful country,institution,and researcher,respectively.In keyword burst analysis,it was found that theta burst stimulation(TBS),functional connectivity,and frequency were the most recent research hotspots.CONCLUSION TMS provides a novel therapeutic option for patients with treatment-resistant depression.Neuroimaging technology enables more precise TMS treatment,while the novel TMS modality,TBS,enhances both therapeutic efficacy and patient experience in TMS-based depression treatment.The integration of neuroimaging techniques with TBS represents a promising research direction for advancing TMS-based depression treatment.This study presents systematic information and recommendations to guide future research on TMS-based depression treatment.
基金supported by the National Natural Science Foundation of China,No.82001155(to LL)the Natural Science Foundation of Zhejiang Province,No.LY23H090004(to LL)+5 种基金the Natural Science Foundation of Ningbo,No.2023J068(to LL)the Fundamental Research Funds for the Provincial Universities of Zhejiang Province,No.SJLY2023008(to LL)the College Students'Scientific and Technological Innovation Project(Xin Miao Talent Plan)of Zhejiang Province,No.2022R405A045(to CC)the Student ResearchInnovation Program(SRIP)of Ningbo University,Nos.20235RIP1919(to CZ),2023SRIP1938(to YZ)the K.C.Wong Magna Fund in Ningbo University。
文摘A reduction in adult neurogenesis is associated with behavioral abnormalities in patients with Alzheimer's disease.Consequently,enhancing adult neurogenesis represents a promising therapeutic approach for mitigating disease symptoms and progression.Nonetheless,nonpharmacological interventions aimed at inducing adult neurogenesis are currently limited.Although individual non-pharmacological interventions,such as aerobic exercise,acousto-optic stimulation,and olfactory stimulation,have shown limited capacity to improve neurogenesis and cognitive function in patients with Alzheimer's disease,the therapeutic effect of a strategy that combines these interventions has not been fully explored.In this study,we observed an age-dependent decrease in adult neurogenesis and a concurrent increase in amyloid-beta accumulation in the hippocampus of amyloid precursor protein/presenilin 1 mice aged 2-8 months.Amyloid deposition became evident at 4 months,while neurogenesis declined by 6 months,further deteriorating as the disease progressed.However,following a 4-week multifactor stimulation protocol,which encompassed treadmill running(46 min/d,10 m/min,6 days per week),40 Hz acousto-optic stimulation(1 hour/day,6 days/week),and olfactory stimulation(1 hour/day,6 days/week),we found a significant increase in the number of newborn cells(5'-bromo-2'-deoxyuridine-positive cells),immature neurons(doublecortin-positive cells),newborn immature neurons(5'-bromo-2'-deoxyuridine-positive/doublecortin-positive cells),and newborn astrocytes(5'-bromo-2'-deoxyuridine-positive/glial fibrillary acidic protein-positive cells).Additionally,the amyloid-beta load in the hippocampus decreased.These findings suggest that multifactor stimulation can enhance adult hippocampal neurogenesis and mitigate amyloid-beta neuropathology in amyloid precursor protein/presenilin 1 mice.Furthermore,cognitive abilities were improved,and depressive symptoms were alleviated in amyloid precursor protein/presenilin 1 mice following multifactor stimulation,as evidenced by Morris water maze,novel object recognition,forced swimming test,and tail suspension test results.Notably,the efficacy of multifactor stimulation in consolidating immature neurons persisted for at least 2weeks after treatment cessation.At the molecular level,multifactor stimulation upregulated the expression of neuron-related proteins(NeuN,doublecortin,postsynaptic density protein-95,and synaptophysin),anti-apoptosis-related proteins(Bcl-2 and PARP),and an autophagyassociated protein(LC3B),while decreasing the expression of apoptosis-related proteins(BAX and caspase-9),in the hippocampus of amyloid precursor protein/presenilin 1 mice.These observations might be attributable to both the brain-derived neurotrophic factor-mediated signaling pathway and antioxidant pathways.Furthermore,serum metabolomics analysis indicated that multifactor stimulation regulated differentially expressed metabolites associated with cell apoptosis,oxidative damage,and cognition.Collectively,these findings suggest that multifactor stimulation is a novel non-invasive approach for the prevention and treatment of Alzheimer's disease.
文摘AIM: To evaluate the current state-of-the-art of gastric electrical stimulation to treat obesity. METHODS: Systematic reviews of all studies have been conducted to evaluate the effect of different types of gastric electrical stimulation(GES) on obesity.RESULTS: Thirty-one studies consisting of a total of 33 different trials were included in the systematic review for data analysis. Weight loss was achieved in most studies, especially during the first 12 mo, but only very few studies had a follow-up period longer than 1 year. Among those that had a longer follow-up period, many were from the Transcend(Implantable Gastric Stimulation) device group and maintained significant weight loss. Other significant results included changes in appetite/satiety, gastric emptying rate, blood pressure and neurohormone levels or biochemical markers such as ghrelin or HbA1 c respectively. CONCLUSION: GES holds great promises to be an effective obesity treatment. However, stronger evidence is required through more studies with a standardized way of carrying out trials and reporting outcomes, to determine the long-term effect of GES on obesity.
