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Sex modulates the outcome of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease

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Neural Regeneration Research 2023年第4期18卷 901-907页

作者： Tian-Shuo Yuan Ying-Chuan Chen De-Feng Liu Ruo-Yu Ma Xin Zhang Ting-Ting Du Guan-Yu Zhu Jian-Guo Zhang department of neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of functional neurosurgery Beijing Neurosurgical InstituteCapital Medical UniversityBeijingChina Beijing Key Laboratory of Neurostimulation BeijingChina

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 the

关键词： chronic effect deep brain stimulation generalized linear model initial effect motor symptoms non-motor symptoms Parkinson’s disease quality of life sex subthalamic nucleus

Advances in microvascular decompression for hemifacial spasm

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Journal of Otology 2015年第1期10卷 1-6页

作者： Zhiqiang Cui Zhipei Ling department of neurosurgery (functional) Chinese PLA General Hospital

Primary hemifacial spasm(HFS) is a disorder that causes frequent involuntary contractions in the muscles on one side of the face, due to a blood vessel compressing the nerve at its root exit zone(REZ) from the brainstem. Numerous prospective and retrospective case series have confirmed the efficacy of microvascular decompression(MVD) of the facial nerve in patients with HFS. However, while MVD is effective, there are still significant postoperative complications. In this paper, recent technological advances related to MVD(such as lateral spread response,brainstem auditory evokes potential, three dimensional time of flight magnetic resonance angiography, intraoperative neuroendoscopy) are reviewed for the purposes of improving MVD treatment efficacy and reducing postoperative complications.

关键词： Hemifacial spasm(HFS) Microvascular decompression(

Advances in brain imaging of neuropathic pain

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Chinese Medical Journal 2008年第7期121卷 653-657页

作者： CHEN Fu-yong TAO Wei LI Yong-jie department of functional neurosurgery Beijing Institute of Functional Neurosurgery Xuanwu Hospital Capital MedicalUniversity Beijing 100053 China

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.

关键词： magnetic resonance imaging function positron emission tomography neuropathic pain review

Neuropeptide Y protects cerebral cortical neurons by regulating microglial immune function

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Neural Regeneration Research 2014年第9期9卷 959-967页

作者： Qijun Li Changzheng Dong Wenling Li Wei Bu Jiang Wu Wenqing Zhao Graduate School Hebei Medical University department of functional neurosurgery Hebei General Hospital department of neurosurgery Third Hospital Hebei Medical University

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.

关键词： nerve regeneration microglia immunological activity neuropeptide Y interleukin-1β tumor necrosis factor-α INMDA neural regeneration

Evaluation of intraoperative MRI-assisted stereotactic brain tissue biopsy: a singlecenter experience in China

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Chinese Neurosurgical Journal 2019年第1期5卷 13-20页

作者： Chang-yu Lu Zong-sheng Xu Xun Ye department of neurosurgery Peking University International HospitalBeijingChina department of neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingChina

Background:This study aimed to investigate the value of high field-strength intraoperative magnetic resonance imaging(iMRI)-guided stereotactic biopsy in the surgery of intracranial space-occupying lesions.Methods:A total of 87 patients who underwent stereotactic biopsy of intracranial lesions in the Peking University International Hospital from March 2016 to August 2018 were retrospectively surveyed;among these,50 patients underwent MRI-guided stereotactic biopsy using the Leksell frame(iMRI group)and 37 cases received traditional stereotactic biopsy using the Leksell frame(control group).The accuracy rates and complications of the two groups were compared.Results:A 100%positive diagnosis was observed in all cases(n=50)in the iMRI group.In 4 cases,the biopsy site was clearly found to have deviated from the target point,and the biopsy was performed again.The control group had 33 cases(86.5%)with positive diagnosis.No severe complications like neural functional deficit were observed in the iMRI group,while two patients developed bleeding at the puncture site(1 case receiving surgery to remove the hematoma)in the control group.There were no deaths in either group.Conclusion:iMRI-assisted stereotactic biopsy can confirm the target position and adjust the puncture path in real time.Compared to the traditional stereotactic biopsy technique,the iMRI method has a higher positive diagnostic rate,though surgical trauma and complications have no significant difference.

关键词： High field-strength stereotactic technique Brain biopsy Intraoperative magnetic resonance

Deep brain stimulation of the nucleus basalis of Meynert modulates hippocampal-frontoparietal networks in patients with advanced Alzheimer’s disease

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Translational Neurodegeneration 2022年第1期11卷 148-160页

作者： Yin Jiang Tian-Shuo Yuan Ying-Chuan Chen Peng Guo Teng-Hong Lian Yu-Ye Liu Wei Liu Yu-Tong Bai Quan Zhang Wei Zhang Jian-Guo Zhang department of functional neurosurgery Beijing Neurosurgical InstituteCapital Medical UniversityBeijing 100070China department of functional neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Center for Cognitive Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Beijing Key Laboratory of Neurostimulation Beijing 100070China.

Background:Deep brain stimulation(DBS)of the nucleus basalis of Meynert(NBM)has shown potential for the treatment of mild-to-moderate Alzheimer’s disease(AD).However,there is little evidence of whether NBM-DBS can improve cognitive functioning in patients with advanced AD.In addition,the mechanisms underlying the modulation of brain networks remain unclear.This study was aimed to assess the cognitive function and the resting-state connectivity following NBM-DBS in patients with advanced AD.Methods:Eight patients with advanced AD underwent bilateral NBM-DBS and were followed up for 12 months.Clinical outcomes were assessed by neuropsychological examinations using the Mini-Mental State Examination(MMSE)and Alzheimer’s Disease Assessment Scale.Resting-state functional magnetic resonance imaging and positron emis-sion tomography data were also collected.Results:The cognitive functioning of AD patients did not change from baseline to the 12-month follow-up.Interestingly,the MMSE score indicated clinical efficacy at 1 month of follow-up.At this time point,the connectivity between the hippocampal network and frontoparietal network tended to increase in the DBS-on state compared to the DBS-off state.Additionally,the increased functional connectivity between the parahippocampal gyrus(PHG)and the parietal cortex was associated with cognitive improvement.Further dynamic functional network analysis showed that NBM-DBS increased the proportion of the PHG-related connections,which was related to improved cognitive performance.Conclusion:The results indicated that NBM-DBS improves short-term cognitive performance in patients with advanced AD,which may be related to the modulation of multi-network connectivity patterns,and the hippocampus plays an important role within these networks.

关键词： Alzheimer’s disease Deep brain stimulation Nucleus basalis of Meynert Hippocampal Frontoparietal functional connectivity

Effects of diazepam on glutamatergic synaptic transmission in the hippocampal CA1 area of rats with traumatic brain injury

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Neural Regeneration Research 2014年第21期9卷 1897-1901页

作者： Lei Cao Xiaohua Bie Su Huo Jubao Du Lin Liu Weiqun Song department of functional neurosurgery Xi’an Red Cross Hospital department of Rehabilitation Medicine Xuanwu HospitalCapital Medical University

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.

关键词： nerve regeneration traumatic brain injury fluid percussion injury excitatory synaptic transmission hippocampal CA1 pyramidal neurons paired-pulse facilitation miniature excitatory postsynaptic potential gamma-aminobutyric acid post-traumatic hyperactivity intracellular recording NSFC grant neural regeneration

Inhibition of the reinstatement of morphine-induced place preference in rats by high-frequency stimulation of the bilateral nucleus accumbens

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Chinese Medical Journal 2013年第10期126卷 1939-1943页

作者： MAYu CHEN Ning WANG Hui-min Meng Fan-gang ZHANG Jian-guo department of functional neurosurgery Beijing NeurosurgicalInstitute Capital Medical University Beijing 100050 China department of neurosurgery Beijing Tiantan Hospital CapitalMedical University Beijing 100050 China

Background Opiate addiction remains intractable in a large percentage of patients, and relapse is the biggest hurdle to recovery. Many studies have identified a central role of the nucleus accumbens （NAc） in addiction. Deep brain stimulation （DBS） has the advantages of being reversible, adjustable, and minimally invasive, and it has become a potential neurobiological intervention for addiction. The purpose of our study was to investigate whether high-frequency DBS in the NAc effectively attenuates the reinstatement of morphine seeking in morphine-primed rats. Methods A morphine-dependent group of rats was given increasing doses of morphine during conditioned place preference training. A control group of rats was given equal volumes of saline. After the establishment of this model, withdrawal syndromes were precipitated in these two groups by administering naloxone, and the differences in withdrawal symptoms between the groups were analyzed. Electrodes for DBS were implanted in the bilateral shell of the NAc in the experimental group. The rats were stimulated daily in the NAc for 5 hours per day over 30 days. Changes in the conditioned place preference test and withdrawal symptoms in the rats were investigated and place navigation studies were performed using the Morris water maze. The data were assessed statistically with one-way analysis of variance （ANOVA） followed by Tukey＇s tests for multiple post hoc comparisons. Results High-frequency stimulation of the bilateral NAc prevented the morphine-induced reinstatement of morphine seeking in the conditioned place preference test. The time spent in the white compartment by rats following 30 days of DBS （（268.25±25.07） seconds） was not significantly different compared with the time spent in the white compartment after relapse was induced by morphine administration （（303.29±34.22） seconds）. High-frequency stimulation of the bilateral NAc accelerated the innate decay of drug craving in morphine-dependent rats without significantly influencing learning and memory. Concl

关键词： stimulation, nucleus accumbens morphine, drug dependency

Anterior thalamic nuclei deep brain stimulation inhibits mossy fiber sprouting via 3′,5′-cyclic adenosine monophosphate/protein kinase A signaling pathway in a chronic epileptic monkey model

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Chinese Medical Journal 2021年第3期134卷 326-333页

作者： Ting-Ting Du Ying-Chuan Chen Guan-Yu Zhu De-Feng Liu Yu-Ye Liu Tian-Shuo Yuan Xin Zhang Jian-Guo Zhang department of functional neurosurgery Beijing Neurosurgical InstituteCapital Medical UniversityBeijing 100070China department of neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Beijing Key Laboratory of Neurostimulation Beijing 100070China

Background:Anterior thalamic nuclei(ATN)deep brain stimulation(DBS)is an effective method of controlling epilepsy,especially temporal lobe epilepsy.Mossy fiber sprouting(MFS)plays an indispensable role in the pathogenesis and progression of epilepsy,but the effect of ATN-DBS on MFS in the chronic stage of epilepsy and the potential underlying mechanisms are unknown.This study aimed to investigate the effect of ATN-DBS on MFS,as well as potential signaling pathways by a kainic acid(KA)-induced epileptic model.Methods:Twenty-four rhesus monkeys were randomly assigned to control,epilepsy(EP),EP-sham-DBS,and EP-DBS groups.KA was injected to establish the chronic epileptic model.The left ATN was implanted with a DBS lead and stimulated for 8 weeks.Enzyme-linked immunosorbent assay,Western blotting,and immunofluorescence staining were used to evaluate MFS and levels of potential molecular mediators in the hippocampus.One-way analysis of variance,followed by the Tukeypost hoc correction,was used to analyze the statistical significance of differences among multiple groups.Results:ATN-DBS is found to significantly reduce seizure frequency in the chronic stage of epilepsy.The number of ectopic granule cells was reduced in monkeys that received ATN stimulation(P<0.0001).Levels of 3′,5′-cyclic adenosine monophosphate(cAMP)and protein kinase A(PKA)in the hippocampus,together with Akt phosphorylation,were noticeably reduced in monkeys that received ATN stimulation(P=0.0030 andP=0.0001,respectively).ATN-DBS also significantly reduced MFS scores in the hippocampal dentate gyrus and CA3 sub-regions(allP<0.0001).Conclusion:ATN-DBS is shown to down-regulate the cAMP/PKA signaling pathway and Akt phosphorylation and to reduce the number of ectopic granule cells,which may be associated with the reduced MFS in chronic epilepsy.The study provides further insights into the mechanism by which ATN-DBS reduces epileptic seizures.

关键词： Anterior thalamic nuclei Deep brain stimulation Epilepsy Hippocampus Mossy fiber sprouting