Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimul...Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson’s disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity(up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity(Unified Parkinson’s Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy,and warrant future experimental investigation to validate its clinical utility.展开更多
Deep brain stimulation （DBS） is an effective technique for treating Parkinson＇s disease （PD） in the middle and advanced stages. The subthalamic nucleus （STN） is the most common target for clinical treatment usi...Deep brain stimulation （DBS） is an effective technique for treating Parkinson＇s disease （PD） in the middle and advanced stages. The subthalamic nucleus （STN） is the most common target for clinical treatment using DBS. While STN-DBS can significantly improve motor symptoms in PD patients, adverse cognitive effects have also been reported. The specific effects of STN-DBS on cognitive function and the related mechanisms remain unclear. Thus, it is imperative to identify the influence of STN-DBS on cognition and investigate the potential mechanisms to provide a clearer view of the various cognitive sequelae in PD patients. For this review, a literature search was performed using the following inclusion criteria： （1） at least 10 patients followed for a mean of at least 6 months after surgery since the year 2006; （2） pre- and postoperative cognitive data using at least one standardized neuropsychological scale; and （3） adequate reporting of study results using means and standard deviations. Of -170 clinical studies identified, 25 cohort studies （including 15 self-controlled studies, nine intergroup controlled studies, and one multi-center, randomized control experiment） and one meta- analysis were eligible for inclusion. The results suggest that the precise mechanism of the changes in cognitive function after STN-DBS remains obscure, but STN-DBS certainly has effects on cognition. In particular, a progressive decrease in verbal fluency after STN-DBS is consistently reported and although executive function is unchanged in the intermediate stage postoperatively, it tends to decline in the early and later stages. However, these changes do not affect the improvements in quality of life. STN-DBS seems to be safe with respect to cognitive effects in carefully-selected patients during a follow-up period from 6 months to 9 years.展开更多
There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nuc...There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.展开更多
Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carr...Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carrying the neuropeptide Y gene was transfected into brain tissue of rats with kainic acid-induced epilepsy through stereotactic methods. Following these transfections, we verified overexpression of the neuropeptide Y gene in the epileptic brain. Electroencephalograms showed that seizure severity was significantly inhibited and seizure latency was significantly prolonged up to 4 weeks after gene transfection. Moreover, quantitative fluorescent PCR and western blot assays revealed that the mRNA and protein expression of the N-methyI-D-aspartate receptor subunits NR1, NR2A, and NR2B was inhibited in the hippocampus of epileptic rats. These findings indicate that neuropeptide Y may inhibit seizures via down-regulation of the functional expression of N-methyI-D-aspartate receptors.展开更多
The activity of the Schaffer collaterals of hippocampal CA3 neurons and hippocampal CA1 neurons has been shown to increase after lfuid percussion injury. Diazepam can inhibit the hy-perexcitability of rat hippocampal ...The activity of the Schaffer collaterals of hippocampal CA3 neurons and hippocampal CA1 neurons has been shown to increase after lfuid percussion injury. Diazepam can inhibit the hy-perexcitability of rat hippocampal neurons after injury, but the mechanism by which it affects excitatory synaptic transmission remains poorly understood. Our results showed that diazepam treatment signiifcantly increased the slope of input-output curves in rat neurons after lfuid per-cussion injury. Diazepam signiifcantly decreased the numbers of spikes evoked by super stimuli in the presence of 15 μmol/L bicuculline, indicating the existence of inhibitory pathways in the injured rat hippocampus. Diazepam effectively increased the paired-pulse facilitation ratio in the hippocampal CA1 region following fluid percussion injury, reduced miniature excitatory postsynaptic potentials, decreased action-potential-dependent glutamine release, and reversed spontaneous glutamine release. These data suggest that diazepam could decrease the lfuid per-cussion injury-induced enhancement of excitatory synaptic transmission in the rat hippocampal CA1 area.展开更多
BACKGROUND Implant vagus nerve stimulation is an adjunctive treatment for intractable epilepsy when patients are not suitable for resective surgery.AIM To identify the safety and efficacy of vagus nerve stimulation in...BACKGROUND Implant vagus nerve stimulation is an adjunctive treatment for intractable epilepsy when patients are not suitable for resective surgery.AIM To identify the safety and efficacy of vagus nerve stimulation in children with intractable epilepsy and analyze the effects on different epilepsy syndromes.METHODS Eligible children with intractable epilepsy were admitted to the study.We collected data from preoperative assessments as the baseline.During the followup time,we recorded the process of seizures(frequency,duration,and seizure type),the changes of drugs or parameters,the complications,etc.The mean reduction rate of seizures,response rate,and McHugh scale were chosen as the outcomes.RESULTS A total of 213 patients were implanted with Tsinghua Pins vagus nerve stimulators,and the average age was 6.6 years.In the follow-up time of postoperative 3 mo,6 mo,12 mo,18 mo,and 24 mo,the average reduction rate was 30.2%,49.5%,56.3%,59.4%,and 63.2%,while the response rate was 21.8%,62.5%,57.1%,69.2%,and 70.7%.In addition,implanted vagus nerve stimulation had different effects on epilepsy syndromes.The reduction rate of West syndrome increased from 36.4%(postoperative 6 m)to 74.3%(postoperative 24 m).The reduction rate of Lennox-Gastaut syndrome improved from 25.4%to 73.1%in 24 mo.The chi-square test of the five efficacy grades showed P<0.05.The comparison between the 3-mo follow-up and the 6-mo follow-up showed P<0.05,and the comparison between the 6-mo follow-up and the 24-mo follow-up showed P>0.05.CONCLUSION Vagus nerve stimulation is safe and effective in children with intractable epilepsy,and the seizure reduction occurred in a time-dependent manner.Moreover,patients with West syndrome may get the most benefits.展开更多
BACKGROUND： Deep-brain stimulation has proven to be beneficial in the treatment of Parkinson＇s disease （PD） patients. OBJECTIVE： To investigate the effects of high-frequency stimulation （HFS） to the subthalamic...BACKGROUND： Deep-brain stimulation has proven to be beneficial in the treatment of Parkinson＇s disease （PD） patients. OBJECTIVE： To investigate the effects of high-frequency stimulation （HFS） to the subthalamic nucleus （STN） on neuronal apoptosis and apoptosis-related gene expression in the substantia nigra pars compacta, and to analyze the neuroprotective effect of HFS-STN. DESIGN, TIME AND SETTING： Neuronal morphology experiments were performed in the Beijing Neurosurgical Institute from May to December in 2005. MATERIALS： Forty healthy, adult, Sprague Dawley rats were used to establish a PD model with a unilateral microinjection of 6-hydroxydopamine into two target areas of the right medial forebrain bundle. 6-hydroxydopamine was purchased from Sigma （USA）; high-frequency electrical stimulator was produced by World Precision Instruments （USA）; Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） kit was a product of Nanjing Jiancheng Technology Co., Ltd. （China）; and Bcl-2 and Bax protein assay kit were purchased from Wuhan Boster Bioengineering Co., Ltd. （China）. METHODS： Forty rats were randomly divided into three groups. The stimulation group （n = 15） received HFS-STN on the day of PD modeling. The PD model group （n = 15） was used to establish the PD model. The control group （n = 10） was injected with normal saline containing 0.2 g/L ascorbic acid into two areas of the right medial forebrain bundle. MAIN OUTCOME MEASURES： Survival of dopaminergic neurons in the substantia nigra pars compacta was determined using Nissl staining. Apoptosis of dopaminergic neurons was detected using TUNEL techniques. Expression of anti-apoptotic protein, Bcl-2, and pro-apoptotic protein, Bax, were assayed by immunohistochemistry. RESULTS： Following 6-hydroxydopamine injection, the number of substantia nigra pars compacta neurons was reduced in the stimulation and PD model groups, compared to the control group. At 2 and 4 weeks post-surgery, the grey value of Nissl stained images was significantly less in the PD model and stimulation groups （P 〈 0.05）, and the stimulation group exhibited greater grey values compared to the model group （P 〈 0.05）. At 2 and 4 weeks post-surgery, the number of apoptotic neurons was significantly less in the stimulation group compared to the model group （P 〈 0.05）. In addition, Bcl-2 and Bax expression, as well as the Bcl-2/Bax ratio, was much higher in the stimulation group compared to the model group （P 〈 0.05）. CONCLUSION： HFS-STN has a neuroprotective effect on dopaminergic neurons in the substantia nigra pars compacta of PD rats by promoting Bcl-2 expression, inhibiting Bax expression, and reducing the number of apoptotic dopaminergic neurons.展开更多
Objective: Anger attacks have been observed in patients with obsessive-compulsive disorder(OCD), often triggered by obsessional triggers. However, few studies have reported the clinical characteristics and correlates ...Objective: Anger attacks have been observed in patients with obsessive-compulsive disorder(OCD), often triggered by obsessional triggers. However, few studies have reported the clinical characteristics and correlates of anger attacks among Chinese patients with OCD. Methods: A total of 90 adults with a primary diagnosis of OCD, ranging from 15 to 78 years old, participated in the study. Participants were administered the Rage Outbursts and Anger Rating Scale(ROARS), Yale-Brown Obsessive-Compulsive Scale-Second Edition, and Brown Assessment of Beliefs Scale by a trained clinician. Patients completed the Obsessive-Compulsive Inventory-Revised and Depression Anxiety Stress Scale-21. Results: A total of 31.3% of participants reported anger outbursts in the past week, and ROARS scores had no significant correlation with age, duration of illness, OCD severity, depression, or stress. However, ROARS scores were negatively related to education level, and positively related to obsessing symptoms and anxiety. Conclusions: These data suggest that anger attacks are relatively common in Chinese patients with OCD. The severity of anger attacks is related to educational level, obsessing symptoms, and anxiety, which may be a latent variable reflecting executive functioning and emotion regulation skills.展开更多
BACKGROUND Resection of deep intracranial tumors requires significant brain retraction,which frequently causes brain damage.In particular,tumor in the trigone of the lateral ventricular presents a surgical challenge d...BACKGROUND Resection of deep intracranial tumors requires significant brain retraction,which frequently causes brain damage.In particular,tumor in the trigone of the lateral ventricular presents a surgical challenge due to its inaccessible location and intricate adjacent relationships with essential structures such as the optic radiation(OR)fibers.New brain retraction systems have been developed to minimize retraction-associated injury.To date,there is little evidence supporting the superiority of any retraction system in preserving the white matter tract integrity.This report illustrates the initial surgical excision in two patients using a new retraction system termed the cerebral corridor creator(CCC)and demonstrates its advantage in protecting OR fibers.CASE SUMMARY We report two patients with nonspecific symptoms,who had trigone ventricular lesions that involved the neighboring OR identified on preoperative diffusion tensor imaging(DTI).Both patients underwent successful surgical excision using the CCC.Total tumor removal was achieved without additional neurological deficit.DTI showed that the OR fibers were preserved along the surgical field.Preoperative symptoms were alleviated immediately after surgery.Clinical outcomes were improved according to the Glasgow-Outcome-Scale and Activity-of-Daily-Living Scale assessments.CONCLUSION In the two cases,the CCC was a safe and useful tool for creating access to the deep trigonal area while preserving the white matter tract integrity.The CCC is thus a promising alternative brain retractor.展开更多
Objective:lobectomy is an effective therapy for patients with Sturge-Weber syndrome(SWS).Perioperative complications often play a critical role for SWS patients’rehabilitation.This study aimed to explore and the fact...Objective:lobectomy is an effective therapy for patients with Sturge-Weber syndrome(SWS).Perioperative complications often play a critical role for SWS patients’rehabilitation.This study aimed to explore and the factors of perioperative complications in SWS patients.Methods:we reviewed retrospectively the clinical profile of totally 60 SWS patients who received surgically treatments in Sanbo Brain Hospital,Capital Medical University,from March 2009 to April 2018.Univariate analyses were used to identify the potential predictors of perioperative complications.Results:the average hospitalization time of 60 patients was(35.57±10.79)d.After surgery,54(90.00%)patients reached Engle I level.The most common postoperative complications were fever(83.33%),motor function damage(38.33%)and hyponatremia(55.00%).Univariate analyses revealed that mental retardation,seizure types and surgery types could be the predictive factors for postoperative complications.Conclusion:postoperative complications are common in SWS patients.Prediction of the severity can help doctors know what kind of special care SWS patients need to help them for further rehabilitation.展开更多
Epilepsy,a chronic neurological disorder,is characterized by dysfunction in neural networks.Gap junctions and hemichannels,which are integral to the astrocyte connection network,play a critical role in epilepsy.Connex...Epilepsy,a chronic neurological disorder,is characterized by dysfunction in neural networks.Gap junctions and hemichannels,which are integral to the astrocyte connection network,play a critical role in epilepsy.Connexins,the components of astrocyte gap junctions and hemichannels,can be activated to transfer glutamate,adenosine triphosphate,and other chemicals,potentially leading to seizures.Connexins therefore hold signifcant potential for epilepsy treatment.This review focuses on connexin 43 and provides a brief overview of other connexins and pannexin 1.Understanding the relationship between connexins and epilepsy ofers theoretical support for developing new antiseizure medications.展开更多
Background At present,a number of indicators have been analyzed for the relationship with the efficacy of vagus nerve stimulation(VNS)in drug-resistant epilepsy(DRE)patients,but there is still no definite predictor of...Background At present,a number of indicators have been analyzed for the relationship with the efficacy of vagus nerve stimulation(VNS)in drug-resistant epilepsy(DRE)patients,but there is still no definite predictor of efficacy.This study is to assess the long-term effectiveness and predictors of VNS in DRE patients.Methods We analyzed DRE patients monitored for over a year post-surgery(2016–2019)to evaluate VNS outcomes.Logistic regression was used to identify efficacy predictors.Results Out of 162 DRE patients with VNS,99 were followed for over 12 months,80 for over 24 months,and 70 for over 36 months.At 12 months,33(33.4%)showed effectiveness,including 7(7.1%)who were seizure-free.At 24 months,32(40.0%)were effective,including 12(15.0%)who were seizure-free.At 36 months,36(51.4%)were effective,including 11(15.7%)who were seizure-free.After 5 years,27(55.1%)were effective,including 8(16.3%)who were seizure-free.Multivariate regression analysis identified structural etiology as a predictive factor for the effective VNS treatment(P=0.039,OR=0.35[0.13–0.95]).Conclusions VNS effectively controls seizures,with effectiveness and seizure-free rates improving over time.Patients with structural factors are at higher risk of ineffective VNS,suggesting epilepsy etiology may predict VNS outcomes.展开更多
Deep brain stimulation(DBS)is a neurosurgical procedure that allows targeted circuit-based neuromodulation;it is also a standard of care for Parkinson’s disease(PD).[1]Postoperative DBS programming is a crucial step ...Deep brain stimulation(DBS)is a neurosurgical procedure that allows targeted circuit-based neuromodulation;it is also a standard of care for Parkinson’s disease(PD).[1]Postoperative DBS programming is a crucial step that can specify the best stimulation parameters and release symptoms to promote patients’quality of life.The“Chinese Expert Consensus on Programming Deep Brain Stimulation for Patients with Parkinson’s Disease”,which was published in 2016,regulated the application of postoperative programming for PD patients.[2]However,multiple aspects limited patients’ability to attend face-to-face programming,including their mobility and the geological distance between their residences and the DBS center,which led to a higher rate of patients using remote programming with increasing frequency,making it an urgent demand.[3,4]Therefore,it is important to create a standard protocol to guide the application of this remote treatment.展开更多
BACKGROUND： Previous studies have shown that lesions in the anterior limb of the internal capsule contribute to obsessive-compulsive symptoms in patients with refractory obsessive-compulsive disorder （OCD）. However...BACKGROUND： Previous studies have shown that lesions in the anterior limb of the internal capsule contribute to obsessive-compulsive symptoms in patients with refractory obsessive-compulsive disorder （OCD）. However, few reports have addressed the effects of lesions in the anterior limb of the internal capsule on cognition, learning, and memory functions in patients with refractory OCD. OBJECTIVE： To investigate the degree of damage to memory tasks in refractory OCD patients following lesions to the anterior limb of the internal capsule. DESIGN, TIME AND SETTING： A case-controlled, observational study was performed at the Department of Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao-Tong University, China from May 2007 to March 2008. PARTICIPANTS： A total of 10 refractory OCD patients were admitted to the Department of Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao-Tong University, China from May 2007 to March 2008 and were recruited for this study. The OCD patients were of equal gender, with an average age of （25.1 ± 9.6） years. An additional 10 healthy volunteers were enrolled from a community of Shanghai City as controls; they were of equal gender and aged （25.1 ± 8.6） years. METHODS： A total of 10 refractory OCD patients were subjected to lesions in the anterior limbs of the bilateral internal capsules. Wechsler Memory Scale-Chinese Revision （WMS-CR, as a task of explicit memory） and the Nissen Version （serial reaction time task） software （SRTT, as a task of implicit memory） were applied to determine memory functions and learning performance in pre- and post-operative OCD patients and controls. MAIN OUTCOME MEASURES： WMS scores, reaction time in SRTT, and Yale-Brown obsessive compulsive scale scores were measured in pre- and post-operative OCD patients and controls. RESULTS： Compared to controls, the pre-operative OCD patients exhibited reduced memory task scores （P = 0.005）, whereas scores for reciting numbers of backwards digits were greater （P = 0.000）. Figure recall and associative memory were less in OCD patients at 1 week following surgery than in the pre-operative OCD patients （P = 0.042, P = 0.002, respectively）. Reaction time in implicit SRTT was significantly longer in pre-operative OCD patients compared with controls and post-operative OCD patients （P = 0.01, P = 0.03, respectively）. These results suggested ameliorated SRTT following neurosurgery. Yale-Brown Obsessive Compulsive Scale results revealed significantly improved OCD following lesions in the internal capsule （P = 0.04）. Some post-operative OCD patients suffered from deficits in short-term memory and implicit memory. CONCLUSION： Lesions in anterior limbs of bilateral internal capsules improve obsessive- compulsive symptoms and implicit memory in OCD patients, but result in aggravated short-term memory deficits.展开更多
Neuropeptide Y has been shown to inhibit the immunological activity of reactive microglia in the rat cerebral cortex, to reduce N-methyl-D-aspartate current（INMDA） in cortical neurons, and protect neurons. In this s...Neuropeptide Y has been shown to inhibit the immunological activity of reactive microglia in the rat cerebral cortex, to reduce N-methyl-D-aspartate current（INMDA） in cortical neurons, and protect neurons. In this study, after primary cultured microglia from the cerebral cortex of rats were treated with lipopolysaccharide, interleukin-1β and tumor necrosis factor-α levels in the cell culture medium increased, and mRNA expression of these cytokines also increased. After primary cultured cortical neurons were incubated with the lipopolysaccharide-treated microglial conditioned medium, peak INMDA in neurons increased. These effects of lipopolysaccharide were suppressed by neuropeptide Y. After addition of the neuropeptide Y Y1 receptor antagonist BIBP3226, the effects of neuropeptide Y completely disappeared. These results suggest that neuropeptide Y prevents excessive production of interleukin-1β and tumor necrosis factor-α by inhibiting microglial reactivity. This reduces INMDA in rat cortical neurons, preventing excitotoxicity, thereby protecting neurons.展开更多
Objective To investigate the frequency of GAG deletion in the DYT1 gene among early onset primary dystonia patients in China. Methods Thirteen patients with early onset primary torsion dystonia were screened for muta...Objective To investigate the frequency of GAG deletion in the DYT1 gene among early onset primary dystonia patients in China. Methods Thirteen patients with early onset primary torsion dystonia were screened for mutation in exon 5 of the DYT1 gene using denaturing high-performance liquid chromatography （DHPLC） and DNA sequencing, and the results were confirmed with polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Results The GAG deletion mutation which results in Glu302del in exon 5 of the DYT1 gene was found in 5 patients. The detecting results were consistent between with DHPLC and PCR-RFLP. We did not find any other mutations in the DYT1 gene. Conel^iotm The GAG deletion in the DYT1 gene is common amongst early onset primary torsion dystonia patients in Chin＆ The frequency of DYT1 mutation is not significantly different between European and Asian patients with early onset primary dystonia.展开更多
Cognitive dysfunction stands as a prevalent and consequential non-motor manifestation in Parkinson's disease(PD).Although dysfunction of the olfactory system has been recognized as an important predictor of cognit...Cognitive dysfunction stands as a prevalent and consequential non-motor manifestation in Parkinson's disease(PD).Although dysfunction of the olfactory system has been recognized as an important predictor of cognitive decline,the exact mechanism by which aberrant olfactory circuits contribute to cognitive dysfunction in PD is unclear.Here,we provide the first evidence for abnormal functional connectivity across olfactory bulb(OB)and piriform cortex(PC)or entorhinal cortex(EC)by clinical fMRl,and dysfunction of neural coherence in the olfactory system in PD mice.Moreover,we discovered that 2 subpopulations of mitral/tufted(M/T)cells in OB projecting to anterior PC(aPC)and EC precisely mediated the process of cognitive memory respectively by neural coherence at specific frequencies in mice.In addition,the transcriptomic profiling analysis and functional genetic regulation analysis further revealed that biorientation defective 1(Bodl)may play a pivotal role in encoding OB^(M/T)-mediated cognitive function.We also verified that a new deep brain stimulation protocol in OB ameliorated the cognitive function of Bodl-deficient mice and PD mice.Together,aberrant coherent activity in the olfactory system can serve as a biomarker for assessing cognitive function and provide a candidate therapeutic target for the treatment of PD.展开更多
To review the literature on the use of brain imaging, including functional magnetic resonance imaging （fMRI）, positron emission tomography （PET）, magnetic resonance spectroscopy （MRS） and voxel-based morphometry...To review the literature on the use of brain imaging, including functional magnetic resonance imaging （fMRI）, positron emission tomography （PET）, magnetic resonance spectroscopy （MRS） and voxel-based morphometry （VBM） in investigation of the activity in diverse brain regions that creates and modulates chronic neuropathic pain. Data sources English literatures from January 1, 2000 to July 31, 2007 that examined human brain activity in chronic neuropathic pain were accessed through MEDLINE/CD ROM, using PET, fMRI, VBM, MRS and receptor binding. Study selection Published articles about the application of fMRI, PET, VBM, MRS and chronic neuropathic pain were selected. Data extraction Data were mainly extracted from 40 representative articles as the research basis. Results The PET studies suggested that spontaneous neuropathic pain is associated with changes in thalamic activity. Both PET and fMRI have been used to investigate the substrate of allodynia. The VBM demonstrated that brain structural changes are involved in chronic neuropathic pain, which is not seen in a matched control group. However, the results obtained had a large variety, which may be due to different pain etiology, pain distribution, lesion tomography, symptoms and stimulation procedures. Conclusions Application of the techniques of brain imaging plays a very important role in the study of structural and functional reorganization in patients with neuropathic pain. However, a unique “pain matrix” has not been defined. Future studies should be conducted using a prospective longitudinal research design, which would guarantee the control for many confounding factors.展开更多
Background Vagus nerve stimulation （VNS） is an alternative treatment for drug-resistant epilepsy （DRE）. The study aimed to explore the potential factors of prognosis, safety and effect of VNS treatment in patients...Background Vagus nerve stimulation （VNS） is an alternative treatment for drug-resistant epilepsy （DRE）. The study aimed to explore the potential factors of prognosis, safety and effect of VNS treatment in patients with DRE. Methods We retrospectively examined 45 cases of DRE that received VNS treatment in our center from June 2004 to June 2010 and analyzed the parameters （age of patient receiving VNS, seizure frequency before and after VNS as well as treatment duration） by Student＇s t test, Fisher＇s exact and Mann-Whitney U tests, and multivariate Logistic regression. Results The overall response rate was 64% （29/45）, 67% （6/9） for adults and 64% （23/36） for children, with no significant difference （P=0.28）. Twenty-two cases had been in VNS therapy for over 1 year with a treatment efficacy of 73% （16/22）, whereas 23 cases had been in VNS therapy no more than 1 year with a treatment effecacy of 57% （13/23）, and has statistically significant difference （P=0.03）. The main side effect included hoarseness of voice and cough. One patient＇s device was removed due to infection. One patient＇s VNS was half-way terminated due to seizure aggravation. One patient died due to status epilepticus. Conclusions VNS is a safe and effective treatment for DRE. Duration of VNS therapy may be a crucial factor on prognosis.展开更多
Background：The antiepileptic effect of the anterior thalamic nuclei （ANT） stimulation has been demonstrated;however,its underlying mechanism remains unclear.The aim of this study was to investigate the effect of ch...Background：The antiepileptic effect of the anterior thalamic nuclei （ANT） stimulation has been demonstrated;however,its underlying mechanism remains unclear.The aim of this study was to investigate the effect of chronic ANT stimulation on hippocampal neuron loss and apoptosis.Methods：Sixty-four rats were divided into four groups：The control group,the kainic acid （KA） group,the sham-deep brain stimulation （DBS） group,and the DBS group.KA was used to induce epilepsy.Seizure count and latency to the first spontaneous seizures were calculated.Nissl staining was used to analyze hippocampal neuronal loss.Polymerase chain reaction and Western blotting were conducted to assess the expression of caspase-3 （Casp3）,B-cell lymphoma-2 （Bcl2）,and Bcl2-associated X protein （Box） in the hippocampal CA3 region.One-way analysis of variance was used to determine the differences between the four groups.Results：The latency to the first spontaneous seizures in the DBS group was significantly longer than that in the KA group （27.50 ± 8.05 vs.16.38 ± 7.25 days,P =0.0005）.The total seizure number in the DBS group was also significantly reduced （DBS vs.KA group：11.75 ± 6.80 vs.23.25 ± 7.72,P =0.0002）.Chronic ANT-DBS reduced neuronal loss in the hippocampal CA3 region （DBS vs.KA group：23.58 ± 6.34 vs.13.13 ± 4.00,P =0.0012）.After chronic DBS,the relative mRNA expression level of Casp3 was decreased （DBS vs.KA group：1.18 ± 0.37 vs.2.09 ± 0.46,P =0.0003）,and the relative mRNA expression level of Bcl2 was increased （DBS vs.KA group：0.92 ± 0.21 vs.0.48 ± 0.16,P =0.0004）.The protein expression levels of CASP3 （DBS vs.KA group：1.25 ± 0.26 vs.2.49 ± 0.38,P 〈 0.0001） and BAX （DBS vs.KA group：1.57 ± 0.49 vs.2.80 ± 0.63,P =0.0012） both declined in the DBS group whereas the protein expression level of BCL2 （DBS vs.KA group：0.78 ± 0.32 vs.0.36 ± 0.17,P =0.0086） increased in the DBS group.Conclusions：This study demonstrated that chronic ANT stimulation could exert a neuroprotective effect on hippocampal neurons.This neuroprotective effect is likely to be mediated by the inhibition of apoptosis in the epileptic hippocampus.展开更多
基金supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB02050006)the National Natural Science Foundation of China (81571300, 81527901, 31771174, 81271518 and 81471387)+4 种基金the National Key R&D Program of China (2017YFC1310400)the Natural Science Foundation and Major Basic Research Program of Shanghai (16JC1420100)the support from Shanghai JiaoTong University School of Medicine Institute of Neuroscience Research Center for Brain Disordersthe Shanghai JiaoTong University K.C. Wong Medical Fellowship Fundfunded by the Michael J. Fox Foundation for Parkinson’s Research
文摘Neurostimulation remarkably alleviates the symptoms in a variety of brain disorders by modulating the brain-wide network. However, how brain-wide effects on the direct and indirect pathways evoked by focal neurostimulation elicit therapeutic effects in an individual patient is unknown. Understanding this remains crucial for advancing neural circuit-based guidance to optimize candidate patient screening, pre-surgical target selection, and post-surgical parameter tuning. To address this issue, we propose a functional brain connectome-based modeling approach that simulates the spreading effects of stimulating different brain regions and quantifies the rectification of abnormal network topology in silico. We validated these analyses by pinpointing nuclei in the basal ganglia circuits as top-ranked targets for 43 local patients with Parkinson’s disease and 90 patients from a public database. Individual connectome-based analysis demonstrated that the globus pallidus was the best choice for 21.1% and the subthalamic nucleus for 19.5% of patients. Down-regulation of functional connectivity(up to 12%) at these prioritized targets optimally maximized the therapeutic effects. Notably, the priority rank of the subthalamic nucleus significantly correlated with motor symptom severity(Unified Parkinson’s Disease Rating Scale III) in the local cohort. These findings underscore the potential of neural network modeling for advancing personalized brain stimulation therapy,and warrant future experimental investigation to validate its clinical utility.
基金supported by National Natural Science Foundation of China(81071065)
文摘Deep brain stimulation （DBS） is an effective technique for treating Parkinson＇s disease （PD） in the middle and advanced stages. The subthalamic nucleus （STN） is the most common target for clinical treatment using DBS. While STN-DBS can significantly improve motor symptoms in PD patients, adverse cognitive effects have also been reported. The specific effects of STN-DBS on cognitive function and the related mechanisms remain unclear. Thus, it is imperative to identify the influence of STN-DBS on cognition and investigate the potential mechanisms to provide a clearer view of the various cognitive sequelae in PD patients. For this review, a literature search was performed using the following inclusion criteria： （1） at least 10 patients followed for a mean of at least 6 months after surgery since the year 2006; （2） pre- and postoperative cognitive data using at least one standardized neuropsychological scale; and （3） adequate reporting of study results using means and standard deviations. Of -170 clinical studies identified, 25 cohort studies （including 15 self-controlled studies, nine intergroup controlled studies, and one multi-center, randomized control experiment） and one meta- analysis were eligible for inclusion. The results suggest that the precise mechanism of the changes in cognitive function after STN-DBS remains obscure, but STN-DBS certainly has effects on cognition. In particular, a progressive decrease in verbal fluency after STN-DBS is consistently reported and although executive function is unchanged in the intermediate stage postoperatively, it tends to decline in the early and later stages. However, these changes do not affect the improvements in quality of life. STN-DBS seems to be safe with respect to cognitive effects in carefully-selected patients during a follow-up period from 6 months to 9 years.
基金support by the National Nature Science Foundation of China,Nos.81830033,61761166004(both to JGZ)。
文摘There are many documented sex differences in the clinical course,symptom expression profile,and treatment response of Parkinson’s disease,creating additional challenges for patient management.Although subthalamic nucleus deep brain stimulation is an established therapy for Parkinson’s disease,the effects of sex on treatment outcome are still unclear.The aim of this retrospective observational study,was to examine sex differences in motor symptoms,nonmotor symptoms,and quality of life after subthalamic nucleus deep brain stimulation.Outcome measures were evaluated at 1 and 12 months post-operation in 90 patients with Parkinson’s disease undergoing subthalamic nucleus deep brain stimulation aged 63.00±8.01 years(55 men and 35 women).Outcomes of clinical evaluations were compared between sexes via a Student’s t-test and within sex via a paired-sample t-test,and generalized linear models were established to identify factors associated with treatment efficacy and intensity for each sex.We found that subthalamic nucleus deep brain stimulation could improve motor symptoms in men but not women in the on-medication condition at 1 and 12 months post-operation.Restless legs syndrome was alleviated to a greater extent in men than in women.Women demonstrated poorer quality of life at baseline and achieved less improvement of quality of life than men after subthalamic nucleus deep brain stimulation.Furthermore,Hoehn-Yahr stage was positively correlated with the treatment response in men,while levodopa equivalent dose at 12 months post-operation was negatively correlated with motor improvement in women.In conclusion,women received less benefit from subthalamic nucleus deep brain stimulation than men in terms of motor symptoms,non-motor symptoms,and quality of life.We found sex-specific factors,i.e.,Hoehn-Yahr stage and levodopa equivalent dose,that were related to motor improvements.These findings may help to guide subthalamic nucleus deep brain stimulation patient selection,prognosis,and stimulation programming for optimal therapeutic efficacy in Parkinson’s disease.
文摘Neuropeptide Y gene transfection into normal rat brain tissue can provide gene overexpression, which can attenuate the severity of kainic acid-induced seizures. In this study, a recombinant adeno-associated virus carrying the neuropeptide Y gene was transfected into brain tissue of rats with kainic acid-induced epilepsy through stereotactic methods. Following these transfections, we verified overexpression of the neuropeptide Y gene in the epileptic brain. Electroencephalograms showed that seizure severity was significantly inhibited and seizure latency was significantly prolonged up to 4 weeks after gene transfection. Moreover, quantitative fluorescent PCR and western blot assays revealed that the mRNA and protein expression of the N-methyI-D-aspartate receptor subunits NR1, NR2A, and NR2B was inhibited in the hippocampus of epileptic rats. These findings indicate that neuropeptide Y may inhibit seizures via down-regulation of the functional expression of N-methyI-D-aspartate receptors.
基金supported by the National Natural Science Foundation of China,No.81201984the Scientific Research Project of Shaanxi Provincial Health Department in China,No.2010E03the Yulin Municipal Science and Technology Research and Development Project,No.Sf12-06
文摘The activity of the Schaffer collaterals of hippocampal CA3 neurons and hippocampal CA1 neurons has been shown to increase after lfuid percussion injury. Diazepam can inhibit the hy-perexcitability of rat hippocampal neurons after injury, but the mechanism by which it affects excitatory synaptic transmission remains poorly understood. Our results showed that diazepam treatment signiifcantly increased the slope of input-output curves in rat neurons after lfuid per-cussion injury. Diazepam signiifcantly decreased the numbers of spikes evoked by super stimuli in the presence of 15 μmol/L bicuculline, indicating the existence of inhibitory pathways in the injured rat hippocampus. Diazepam effectively increased the paired-pulse facilitation ratio in the hippocampal CA1 region following fluid percussion injury, reduced miniature excitatory postsynaptic potentials, decreased action-potential-dependent glutamine release, and reversed spontaneous glutamine release. These data suggest that diazepam could decrease the lfuid per-cussion injury-induced enhancement of excitatory synaptic transmission in the rat hippocampal CA1 area.
文摘BACKGROUND Implant vagus nerve stimulation is an adjunctive treatment for intractable epilepsy when patients are not suitable for resective surgery.AIM To identify the safety and efficacy of vagus nerve stimulation in children with intractable epilepsy and analyze the effects on different epilepsy syndromes.METHODS Eligible children with intractable epilepsy were admitted to the study.We collected data from preoperative assessments as the baseline.During the followup time,we recorded the process of seizures(frequency,duration,and seizure type),the changes of drugs or parameters,the complications,etc.The mean reduction rate of seizures,response rate,and McHugh scale were chosen as the outcomes.RESULTS A total of 213 patients were implanted with Tsinghua Pins vagus nerve stimulators,and the average age was 6.6 years.In the follow-up time of postoperative 3 mo,6 mo,12 mo,18 mo,and 24 mo,the average reduction rate was 30.2%,49.5%,56.3%,59.4%,and 63.2%,while the response rate was 21.8%,62.5%,57.1%,69.2%,and 70.7%.In addition,implanted vagus nerve stimulation had different effects on epilepsy syndromes.The reduction rate of West syndrome increased from 36.4%(postoperative 6 m)to 74.3%(postoperative 24 m).The reduction rate of Lennox-Gastaut syndrome improved from 25.4%to 73.1%in 24 mo.The chi-square test of the five efficacy grades showed P<0.05.The comparison between the 3-mo follow-up and the 6-mo follow-up showed P<0.05,and the comparison between the 6-mo follow-up and the 24-mo follow-up showed P>0.05.CONCLUSION Vagus nerve stimulation is safe and effective in children with intractable epilepsy,and the seizure reduction occurred in a time-dependent manner.Moreover,patients with West syndrome may get the most benefits.
基金Postdoctoral Science Foundation of China, No. 20070420399
文摘BACKGROUND： Deep-brain stimulation has proven to be beneficial in the treatment of Parkinson＇s disease （PD） patients. OBJECTIVE： To investigate the effects of high-frequency stimulation （HFS） to the subthalamic nucleus （STN） on neuronal apoptosis and apoptosis-related gene expression in the substantia nigra pars compacta, and to analyze the neuroprotective effect of HFS-STN. DESIGN, TIME AND SETTING： Neuronal morphology experiments were performed in the Beijing Neurosurgical Institute from May to December in 2005. MATERIALS： Forty healthy, adult, Sprague Dawley rats were used to establish a PD model with a unilateral microinjection of 6-hydroxydopamine into two target areas of the right medial forebrain bundle. 6-hydroxydopamine was purchased from Sigma （USA）; high-frequency electrical stimulator was produced by World Precision Instruments （USA）; Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） kit was a product of Nanjing Jiancheng Technology Co., Ltd. （China）; and Bcl-2 and Bax protein assay kit were purchased from Wuhan Boster Bioengineering Co., Ltd. （China）. METHODS： Forty rats were randomly divided into three groups. The stimulation group （n = 15） received HFS-STN on the day of PD modeling. The PD model group （n = 15） was used to establish the PD model. The control group （n = 10） was injected with normal saline containing 0.2 g/L ascorbic acid into two areas of the right medial forebrain bundle. MAIN OUTCOME MEASURES： Survival of dopaminergic neurons in the substantia nigra pars compacta was determined using Nissl staining. Apoptosis of dopaminergic neurons was detected using TUNEL techniques. Expression of anti-apoptotic protein, Bcl-2, and pro-apoptotic protein, Bax, were assayed by immunohistochemistry. RESULTS： Following 6-hydroxydopamine injection, the number of substantia nigra pars compacta neurons was reduced in the stimulation and PD model groups, compared to the control group. At 2 and 4 weeks post-surgery, the grey value of Nissl stained images was significantly less in the PD model and stimulation groups （P 〈 0.05）, and the stimulation group exhibited greater grey values compared to the model group （P 〈 0.05）. At 2 and 4 weeks post-surgery, the number of apoptotic neurons was significantly less in the stimulation group compared to the model group （P 〈 0.05）. In addition, Bcl-2 and Bax expression, as well as the Bcl-2/Bax ratio, was much higher in the stimulation group compared to the model group （P 〈 0.05）. CONCLUSION： HFS-STN has a neuroprotective effect on dopaminergic neurons in the substantia nigra pars compacta of PD rats by promoting Bcl-2 expression, inhibiting Bax expression, and reducing the number of apoptotic dopaminergic neurons.
基金Project supported by the Shanghai Pudong New District Health and Family Planning Commission Key Discipline Construction Fund Project(No.PWZxk2017-29),China
文摘Objective: Anger attacks have been observed in patients with obsessive-compulsive disorder(OCD), often triggered by obsessional triggers. However, few studies have reported the clinical characteristics and correlates of anger attacks among Chinese patients with OCD. Methods: A total of 90 adults with a primary diagnosis of OCD, ranging from 15 to 78 years old, participated in the study. Participants were administered the Rage Outbursts and Anger Rating Scale(ROARS), Yale-Brown Obsessive-Compulsive Scale-Second Edition, and Brown Assessment of Beliefs Scale by a trained clinician. Patients completed the Obsessive-Compulsive Inventory-Revised and Depression Anxiety Stress Scale-21. Results: A total of 31.3% of participants reported anger outbursts in the past week, and ROARS scores had no significant correlation with age, duration of illness, OCD severity, depression, or stress. However, ROARS scores were negatively related to education level, and positively related to obsessing symptoms and anxiety. Conclusions: These data suggest that anger attacks are relatively common in Chinese patients with OCD. The severity of anger attacks is related to educational level, obsessing symptoms, and anxiety, which may be a latent variable reflecting executive functioning and emotion regulation skills.
文摘BACKGROUND Resection of deep intracranial tumors requires significant brain retraction,which frequently causes brain damage.In particular,tumor in the trigone of the lateral ventricular presents a surgical challenge due to its inaccessible location and intricate adjacent relationships with essential structures such as the optic radiation(OR)fibers.New brain retraction systems have been developed to minimize retraction-associated injury.To date,there is little evidence supporting the superiority of any retraction system in preserving the white matter tract integrity.This report illustrates the initial surgical excision in two patients using a new retraction system termed the cerebral corridor creator(CCC)and demonstrates its advantage in protecting OR fibers.CASE SUMMARY We report two patients with nonspecific symptoms,who had trigone ventricular lesions that involved the neighboring OR identified on preoperative diffusion tensor imaging(DTI).Both patients underwent successful surgical excision using the CCC.Total tumor removal was achieved without additional neurological deficit.DTI showed that the OR fibers were preserved along the surgical field.Preoperative symptoms were alleviated immediately after surgery.Clinical outcomes were improved according to the Glasgow-Outcome-Scale and Activity-of-Daily-Living Scale assessments.CONCLUSION In the two cases,the CCC was a safe and useful tool for creating access to the deep trigonal area while preserving the white matter tract integrity.The CCC is thus a promising alternative brain retractor.
文摘Objective:lobectomy is an effective therapy for patients with Sturge-Weber syndrome(SWS).Perioperative complications often play a critical role for SWS patients’rehabilitation.This study aimed to explore and the factors of perioperative complications in SWS patients.Methods:we reviewed retrospectively the clinical profile of totally 60 SWS patients who received surgically treatments in Sanbo Brain Hospital,Capital Medical University,from March 2009 to April 2018.Univariate analyses were used to identify the potential predictors of perioperative complications.Results:the average hospitalization time of 60 patients was(35.57±10.79)d.After surgery,54(90.00%)patients reached Engle I level.The most common postoperative complications were fever(83.33%),motor function damage(38.33%)and hyponatremia(55.00%).Univariate analyses revealed that mental retardation,seizure types and surgery types could be the predictive factors for postoperative complications.Conclusion:postoperative complications are common in SWS patients.Prediction of the severity can help doctors know what kind of special care SWS patients need to help them for further rehabilitation.
基金supported by Natural Science Foundation of Beijing Municipality(grant number L222078)National Science Foundation of China(grant number 82071448)。
文摘Epilepsy,a chronic neurological disorder,is characterized by dysfunction in neural networks.Gap junctions and hemichannels,which are integral to the astrocyte connection network,play a critical role in epilepsy.Connexins,the components of astrocyte gap junctions and hemichannels,can be activated to transfer glutamate,adenosine triphosphate,and other chemicals,potentially leading to seizures.Connexins therefore hold signifcant potential for epilepsy treatment.This review focuses on connexin 43 and provides a brief overview of other connexins and pannexin 1.Understanding the relationship between connexins and epilepsy ofers theoretical support for developing new antiseizure medications.
基金supported by the project of National Key R&D Program of China(2021YFC2401201).
文摘Background At present,a number of indicators have been analyzed for the relationship with the efficacy of vagus nerve stimulation(VNS)in drug-resistant epilepsy(DRE)patients,but there is still no definite predictor of efficacy.This study is to assess the long-term effectiveness and predictors of VNS in DRE patients.Methods We analyzed DRE patients monitored for over a year post-surgery(2016–2019)to evaluate VNS outcomes.Logistic regression was used to identify efficacy predictors.Results Out of 162 DRE patients with VNS,99 were followed for over 12 months,80 for over 24 months,and 70 for over 36 months.At 12 months,33(33.4%)showed effectiveness,including 7(7.1%)who were seizure-free.At 24 months,32(40.0%)were effective,including 12(15.0%)who were seizure-free.At 36 months,36(51.4%)were effective,including 11(15.7%)who were seizure-free.After 5 years,27(55.1%)were effective,including 8(16.3%)who were seizure-free.Multivariate regression analysis identified structural etiology as a predictive factor for the effective VNS treatment(P=0.039,OR=0.35[0.13–0.95]).Conclusions VNS effectively controls seizures,with effectiveness and seizure-free rates improving over time.Patients with structural factors are at higher risk of ineffective VNS,suggesting epilepsy etiology may predict VNS outcomes.
基金National Key Research and Development Program of China(Nos.2022YFC2405100 and 2021YFC2401200)National Natural Science Foundation of China(No.81830033)+1 种基金Key R&D Program of Jiangsu Science and Technology Project(No.BE2022049)Key Research and Development Program of Henan Province(No.241111310100)
文摘Deep brain stimulation(DBS)is a neurosurgical procedure that allows targeted circuit-based neuromodulation;it is also a standard of care for Parkinson’s disease(PD).[1]Postoperative DBS programming is a crucial step that can specify the best stimulation parameters and release symptoms to promote patients’quality of life.The“Chinese Expert Consensus on Programming Deep Brain Stimulation for Patients with Parkinson’s Disease”,which was published in 2016,regulated the application of postoperative programming for PD patients.[2]However,multiple aspects limited patients’ability to attend face-to-face programming,including their mobility and the geological distance between their residences and the DBS center,which led to a higher rate of patients using remote programming with increasing frequency,making it an urgent demand.[3,4]Therefore,it is important to create a standard protocol to guide the application of this remote treatment.
基金the Key Program of International Communication Foundation of Psychiatry and Neurology Department of Shanghai Jiao-Tong University, No. 200901
文摘BACKGROUND： Previous studies have shown that lesions in the anterior limb of the internal capsule contribute to obsessive-compulsive symptoms in patients with refractory obsessive-compulsive disorder （OCD）. However, few reports have addressed the effects of lesions in the anterior limb of the internal capsule on cognition, learning, and memory functions in patients with refractory OCD. OBJECTIVE： To investigate the degree of damage to memory tasks in refractory OCD patients following lesions to the anterior limb of the internal capsule. DESIGN, TIME AND SETTING： A case-controlled, observational study was performed at the Department of Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao-Tong University, China from May 2007 to March 2008. PARTICIPANTS： A total of 10 refractory OCD patients were admitted to the Department of Functional Neurosurgery, Ruijin Hospital, Shanghai Jiao-Tong University, China from May 2007 to March 2008 and were recruited for this study. The OCD patients were of equal gender, with an average age of （25.1 ± 9.6） years. An additional 10 healthy volunteers were enrolled from a community of Shanghai City as controls; they were of equal gender and aged （25.1 ± 8.6） years. METHODS： A total of 10 refractory OCD patients were subjected to lesions in the anterior limbs of the bilateral internal capsules. Wechsler Memory Scale-Chinese Revision （WMS-CR, as a task of explicit memory） and the Nissen Version （serial reaction time task） software （SRTT, as a task of implicit memory） were applied to determine memory functions and learning performance in pre- and post-operative OCD patients and controls. MAIN OUTCOME MEASURES： WMS scores, reaction time in SRTT, and Yale-Brown obsessive compulsive scale scores were measured in pre- and post-operative OCD patients and controls. RESULTS： Compared to controls, the pre-operative OCD patients exhibited reduced memory task scores （P = 0.005）, whereas scores for reciting numbers of backwards digits were greater （P = 0.000）. Figure recall and associative memory were less in OCD patients at 1 week following surgery than in the pre-operative OCD patients （P = 0.042, P = 0.002, respectively）. Reaction time in implicit SRTT was significantly longer in pre-operative OCD patients compared with controls and post-operative OCD patients （P = 0.01, P = 0.03, respectively）. These results suggested ameliorated SRTT following neurosurgery. Yale-Brown Obsessive Compulsive Scale results revealed significantly improved OCD following lesions in the internal capsule （P = 0.04）. Some post-operative OCD patients suffered from deficits in short-term memory and implicit memory. CONCLUSION： Lesions in anterior limbs of bilateral internal capsules improve obsessive- compulsive symptoms and implicit memory in OCD patients, but result in aggravated short-term memory deficits.
文摘Neuropeptide Y has been shown to inhibit the immunological activity of reactive microglia in the rat cerebral cortex, to reduce N-methyl-D-aspartate current（INMDA） in cortical neurons, and protect neurons. In this study, after primary cultured microglia from the cerebral cortex of rats were treated with lipopolysaccharide, interleukin-1β and tumor necrosis factor-α levels in the cell culture medium increased, and mRNA expression of these cytokines also increased. After primary cultured cortical neurons were incubated with the lipopolysaccharide-treated microglial conditioned medium, peak INMDA in neurons increased. These effects of lipopolysaccharide were suppressed by neuropeptide Y. After addition of the neuropeptide Y Y1 receptor antagonist BIBP3226, the effects of neuropeptide Y completely disappeared. These results suggest that neuropeptide Y prevents excessive production of interleukin-1β and tumor necrosis factor-α by inhibiting microglial reactivity. This reduces INMDA in rat cortical neurons, preventing excitotoxicity, thereby protecting neurons.
基金Supported by grants from Ministry of Sciences and Technology of China(2006CB500701,2002BA711A10)National Natural Science Foundation of China(30430280)+1 种基金Beijing Municipal Commission on Sciences and Technology(H020220020610,7031002)Beijing Bureau of Health(2003-2029)
文摘Objective To investigate the frequency of GAG deletion in the DYT1 gene among early onset primary dystonia patients in China. Methods Thirteen patients with early onset primary torsion dystonia were screened for mutation in exon 5 of the DYT1 gene using denaturing high-performance liquid chromatography （DHPLC） and DNA sequencing, and the results were confirmed with polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. Results The GAG deletion mutation which results in Glu302del in exon 5 of the DYT1 gene was found in 5 patients. The detecting results were consistent between with DHPLC and PCR-RFLP. We did not find any other mutations in the DYT1 gene. Conel^iotm The GAG deletion in the DYT1 gene is common amongst early onset primary torsion dystonia patients in Chin＆ The frequency of DYT1 mutation is not significantly different between European and Asian patients with early onset primary dystonia.
基金supported by the National Key Research and Development Program of China(2022YFE0108600 to Y.-M.L.)the National Innovation of Science and Technology-2030,STI2030-Major Projects 2021ZD0204000(2021ZD0204002 to Y.-M.L.)+2 种基金the State Key Program of National Natural Science Foundations of China(81930103 to FH.)the National Natural Science Foundation of China(82404596 to X.-F.M.)the Key R&D Program of jiangsu Science and Technology Project(BE2022049 and BE2022049-1 to W.-B.Z.).
文摘Cognitive dysfunction stands as a prevalent and consequential non-motor manifestation in Parkinson's disease(PD).Although dysfunction of the olfactory system has been recognized as an important predictor of cognitive decline,the exact mechanism by which aberrant olfactory circuits contribute to cognitive dysfunction in PD is unclear.Here,we provide the first evidence for abnormal functional connectivity across olfactory bulb(OB)and piriform cortex(PC)or entorhinal cortex(EC)by clinical fMRl,and dysfunction of neural coherence in the olfactory system in PD mice.Moreover,we discovered that 2 subpopulations of mitral/tufted(M/T)cells in OB projecting to anterior PC(aPC)and EC precisely mediated the process of cognitive memory respectively by neural coherence at specific frequencies in mice.In addition,the transcriptomic profiling analysis and functional genetic regulation analysis further revealed that biorientation defective 1(Bodl)may play a pivotal role in encoding OB^(M/T)-mediated cognitive function.We also verified that a new deep brain stimulation protocol in OB ameliorated the cognitive function of Bodl-deficient mice and PD mice.Together,aberrant coherent activity in the olfactory system can serve as a biomarker for assessing cognitive function and provide a candidate therapeutic target for the treatment of PD.
基金This research was supported by a grant from the Natural Science Foundation of Beijing （No. 5082008）.
文摘To review the literature on the use of brain imaging, including functional magnetic resonance imaging （fMRI）, positron emission tomography （PET）, magnetic resonance spectroscopy （MRS） and voxel-based morphometry （VBM） in investigation of the activity in diverse brain regions that creates and modulates chronic neuropathic pain. Data sources English literatures from January 1, 2000 to July 31, 2007 that examined human brain activity in chronic neuropathic pain were accessed through MEDLINE/CD ROM, using PET, fMRI, VBM, MRS and receptor binding. Study selection Published articles about the application of fMRI, PET, VBM, MRS and chronic neuropathic pain were selected. Data extraction Data were mainly extracted from 40 representative articles as the research basis. Results The PET studies suggested that spontaneous neuropathic pain is associated with changes in thalamic activity. Both PET and fMRI have been used to investigate the substrate of allodynia. The VBM demonstrated that brain structural changes are involved in chronic neuropathic pain, which is not seen in a matched control group. However, the results obtained had a large variety, which may be due to different pain etiology, pain distribution, lesion tomography, symptoms and stimulation procedures. Conclusions Application of the techniques of brain imaging plays a very important role in the study of structural and functional reorganization in patients with neuropathic pain. However, a unique “pain matrix” has not been defined. Future studies should be conducted using a prospective longitudinal research design, which would guarantee the control for many confounding factors.
文摘Background Vagus nerve stimulation （VNS） is an alternative treatment for drug-resistant epilepsy （DRE）. The study aimed to explore the potential factors of prognosis, safety and effect of VNS treatment in patients with DRE. Methods We retrospectively examined 45 cases of DRE that received VNS treatment in our center from June 2004 to June 2010 and analyzed the parameters （age of patient receiving VNS, seizure frequency before and after VNS as well as treatment duration） by Student＇s t test, Fisher＇s exact and Mann-Whitney U tests, and multivariate Logistic regression. Results The overall response rate was 64% （29/45）, 67% （6/9） for adults and 64% （23/36） for children, with no significant difference （P=0.28）. Twenty-two cases had been in VNS therapy for over 1 year with a treatment efficacy of 73% （16/22）, whereas 23 cases had been in VNS therapy no more than 1 year with a treatment effecacy of 57% （13/23）, and has statistically significant difference （P=0.03）. The main side effect included hoarseness of voice and cough. One patient＇s device was removed due to infection. One patient＇s VNS was half-way terminated due to seizure aggravation. One patient died due to status epilepticus. Conclusions VNS is a safe and effective treatment for DRE. Duration of VNS therapy may be a crucial factor on prognosis.
基金This study was supported by grants from the National Natural Science Foundation of China，the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding
文摘Background：The antiepileptic effect of the anterior thalamic nuclei （ANT） stimulation has been demonstrated;however,its underlying mechanism remains unclear.The aim of this study was to investigate the effect of chronic ANT stimulation on hippocampal neuron loss and apoptosis.Methods：Sixty-four rats were divided into four groups：The control group,the kainic acid （KA） group,the sham-deep brain stimulation （DBS） group,and the DBS group.KA was used to induce epilepsy.Seizure count and latency to the first spontaneous seizures were calculated.Nissl staining was used to analyze hippocampal neuronal loss.Polymerase chain reaction and Western blotting were conducted to assess the expression of caspase-3 （Casp3）,B-cell lymphoma-2 （Bcl2）,and Bcl2-associated X protein （Box） in the hippocampal CA3 region.One-way analysis of variance was used to determine the differences between the four groups.Results：The latency to the first spontaneous seizures in the DBS group was significantly longer than that in the KA group （27.50 ± 8.05 vs.16.38 ± 7.25 days,P =0.0005）.The total seizure number in the DBS group was also significantly reduced （DBS vs.KA group：11.75 ± 6.80 vs.23.25 ± 7.72,P =0.0002）.Chronic ANT-DBS reduced neuronal loss in the hippocampal CA3 region （DBS vs.KA group：23.58 ± 6.34 vs.13.13 ± 4.00,P =0.0012）.After chronic DBS,the relative mRNA expression level of Casp3 was decreased （DBS vs.KA group：1.18 ± 0.37 vs.2.09 ± 0.46,P =0.0003）,and the relative mRNA expression level of Bcl2 was increased （DBS vs.KA group：0.92 ± 0.21 vs.0.48 ± 0.16,P =0.0004）.The protein expression levels of CASP3 （DBS vs.KA group：1.25 ± 0.26 vs.2.49 ± 0.38,P 〈 0.0001） and BAX （DBS vs.KA group：1.57 ± 0.49 vs.2.80 ± 0.63,P =0.0012） both declined in the DBS group whereas the protein expression level of BCL2 （DBS vs.KA group：0.78 ± 0.32 vs.0.36 ± 0.17,P =0.0086） increased in the DBS group.Conclusions：This study demonstrated that chronic ANT stimulation could exert a neuroprotective effect on hippocampal neurons.This neuroprotective effect is likely to be mediated by the inhibition of apoptosis in the epileptic hippocampus.
