Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus.It is one of the major resultants of pharmacoresistance and...Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus.It is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy,but still lacks effective treatments.Here,we aimed to test the effects of low-frequency stimulation(LFS)at the subiculum for secondary epileptogenesis in a mouse model.Here,secondary epileptogenesis was simulated at regions both contralateral and ipsilateral to the primary focus by applying successive kindling stimuli.Mice kindled at the right CA3 showed higher seizure susceptibilities at both the contralateral CA3 and the ipsilateral entorhinal cortex and had accelerated kindling processes compared with naive mice.LFS at the ipsilateral subiculum during the primary kindling progress at the right CA3 effectively prevented secondary epileptogenesis at both the contralateral CA3 and the ipsilateral entorhinal cortex,characterized by decreased seizure susceptibilities and a retarded kindling process at those secondary foci.Only application along with the primary epileptogenesis was effective.Notably,the effects of LFS on secondary epileptogenesis were associated with its inhibitory effect at the secondary focus through interfering with the enhancement of synaptic connections between the primary and secondary foci.These results imply that LFS at the subiculum is an effective preventive strategy for extensive secondary epileptogenesis in temporal lobe epilepsy and present the subiculum as a target with potential translational importance.展开更多
Since the last decade deep brain stimulation has been proposed as an alternative treatment for patients who do not become seizure-free with the current pharmacological treatments and cannot undergo resective surgical ...Since the last decade deep brain stimulation has been proposed as an alternative treatment for patients who do not become seizure-free with the current pharmacological treatments and cannot undergo resective surgical procedure. However, the optimal stimulation parameters remain undetermined and active research in humans and animals is necessary. The present study was designed to investigate the effect of unilateral Low Frequency Stimulation (LFS) of hippocampus on seizure development by using the hippocampal rapid kindling method (hRK) in rats. We used male Wistar rats implanted with electrodes in the ventral hippocampus. All rats underwent hRK (biphasic square wave pulses, 20 Hz for 10 seconds) during three consecutive days (twelve stimulations per day). The control group (hRK;n = 6) received only RK stimulus, while the treated group (LFS-hRK;n = 8) received also LFS (biphasic square wave pulses, 1 Hz for 30 seconds) immediately before the RK stimulus, during three consecutive days. At the end of behavioral testing on day 3, 62% (P < 0.05) of the animals receiving LFS treatment were still not fully kindled staying in stages 0-III (P < 0.01). The number of stimulations needed to achieve generalized seizures (stage IV-V of Racine scale) was significantly higher (P < 0.05) in the LFS group with respect to control group. No significant differences in the cumulative daily afterdischarge duration were observed between both groups. These findings suggest that preemptive LFS can significantly decrease the incidence of hippocampus-kindled seizures and delay the progression and secondary generalization of focal seizures.展开更多
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
AIM:To study the relationships between amplitude of low-frequency fluctuations(ALFF)changes and clinical ophthalmic parameters in patients with primary open angle glaucoma(POAG)and analyze the diagnostic value of ALFF...AIM:To study the relationships between amplitude of low-frequency fluctuations(ALFF)changes and clinical ophthalmic parameters in patients with primary open angle glaucoma(POAG)and analyze the diagnostic value of ALFF.METHODS:Twenty-four POAG patients and 24 healthy controls(HCs)underwent resting-state functional magnetic resonance imaging(rs-fMRI).Nonparametric rank-sum tests were used to compare the ALFF values in the slow-4 and slow-5 bands,and Spearman or Pearson correlation analysis was used to assess the correlation between ALFF changes and clinical ophthalmic parameters in POAG patients.Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic performance of the ALFF.RESULTS:There were 16 males in POAG patients(median age 48y)and 12 males in HCs(median age 39y).Compared with HCs,POAG patients presented increased or decreased ALFF values in different brain regions,and similar changes were observed in mild POAG patients.The ALFF values were correlated with retinal nerve fiber layer(RNFL)thickness,inner limiting membrane-retinal pigment epithelium thickness changes and the degree of visual field defects.Analysis of the diagnostic value of the ALFF via ROC curves revealed that the right medial frontal gyrus[area under the curve(AUC)=0.9063]and superior frontal gyrus(AUC=0.9097)had better diagnostic value than did the optic disc area(AUC=0.8019),visual field index(VFI%,AUC=0.8988)and macular parameters.CONCLUSION:POAG patients present altered cortical function that is significantly correlated with the optic nerve and retinal thickness and had good diagnostic value,which may reflect the underlying neuropathological mechanism of POAG.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
The effect of acupuncture cooperated with low-frequency repetitive transcranial magnetic stimulation （rTMS） on chronic insomnia was explored. Seventy-eight patients with chronic insomnia were randomly allocated into...The effect of acupuncture cooperated with low-frequency repetitive transcranial magnetic stimulation （rTMS） on chronic insomnia was explored. Seventy-eight patients with chronic insomnia were randomly allocated into two groups： treatment group and control group. In the treatment group, the patients received acupuncture combined with rTMS treatment, and those in the control group were given acupuncture cooperated with sham rTMS treatment, 3 days per week for 4 weeks. Before and after treatment, the primary outcomes including the scores on Insomnia Severity Index （ISI） and Pittsburgh Sleep Quality Index （PSQI） and the secondary outcomes including total sleep time （TST）, sleep onset latency （SOL）, wake after sleep onset （WASO）, sleep efficiency （SE%） recorded by sleeping diary and actigraphy were observed in both groups. Seventy-five participants finished the study （38 in treatment group and 37 in control group respectively）. After treatment, the scores in the two groups were improved significantly, more significantly in the treatment group than in the control group. It can be inferred that acupuncture cooperated with rTMS can effectively improve sleep quality, enhance the quality of life of patients and has less side effects.展开更多
Following acute cerebral ischemia in rats, plasma calcitonin gene-related peptide decreased and the level of serum neuron specific enolase and the volume of the infarction increased. Square-wave and triangular-wave el...Following acute cerebral ischemia in rats, plasma calcitonin gene-related peptide decreased and the level of serum neuron specific enolase and the volume of the infarction increased. Square-wave and triangular-wave electrical stimulation with low or high intensities could increase the plasma calcitonin gene-related peptide, decrease the serum neuron specific enolase and reduce the infarction volume in the brain in rats with cerebral ischemia. There was no significant difference between different wave forms and intensities. The experimental findings indicate that low-frequency electrical stimulation with varying waveforms and intensities can treat acute cerebral ischemia in rats.展开更多
BACKGROUND： Low-frequency repetitive transcranial magnetic stimulation （rTMS） has been shown to significantly reduce epileptiform discharges and control clinical seizures in intractable epilepsy patients. The locat...BACKGROUND： Low-frequency repetitive transcranial magnetic stimulation （rTMS） has been shown to significantly reduce epileptiform discharges and control clinical seizures in intractable epilepsy patients. The location of epileptic foci and magnetic stimulation sites remain uncertain. The effects of rTMS on electroencephalogram and seizure remain unclear in epileptic patients following dipole source localization. OBJECTIVE： To investigate the effects of low-frequency rTMS on electroencephalogram and seizure in temporal lobe epilepsy patients after dipole source localization. DESIGN, TIME AND SETTING： The randomized, controlled study was performed at the outpatient clinic Department of Neurology, Hospital Affiliated to North Sichuan Medical College from December 2003 to February 2007. PARTICIPANTS： A total of 30 temporal lobe epilepsy patients, comprising 19 males and 11 females, aged 1749 years, presented with epileptiform discharges and were enrolled for this study. Disease course ranged between 1-6 years, with 1-5 seizures per month. Imaging examinations revealed 11 patients with structural changes in the brain. The patients were randomly and equally assigned into drug treatment and transcranial magnetic stimulation （TMS） groups. METHODS： Patients in the drug treatment group were orally treated with carbamazepine. Patients in the TMS group received oral carbamazepine treatment of and TMS. A Maglite-r25 magnetic stimulator （Dantec Dynamics, Denmark） was used to stimulate epileptic foci in the temporal lobe following electroencephalogram dipole localization （1 Hz, 90% threshold intensity, at a stimulation frequency of 500 times, once a day, for 7 days）. MAIN OUTCOME MEASURES： At 30 days after TMS, seizure frequency and rate of epileptiform discharges were observed in patients from both groups. Therapeutic safety was investigated during treatment. RESULTS： Within 30 days of treatment, there were no significant differences in seizure frequency between the TMS group （1.5 ± 0.3） seizures and the drug treatment group [（1.9± 0.4） seizures] （P 〉 0.05）. The rate of epileptiform discharges [27% （4/15）] was significantly less in the TMS group than in the drug treatment group [73% （11/15）] （P 〈 0.05）. During TMS, five patients suffered from transient mild headache, but were completely relieved within 2 hours. CONCLUSION： Low-frequency rTMS exhibited inhibitory effects on epileptiform discharges over a short period of time, and decreased seizure frequency to some degree. Results from the present study suggested that low-frequency rTMS is safe.展开更多
In the aging brain, cognitive function gradually dedines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel ne...In the aging brain, cognitive function gradually dedines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation （〈1 Hz） ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 （both synaptic markers）, to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity （110% average resting motor threshold intensity, 1 Hz） increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.展开更多
BACKGROUND： The postoperative recovery of nerve function in patients with peripheral nerve injury is always an important problem to solve after treatment. The electric stimulation induced electromagnetic field can no...BACKGROUND： The postoperative recovery of nerve function in patients with peripheral nerve injury is always an important problem to solve after treatment. The electric stimulation induced electromagnetic field can nourish nerve, postpone muscular atrophy, and help the postoperative neuromuscular function. OBJECTIVE： To observe the effects of low-frequency pulse percutaneous electric stimulation on the functional recovery of postoperative patients with peripheral nerve injury, and quantitatively evaluate the results of electromyogram （EMG） examination before and after treatment. DESIGN ： A retrospective case analysis SETTING： The Sixth People＇s Hospital affiliated to Shanghai Jiaotong University PARTICIPANTS： Nineteen postoperative inpatients with peripheral nerve injury were selected from the De- partment of Orthopaedics, the Sixth People＇s Hospital affiliated to Shanghai Jiaotong University from June 2005 to January 2006, including 13 males and 6 females aged 24-62 years with an average of 36 years old. There were 3 cases of brachial plexus nerve injury, 3 of median nerve injury, 7 of radial nerve injury, 3 of ul- nar nerve injury and 3 of common peroneal nerve injury, and all the patients received probing nerve fiber restoration. Their main preoperative manifestations were dennervation, pain in limbs, motor and sensory disturbances. All the 19 patients were informed with the therapeutic program and items for evaluation. METHODS： ① Low-frequency pulse percutaneous electric stimulation apparatus： The patients were given electric stimulation with the TERESA cantata instrument （TERESA-0, Shanghai Teresa Health Technology, Co., Ltd.）. The patients were stimulated with symmetric square waves of 1-111 Hz, and the intensity was 1.2-5.0 mA, and it was gradually adjusted according to the recovered conditions of neural regeneration following the principle that the intensity was strong enough and the patients felt no obvious upset. They were treated for 4- 24 weeks, 10-30 minutes for each time, 1-3 times a day, and 6 weeks as a course. ② EMG examination was applied to evaluate the recoveries of recruitment, motor conduction velocity （MCV） and sensory conduction velocity （SCV） before and after treatment. The patients were examined with the EMG apparatus （DIS- A2000C, Danmark） before and after the treatment of percutaneous electric stimulation. ③Standards for evaluating the effects included cured （complete recovery of motor functions, muscle strength of grade 5, no abnormality in EMG examination）, obviously effective [general recovery of motor function, muscle strength of grade 4, no or a few denervation potentials, motor conduction velocity （MCV） and sensory conduction velocity （SCV）], improved （partial recovery of motor function, muscle strength of grade 3, denervation potentials and reinneration potentials, slowed MCV and SCV, invalid （no obvious changes of motor function）. MAIN OUTCOME MEASURES： ① Ameliorated degree of the nerve function of the postoperative patients with peripheral nerve injury treated with percutaneous electric stimulation; ② Changes of EMG examination before and after treatment. RESULTS： All the 19 postoperative patients with peripheral nerve injury were involved in the analysis of results. ① Comparison of nerve function before and after treatment in 19 patients with peripheral nerve injury of different sites： For the patients with radial nerve injury （n=7）, the nerve functions all completely recovered after 8-week treatment, and the cured and obvious rate was 100% （7/7）; For the patients with brachial plexus nerve injury （n=3）, 1 case had no obvious improvement, and the cured and obvious rate was 67% （2/3）; For the patients with common peroneal nerve injury （n=3）, the extension of foot dorsum generally recovered in 1 case of nerve contusion after 4-week treatment, and the cured and obvious rate was 67% （2/3）; For the patients with median nerve injury （n=3）, muscle strength was obviously recovered, and the cured and obvious rate was 100% （3/3）; For the patients with ulnar nerve injury （n=3）, 1 case only had recovery of partial senses, and the cured and obvious rate was 67% （2/3）. Totally 9 cases were cured, 7 were obviously effective, 1 was improved, and only 2 were invalid. After 4 courses, the cured rate of damaged nerve function after four courses was 47% （9/19）, and effective rate was 89% （17/19）.② Comparison of EMG examination before and after treatment： Before and after percutaneous electric stimulation, he effective rates of recruitment, MCV and SCV were 89% （17/19）, 58% （11/19）, 47% （9/19） respectively, and there were extremely obvious differences （P〈 0.01）. CONCLUSION： ①Low-frequency pulse percutaneous electric stimulation can improve the nerve function of postoperative patients with peripheral nerve injury of different sites, especially that the injuries of radial nerve and median nerve recover more obviously. ②Percutaneous electric stimulation can ameliorate the indexes of EMG examination, especially the recruitment, in postoperative patients with peripheral nerve injury.展开更多
The effect of combined low-frequency repetitive transcranial magnetic stimulation（LF r TMS） and virtual reality（VR） training in patients after stroke was assessed. In a double-blind randomized controlled trial, 11...The effect of combined low-frequency repetitive transcranial magnetic stimulation（LF r TMS） and virtual reality（VR） training in patients after stroke was assessed. In a double-blind randomized controlled trial, 112 patients with hemiplegia after stroke were randomly divided into two groups： experimental and control. In experimental group, the patients received LF r TMS and VR training treatment, and those in control group received sham r TMS and VR training treatment. Participants in both groups received therapy of 6 days per week for 4 weeks. The primary endpoint including the upper limb motor function test of Fugl-meyer assessment（U-FMA） and wolf motor function test（WMFT）, and the secondary endpoint including modified Barthel index（MBI） and 36-item Short Form Health Survey Questionnaire（SF-36） were assessed before and 4 weeks after treatment. Totally, 108 subjects completed the study（55 in experimental group and 53 in control group respectively）. After 4-week treatment, the U-FMA scores [mean difference of 13.2, 95% confidence interval（CI） 3.6 to 22.7, P〈0.01], WMFT scores（mean difference of 2.9, 95% CI 2.7 to 12.3, P〈0.01）, and MBI scores（mean difference 16.1, 95% CI 3.8 to 9.4, P〈0.05） were significantly increased in the experimental group as compared with the control group. The results suggested the combined use of LF r TMS with VR training could effectively improve the upper limb function, the living activity, and the quality of life in patients with hemiplegia following subacute stroke, which may provide a better rehabilitation treatment for subacute stroke.展开更多
BAOKGROUND： Bcl-2 and Fas proteins are well known as anti-apoptotic and pro-apoptotic factors respectively. However, whether the anti-epileptic mechanism of low-frequency repetitive transcranial magnetic stimulation ...BAOKGROUND： Bcl-2 and Fas proteins are well known as anti-apoptotic and pro-apoptotic factors respectively. However, whether the anti-epileptic mechanism of low-frequency repetitive transcranial magnetic stimulation （rTMS） involves an anti-apoptotic effect via regulating Bcl-2 and Fas protein expression remains to be determined. OBJECTIVE： To verify the correlation between the anti-epileptic mechanism following pretreatment of low-frequency rTMS and anti-hippocampal apoptosis. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at Institute of Neurological Disorders, Affiliated Hospital of North Sichuan Medical College between September 2007 and March 2008. MATERIALS： Pilocarpine （053K13011） was provided by Sigma, USA; lithium was provided by Shanghai Biotechnology Co., Ltd., China; Dantec Maglite-r25 rTMS instrument was provided by Dundee, Denmark. METHODS： A total of 21 adult male Wistar rats were randomly divided into control （n = 6）, rTMS pretreatment （n = 9）, and sham-stimulation （n = 6） groups. The rTMS pretreatment group was pretreated with low-frequency rTMS （0.5 Hz, 75% threshold intensity, 20 times/bundle, and 5 bundles/day）, while the sham-stimulation group was sham-stimulated with a similar sound for 7 successive days to establish lithium-pilocarpine-induced epileptic state models. MAIN OUTCOME MEASURES： Epileptic stroke latency; neuronal morphology was observed using hematoxylin and eosin staining; mean positive-reactive cell number and mean absorbance of Bcl-2 and Fas protein in the hippocampal CA1 region was observed using immunohistochemistry. RESULTS： Epileptic latency in the rTMS pretreatment group was significantly enhanced （P 〈 0.01）, and a number of degenerated neurons were observed to be apoptotic. Bcl-2 protein expression increased at each time point, but Fas protein expression decreased （P 〈 0.01）. CONCLUSION： Low-frequency rTMS has an anti-epileptic effect, which may be via regulation of Bcl-2 and Fas protein expression in the hippocampal region.展开更多
Short-term, low-frequency electrical stimulation of neural tissues significantly enhances axonal regeneration of peripheral nerves following injury. However, little is known about the mechanisms of electrical stimulat...Short-term, low-frequency electrical stimulation of neural tissues significantly enhances axonal regeneration of peripheral nerves following injury. However, little is known about the mechanisms of electrical stimulation to induce neurite outgrowth. In the present study, short-term, low-frequency electrical stimulation, using identical stimulation parameters of in vivo experiments, was administered to in vitro dorsal root ganglion （DRG） neurons. Enhanced neurite outgrowth, as well as synthesis and release of brain-derived neurotrophic factor （BDNF）, were examined in electrical stimulation-treated DRG neuronal cultures. Because the effects of electrical stimulation on neuronal intracellular signaling molecules are less reported, classic calcium intracellular signals are directly or indirectly involved in electrical stimulation effects on neurons. Cultured DRG neurons were pretreated with the calcium channel blocker nifedipine, followed by electrical stimulation. Results suggested that electrical stimulation not only promoted in vitro neurite outgrowth, but also enhanced BDNF expression. However, nifedipine reduced electrical stimulation-enhanced neurite outgrowth and BDNF biosynthesis. These results suggest that the promoting effects of electrical stimulation on DRG neurite outgrowth could be associated with altered calcium influx, which is involved induction of neuronal BDNF expression and secretion.展开更多
Low-frequency electrical stimulation has resulted in favorable effects in the treatment of post-stroke dysphagia. However, the safety of cervical low-frequency electrical stimulation remains unclear because of numerou...Low-frequency electrical stimulation has resulted in favorable effects in the treatment of post-stroke dysphagia. However, the safety of cervical low-frequency electrical stimulation remains unclear because of numerous nerves and blood vessels in the neck. In the present study, rats with ischemic stroke underwent low-frequency electrical stimulation, and systemic and local effects of electrical stimulation at different densities and waveforms were investigated. Electrical stimulation resulted in no significant effects on body mass, liver or kidney function, or mortality rate. In addition, no significant adverse reaction was observed, despite overly high intensity of low-frequency electrical stimulation, which induced laryngismus, results from the present study suggested that it is safe to stimulate the neck with a low-frequency electricity under certain intensities.展开更多
Objective: to explore the effect of balloon dilatation combined with low-frequency electrical stimulation on dysphagia in brainstem infarction. Methods: A total of 60 cases were included in this study. They were divid...Objective: to explore the effect of balloon dilatation combined with low-frequency electrical stimulation on dysphagia in brainstem infarction. Methods: A total of 60 cases were included in this study. They were divided into group 1 and group 2, which were respectively the observation group and the control group. The former was treated with combined therapy, while the latter was treated with separate therapy. Results: according to the results in Table 4 and Table 5, the results of each index in the observation group are better than those in the control group, indicating that the combination therapy and the single therapy are more advantageous, and the comparison with P < 0.05 is statistically significant. Conclusion: balloon dilation combined with low-frequency electrical stimulation has a significant effect on dysphagia in brainstem infarction. Compared with simple swallowing function training, balloon dilation can improve patients' swallowing function, which is worthy of research and promotion.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
Transcutaneous electrical acupoint stimulation(TEAS)is a kind of physical therapy that use electric cur-rent through the electrodes placed on the surface of acupoints to produce clinical effects in the human body,whic...Transcutaneous electrical acupoint stimulation(TEAS)is a kind of physical therapy that use electric cur-rent through the electrodes placed on the surface of acupoints to produce clinical effects in the human body,which is characterized by less adverse reaction and convenient operation.It has been widely used in the treatment of various diseases.This review introduces six major clinical applications of TEAS,named analgesia,regulation of gastrointestinal function,improvement of reproductive function,enhancement of cognitive function,promotion of limb function recovery and relief of fatigue.Besides,TEAS has been ap-plied to the treatment of other chronic diseases such as hypertension and diabetes,achieving satisfactory clinical effects.However,two crucial challenges are encountered in the development of TEAS.One is the lack of standardization in the selection of parameters such as waveform,frequency,intensity and stimula-tion duration.The other is the limitation on the flexibility in the acupoint selection.This review analyzes key issues that need to be addressed in the current clinical application of TEAS,such as the selection of parameters and acupoints,and this review provides a certain reference value for optimizing regimens of TEAS and promoting its development and application.展开更多
基金supported by grants from the National Natural Science Foundation of China(U21A20418 and 82173796)the Natural Science Foundation of Zhejiang Province(LD22H310003)the Research Project of Zhejiang Chinese Medical University(2023JKZDZC04).
文摘Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary focus.It is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy,but still lacks effective treatments.Here,we aimed to test the effects of low-frequency stimulation(LFS)at the subiculum for secondary epileptogenesis in a mouse model.Here,secondary epileptogenesis was simulated at regions both contralateral and ipsilateral to the primary focus by applying successive kindling stimuli.Mice kindled at the right CA3 showed higher seizure susceptibilities at both the contralateral CA3 and the ipsilateral entorhinal cortex and had accelerated kindling processes compared with naive mice.LFS at the ipsilateral subiculum during the primary kindling progress at the right CA3 effectively prevented secondary epileptogenesis at both the contralateral CA3 and the ipsilateral entorhinal cortex,characterized by decreased seizure susceptibilities and a retarded kindling process at those secondary foci.Only application along with the primary epileptogenesis was effective.Notably,the effects of LFS on secondary epileptogenesis were associated with its inhibitory effect at the secondary focus through interfering with the enhancement of synaptic connections between the primary and secondary foci.These results imply that LFS at the subiculum is an effective preventive strategy for extensive secondary epileptogenesis in temporal lobe epilepsy and present the subiculum as a target with potential translational importance.
文摘Since the last decade deep brain stimulation has been proposed as an alternative treatment for patients who do not become seizure-free with the current pharmacological treatments and cannot undergo resective surgical procedure. However, the optimal stimulation parameters remain undetermined and active research in humans and animals is necessary. The present study was designed to investigate the effect of unilateral Low Frequency Stimulation (LFS) of hippocampus on seizure development by using the hippocampal rapid kindling method (hRK) in rats. We used male Wistar rats implanted with electrodes in the ventral hippocampus. All rats underwent hRK (biphasic square wave pulses, 20 Hz for 10 seconds) during three consecutive days (twelve stimulations per day). The control group (hRK;n = 6) received only RK stimulus, while the treated group (LFS-hRK;n = 8) received also LFS (biphasic square wave pulses, 1 Hz for 30 seconds) immediately before the RK stimulus, during three consecutive days. At the end of behavioral testing on day 3, 62% (P < 0.05) of the animals receiving LFS treatment were still not fully kindled staying in stages 0-III (P < 0.01). The number of stimulations needed to achieve generalized seizures (stage IV-V of Racine scale) was significantly higher (P < 0.05) in the LFS group with respect to control group. No significant differences in the cumulative daily afterdischarge duration were observed between both groups. These findings suggest that preemptive LFS can significantly decrease the incidence of hippocampus-kindled seizures and delay the progression and secondary generalization of focal seizures.
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 National Natural Science Foundation of China(No.82260203).
文摘AIM:To study the relationships between amplitude of low-frequency fluctuations(ALFF)changes and clinical ophthalmic parameters in patients with primary open angle glaucoma(POAG)and analyze the diagnostic value of ALFF.METHODS:Twenty-four POAG patients and 24 healthy controls(HCs)underwent resting-state functional magnetic resonance imaging(rs-fMRI).Nonparametric rank-sum tests were used to compare the ALFF values in the slow-4 and slow-5 bands,and Spearman or Pearson correlation analysis was used to assess the correlation between ALFF changes and clinical ophthalmic parameters in POAG patients.Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic performance of the ALFF.RESULTS:There were 16 males in POAG patients(median age 48y)and 12 males in HCs(median age 39y).Compared with HCs,POAG patients presented increased or decreased ALFF values in different brain regions,and similar changes were observed in mild POAG patients.The ALFF values were correlated with retinal nerve fiber layer(RNFL)thickness,inner limiting membrane-retinal pigment epithelium thickness changes and the degree of visual field defects.Analysis of the diagnostic value of the ALFF via ROC curves revealed that the right medial frontal gyrus[area under the curve(AUC)=0.9063]and superior frontal gyrus(AUC=0.9097)had better diagnostic value than did the optic disc area(AUC=0.8019),visual field index(VFI%,AUC=0.8988)and macular parameters.CONCLUSION:POAG patients present altered cortical function that is significantly correlated with the optic nerve and retinal thickness and had good diagnostic value,which may reflect the underlying neuropathological mechanism of POAG.
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The effect of acupuncture cooperated with low-frequency repetitive transcranial magnetic stimulation （rTMS） on chronic insomnia was explored. Seventy-eight patients with chronic insomnia were randomly allocated into two groups： treatment group and control group. In the treatment group, the patients received acupuncture combined with rTMS treatment, and those in the control group were given acupuncture cooperated with sham rTMS treatment, 3 days per week for 4 weeks. Before and after treatment, the primary outcomes including the scores on Insomnia Severity Index （ISI） and Pittsburgh Sleep Quality Index （PSQI） and the secondary outcomes including total sleep time （TST）, sleep onset latency （SOL）, wake after sleep onset （WASO）, sleep efficiency （SE%） recorded by sleeping diary and actigraphy were observed in both groups. Seventy-five participants finished the study （38 in treatment group and 37 in control group respectively）. After treatment, the scores in the two groups were improved significantly, more significantly in the treatment group than in the control group. It can be inferred that acupuncture cooperated with rTMS can effectively improve sleep quality, enhance the quality of life of patients and has less side effects.
基金the National High-Tech R&D Program of China (863 Program),No.2007AA022Z482
文摘Following acute cerebral ischemia in rats, plasma calcitonin gene-related peptide decreased and the level of serum neuron specific enolase and the volume of the infarction increased. Square-wave and triangular-wave electrical stimulation with low or high intensities could increase the plasma calcitonin gene-related peptide, decrease the serum neuron specific enolase and reduce the infarction volume in the brain in rats with cerebral ischemia. There was no significant difference between different wave forms and intensities. The experimental findings indicate that low-frequency electrical stimulation with varying waveforms and intensities can treat acute cerebral ischemia in rats.
基金the Youth Foundation Program of Sichuan Province,No.04ZQ026-010
文摘BACKGROUND： Low-frequency repetitive transcranial magnetic stimulation （rTMS） has been shown to significantly reduce epileptiform discharges and control clinical seizures in intractable epilepsy patients. The location of epileptic foci and magnetic stimulation sites remain uncertain. The effects of rTMS on electroencephalogram and seizure remain unclear in epileptic patients following dipole source localization. OBJECTIVE： To investigate the effects of low-frequency rTMS on electroencephalogram and seizure in temporal lobe epilepsy patients after dipole source localization. DESIGN, TIME AND SETTING： The randomized, controlled study was performed at the outpatient clinic Department of Neurology, Hospital Affiliated to North Sichuan Medical College from December 2003 to February 2007. PARTICIPANTS： A total of 30 temporal lobe epilepsy patients, comprising 19 males and 11 females, aged 1749 years, presented with epileptiform discharges and were enrolled for this study. Disease course ranged between 1-6 years, with 1-5 seizures per month. Imaging examinations revealed 11 patients with structural changes in the brain. The patients were randomly and equally assigned into drug treatment and transcranial magnetic stimulation （TMS） groups. METHODS： Patients in the drug treatment group were orally treated with carbamazepine. Patients in the TMS group received oral carbamazepine treatment of and TMS. A Maglite-r25 magnetic stimulator （Dantec Dynamics, Denmark） was used to stimulate epileptic foci in the temporal lobe following electroencephalogram dipole localization （1 Hz, 90% threshold intensity, at a stimulation frequency of 500 times, once a day, for 7 days）. MAIN OUTCOME MEASURES： At 30 days after TMS, seizure frequency and rate of epileptiform discharges were observed in patients from both groups. Therapeutic safety was investigated during treatment. RESULTS： Within 30 days of treatment, there were no significant differences in seizure frequency between the TMS group （1.5 ± 0.3） seizures and the drug treatment group [（1.9± 0.4） seizures] （P 〉 0.05）. The rate of epileptiform discharges [27% （4/15）] was significantly less in the TMS group than in the drug treatment group [73% （11/15）] （P 〈 0.05）. During TMS, five patients suffered from transient mild headache, but were completely relieved within 2 hours. CONCLUSION： Low-frequency rTMS exhibited inhibitory effects on epileptiform discharges over a short period of time, and decreased seizure frequency to some degree. Results from the present study suggested that low-frequency rTMS is safe.
基金supported by the Natural Science Foundation of Hebei Province of China,No.H2015206409Science and Technology Research Youth Fund Project of Hebei Colleges and Universities in China,No.QN20131068,QN2014140+1 种基金a grant from Health and Family Planning Commission Medical Scientific Research Project in Hebei Province of China,No.ZL20140017a grant from Hebei Science and Technology Support Program Project of China,No.132777209,132777135
文摘In the aging brain, cognitive function gradually dedines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation （〈1 Hz） ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 （both synaptic markers）, to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity （110% average resting motor threshold intensity, 1 Hz） increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function.
基金grants from Sci-entific Research Fund of theMinistry of Health, No.20040801 Shanghai Ris-ing-Star Program of Technologi-cal Committee, No.05QMX1438
文摘BACKGROUND： The postoperative recovery of nerve function in patients with peripheral nerve injury is always an important problem to solve after treatment. The electric stimulation induced electromagnetic field can nourish nerve, postpone muscular atrophy, and help the postoperative neuromuscular function. OBJECTIVE： To observe the effects of low-frequency pulse percutaneous electric stimulation on the functional recovery of postoperative patients with peripheral nerve injury, and quantitatively evaluate the results of electromyogram （EMG） examination before and after treatment. DESIGN ： A retrospective case analysis SETTING： The Sixth People＇s Hospital affiliated to Shanghai Jiaotong University PARTICIPANTS： Nineteen postoperative inpatients with peripheral nerve injury were selected from the De- partment of Orthopaedics, the Sixth People＇s Hospital affiliated to Shanghai Jiaotong University from June 2005 to January 2006, including 13 males and 6 females aged 24-62 years with an average of 36 years old. There were 3 cases of brachial plexus nerve injury, 3 of median nerve injury, 7 of radial nerve injury, 3 of ul- nar nerve injury and 3 of common peroneal nerve injury, and all the patients received probing nerve fiber restoration. Their main preoperative manifestations were dennervation, pain in limbs, motor and sensory disturbances. All the 19 patients were informed with the therapeutic program and items for evaluation. METHODS： ① Low-frequency pulse percutaneous electric stimulation apparatus： The patients were given electric stimulation with the TERESA cantata instrument （TERESA-0, Shanghai Teresa Health Technology, Co., Ltd.）. The patients were stimulated with symmetric square waves of 1-111 Hz, and the intensity was 1.2-5.0 mA, and it was gradually adjusted according to the recovered conditions of neural regeneration following the principle that the intensity was strong enough and the patients felt no obvious upset. They were treated for 4- 24 weeks, 10-30 minutes for each time, 1-3 times a day, and 6 weeks as a course. ② EMG examination was applied to evaluate the recoveries of recruitment, motor conduction velocity （MCV） and sensory conduction velocity （SCV） before and after treatment. The patients were examined with the EMG apparatus （DIS- A2000C, Danmark） before and after the treatment of percutaneous electric stimulation. ③Standards for evaluating the effects included cured （complete recovery of motor functions, muscle strength of grade 5, no abnormality in EMG examination）, obviously effective [general recovery of motor function, muscle strength of grade 4, no or a few denervation potentials, motor conduction velocity （MCV） and sensory conduction velocity （SCV）], improved （partial recovery of motor function, muscle strength of grade 3, denervation potentials and reinneration potentials, slowed MCV and SCV, invalid （no obvious changes of motor function）. MAIN OUTCOME MEASURES： ① Ameliorated degree of the nerve function of the postoperative patients with peripheral nerve injury treated with percutaneous electric stimulation; ② Changes of EMG examination before and after treatment. RESULTS： All the 19 postoperative patients with peripheral nerve injury were involved in the analysis of results. ① Comparison of nerve function before and after treatment in 19 patients with peripheral nerve injury of different sites： For the patients with radial nerve injury （n=7）, the nerve functions all completely recovered after 8-week treatment, and the cured and obvious rate was 100% （7/7）; For the patients with brachial plexus nerve injury （n=3）, 1 case had no obvious improvement, and the cured and obvious rate was 67% （2/3）; For the patients with common peroneal nerve injury （n=3）, the extension of foot dorsum generally recovered in 1 case of nerve contusion after 4-week treatment, and the cured and obvious rate was 67% （2/3）; For the patients with median nerve injury （n=3）, muscle strength was obviously recovered, and the cured and obvious rate was 100% （3/3）; For the patients with ulnar nerve injury （n=3）, 1 case only had recovery of partial senses, and the cured and obvious rate was 67% （2/3）. Totally 9 cases were cured, 7 were obviously effective, 1 was improved, and only 2 were invalid. After 4 courses, the cured rate of damaged nerve function after four courses was 47% （9/19）, and effective rate was 89% （17/19）.② Comparison of EMG examination before and after treatment： Before and after percutaneous electric stimulation, he effective rates of recruitment, MCV and SCV were 89% （17/19）, 58% （11/19）, 47% （9/19） respectively, and there were extremely obvious differences （P〈 0.01）. CONCLUSION： ①Low-frequency pulse percutaneous electric stimulation can improve the nerve function of postoperative patients with peripheral nerve injury of different sites, especially that the injuries of radial nerve and median nerve recover more obviously. ②Percutaneous electric stimulation can ameliorate the indexes of EMG examination, especially the recruitment, in postoperative patients with peripheral nerve injury.
文摘The effect of combined low-frequency repetitive transcranial magnetic stimulation（LF r TMS） and virtual reality（VR） training in patients after stroke was assessed. In a double-blind randomized controlled trial, 112 patients with hemiplegia after stroke were randomly divided into two groups： experimental and control. In experimental group, the patients received LF r TMS and VR training treatment, and those in control group received sham r TMS and VR training treatment. Participants in both groups received therapy of 6 days per week for 4 weeks. The primary endpoint including the upper limb motor function test of Fugl-meyer assessment（U-FMA） and wolf motor function test（WMFT）, and the secondary endpoint including modified Barthel index（MBI） and 36-item Short Form Health Survey Questionnaire（SF-36） were assessed before and 4 weeks after treatment. Totally, 108 subjects completed the study（55 in experimental group and 53 in control group respectively）. After 4-week treatment, the U-FMA scores [mean difference of 13.2, 95% confidence interval（CI） 3.6 to 22.7, P〈0.01], WMFT scores（mean difference of 2.9, 95% CI 2.7 to 12.3, P〈0.01）, and MBI scores（mean difference 16.1, 95% CI 3.8 to 9.4, P〈0.05） were significantly increased in the experimental group as compared with the control group. The results suggested the combined use of LF r TMS with VR training could effectively improve the upper limb function, the living activity, and the quality of life in patients with hemiplegia following subacute stroke, which may provide a better rehabilitation treatment for subacute stroke.
基金Youth Foundation Project of Sichuan Province, No. 04ZQ026-010
文摘BAOKGROUND： Bcl-2 and Fas proteins are well known as anti-apoptotic and pro-apoptotic factors respectively. However, whether the anti-epileptic mechanism of low-frequency repetitive transcranial magnetic stimulation （rTMS） involves an anti-apoptotic effect via regulating Bcl-2 and Fas protein expression remains to be determined. OBJECTIVE： To verify the correlation between the anti-epileptic mechanism following pretreatment of low-frequency rTMS and anti-hippocampal apoptosis. DESIGN, TIME AND SETTING： A randomized controlled animal experiment was performed at Institute of Neurological Disorders, Affiliated Hospital of North Sichuan Medical College between September 2007 and March 2008. MATERIALS： Pilocarpine （053K13011） was provided by Sigma, USA; lithium was provided by Shanghai Biotechnology Co., Ltd., China; Dantec Maglite-r25 rTMS instrument was provided by Dundee, Denmark. METHODS： A total of 21 adult male Wistar rats were randomly divided into control （n = 6）, rTMS pretreatment （n = 9）, and sham-stimulation （n = 6） groups. The rTMS pretreatment group was pretreated with low-frequency rTMS （0.5 Hz, 75% threshold intensity, 20 times/bundle, and 5 bundles/day）, while the sham-stimulation group was sham-stimulated with a similar sound for 7 successive days to establish lithium-pilocarpine-induced epileptic state models. MAIN OUTCOME MEASURES： Epileptic stroke latency; neuronal morphology was observed using hematoxylin and eosin staining; mean positive-reactive cell number and mean absorbance of Bcl-2 and Fas protein in the hippocampal CA1 region was observed using immunohistochemistry. RESULTS： Epileptic latency in the rTMS pretreatment group was significantly enhanced （P 〈 0.01）, and a number of degenerated neurons were observed to be apoptotic. Bcl-2 protein expression increased at each time point, but Fas protein expression decreased （P 〈 0.01）. CONCLUSION： Low-frequency rTMS has an anti-epileptic effect, which may be via regulation of Bcl-2 and Fas protein expression in the hippocampal region.
基金the Shanghai Leading Academic Discipline Project,No.S30201the Doctoral Research Foundation of Nanchang University
文摘Short-term, low-frequency electrical stimulation of neural tissues significantly enhances axonal regeneration of peripheral nerves following injury. However, little is known about the mechanisms of electrical stimulation to induce neurite outgrowth. In the present study, short-term, low-frequency electrical stimulation, using identical stimulation parameters of in vivo experiments, was administered to in vitro dorsal root ganglion （DRG） neurons. Enhanced neurite outgrowth, as well as synthesis and release of brain-derived neurotrophic factor （BDNF）, were examined in electrical stimulation-treated DRG neuronal cultures. Because the effects of electrical stimulation on neuronal intracellular signaling molecules are less reported, classic calcium intracellular signals are directly or indirectly involved in electrical stimulation effects on neurons. Cultured DRG neurons were pretreated with the calcium channel blocker nifedipine, followed by electrical stimulation. Results suggested that electrical stimulation not only promoted in vitro neurite outgrowth, but also enhanced BDNF expression. However, nifedipine reduced electrical stimulation-enhanced neurite outgrowth and BDNF biosynthesis. These results suggest that the promoting effects of electrical stimulation on DRG neurite outgrowth could be associated with altered calcium influx, which is involved induction of neuronal BDNF expression and secretion.
基金supported by the National High Technology Research and Development Program of China(The development and application of novel techniques for cerebrovascular disease rehabilitation),No.2007AA02Z482
文摘Low-frequency electrical stimulation has resulted in favorable effects in the treatment of post-stroke dysphagia. However, the safety of cervical low-frequency electrical stimulation remains unclear because of numerous nerves and blood vessels in the neck. In the present study, rats with ischemic stroke underwent low-frequency electrical stimulation, and systemic and local effects of electrical stimulation at different densities and waveforms were investigated. Electrical stimulation resulted in no significant effects on body mass, liver or kidney function, or mortality rate. In addition, no significant adverse reaction was observed, despite overly high intensity of low-frequency electrical stimulation, which induced laryngismus, results from the present study suggested that it is safe to stimulate the neck with a low-frequency electricity under certain intensities.
文摘Objective: to explore the effect of balloon dilatation combined with low-frequency electrical stimulation on dysphagia in brainstem infarction. Methods: A total of 60 cases were included in this study. They were divided into group 1 and group 2, which were respectively the observation group and the control group. The former was treated with combined therapy, while the latter was treated with separate therapy. Results: according to the results in Table 4 and Table 5, the results of each index in the observation group are better than those in the control group, indicating that the combination therapy and the single therapy are more advantageous, and the comparison with P < 0.05 is statistically significant. Conclusion: balloon dilation combined with low-frequency electrical stimulation has a significant effect on dysphagia in brainstem infarction. Compared with simple swallowing function training, balloon dilation can improve patients' swallowing function, which is worthy of research and promotion.
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.
基金Supported by Shanghai 2020“Science and Technology Innovation Action Plan”Medical Innovation Research Special Program:20Y21902800Shanghai Municipal Health Commission Shanghai Three-Year Action Plan to Further Accelerate the Development of Traditional Chinese Medicine Inheritance and Innovation:ZY(2021-2023)−0302)+1 种基金Shanghai Key Specialty(Acupuncture)Construction Project:shslczdzk04701Shanghai 2024"Science and Technology Innovation Action Plan"star cultivation(Sail special):24YF2740600.
文摘Transcutaneous electrical acupoint stimulation(TEAS)is a kind of physical therapy that use electric cur-rent through the electrodes placed on the surface of acupoints to produce clinical effects in the human body,which is characterized by less adverse reaction and convenient operation.It has been widely used in the treatment of various diseases.This review introduces six major clinical applications of TEAS,named analgesia,regulation of gastrointestinal function,improvement of reproductive function,enhancement of cognitive function,promotion of limb function recovery and relief of fatigue.Besides,TEAS has been ap-plied to the treatment of other chronic diseases such as hypertension and diabetes,achieving satisfactory clinical effects.However,two crucial challenges are encountered in the development of TEAS.One is the lack of standardization in the selection of parameters such as waveform,frequency,intensity and stimula-tion duration.The other is the limitation on the flexibility in the acupoint selection.This review analyzes key issues that need to be addressed in the current clinical application of TEAS,such as the selection of parameters and acupoints,and this review provides a certain reference value for optimizing regimens of TEAS and promoting its development and application.
