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Neural Regeneration Research 2010年第13期5卷 993-998页

作者： Chaoshi Niu Yongfei Dong Ge Gao Department of Neurosurgery Anhui Provincial Hospital of Anhui Medical University Hefei 230001 Anhui Province China Molecular Neurobiology & Neural Regeneration and Repairing Laboratory Anhui Provincial Stereotactic Neurosurgical Institute Hefei 230001 Anhui Province China

BACKGROUND： Vascular endothelial growth factor （VEGF） induces bone marrow-derived mesenchymal stem cell （BMSC） differentiation into vascular endothelial-like cells and promotes BMSC migration toward gliomas. However, the molecular mechanisms by which VEGF induces BMSC differentiation and migration remain poorly understood. OBJECTIVE; To investigate the role of platelet-derived growth factor （PDGF） receptor （PDGFR） in BMSC differentiation and migration induced by VEGE DESIGN, TIME AND SETTING： A parallel, controlled, in vitro experiment was performed at the Molecular Neurobiology ＆ Neural Regeneration and Repairing Laboratory, anhui Provincial Hospital of anhui Medical University, China from June 2008 to March 2009. MATERIALS： U87 glioma cells were purchased from Shanghai institutes for Biological Sciences; mouse anti-human PDGFR and VEGF receptor （VEGFR） monoclonal antibodies were purchased from Peprotech, USA. METHODS： Isolated BMSCs were precultured with neutralizing antibody for VEGFR-1, VEGFR-2, PDGFR-α, and PDGFR-β to block biological activity of related receptors, followed by induced differentiation with 50μg/L VEGF. BMSCs induced with 50μg/L VEGF alone served as the VEGF-induced group. The control group remained untreated. MAIN OUTCOME MEASURES： Cell surface markers were identified by flow cytometry; BMSC surface cytokine receptor expression was detected by reverse transcription-polymerase chain reaction; the Transwell model was used to observe cell migration. RESULTS： After blocking the PDGFR, VEGF did not induce BMSC cell surface marker CD-31 or von Willebrand factor （vWF） expression. However, inhibition with VEGF receptor blocking agents, VEGF induced BMSCs to express CD-31 and vWE Following inhibition of the PDGFR, the number of cells migrating through the polycarbonate membrane Transwell chamber was decreased, as well as the number of BMSCs migrating to glioma cells. However, through the use of VEGF receptor blocking agents, the number of migrating cells remained unchanged. VEGF preculture increased t

关键词： vascular endothelial growth factor platelet-derived growth factor receptor bone marrow-derived mesenchymal stem cells glioma immunofluorescence

Early cisternal fibrinolysis is more effective than rescue spasmolysis for the prevention of delayed infarction after subarachnoid haemorrhage

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Stroke & Vascular Neurology 2022年第2期7卷 108-113页

作者： Roland Roelz Christian Scheiwe Jürgen Grauvogel Istvan Csok Volker Arnd Coenen Jürgen Beck Peter C Reinacher Department of Neurosurgery Medical Center-University of FreiburgFreiburgGermany Department of stereotactic and functional Neurosurgery Medical Center-University of FreiburgFaculty of MedicineFreiburgGermany Fraunhofer institute for Laser Technology(ILT) AachenGermany

Background To compare the efficacy of two different concepts of cisternal therapy—PREVENTIVE fibrinolysis plus on-demand spasmolysis versus RESCUE spasmolysis—for the prevention of cerebral vasospasm(CVS)and delayed cerebral infarction(DCI)in patients with aneurysmal subarachnoid haemorrhage(aSAH).Methods Retrospective analysis of 84 aSAH patients selected for cisternal therapy for DCI prevention.66 high-risk patients received PREVENTIVE cisternal therapy to enhance blood clearance.Either stereotactic catheter ventriculocisternostomy(STX-VCS)or intraoperative placement of a cisterno-ventriculostomy catheter(CVC),followed by fibrinolytic cisternal lavage using urokinase was performed.In case of vasospasm,nimodipine was applied intrathecally.22 low-risk patients who developed CVS against expectations were selected for STX-VCS as RESCUE intervention for cisternal spasmolysis with nimodipine.Rates of DCI and mean flow velocities of daily transcranial Doppler(TCD)ultrasonographies were evaluated.Results Despite a higher prespecified DCI risk,patients selected for PREVENTIVE intervention primarily aiming at blood clearance had a lower DCI rate compared with patients selected for intrathecal spasmolysis as a RESCUE therapy(11.3%vs 18.2%).After intrathecal treatment onset,CVS(TCD>160 cm/s)occurred in 45%of patients with PREVENTIVE and 77%of patients with RESCUE therapy(p=0.013).A stronger response of CVS to intrathecal nimodipine was observed in patients with PREVENTIVE intervention as the mean CVS duration after start of intrathecal nimodipine was 3.2 days compared with 5.8 days in patients with RESCUE therapy(p=0.026).Conclusions PREVENTIVE cisternal therapy directed at blood clearance is more effective for the prevention of CVS and delayed infarction compared with cisternal RESCUE spasmolysis.

关键词： prevention spasmolysis infarction

Deep brain stimulation in the treatment of tardive dystonia

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Chinese Medical Journal 2006年第9期119卷 789-792页

作者： ZHANG Jian-guo ZHANG Kai WANG Zhong-cheng Department of Neurosurgery Beijing Tiantan Hospital ＆ Functional Neurosurgical Department Beijing Neurosurgical Institute Beijing 100050 China

Dystonia refers to a clinical syndrome in which sustained involuntary muscle contractions result in twisting and repetitive movements, or abnormal postures. Secondary dystonia is associated with acquired or exogenous causes, hereditary neurologic syndromes or neurodegenerative disorders. Tardive dystonia is a special type of secondary dystonia due to exposure to certain medicines such as neuroleptics, with a chronic and persistent extrapyramidal symptoms.

关键词： deep brain stimulation subthalamic nucleus tardive dystonia

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

Brain gliomas Biological characteristics and correlation with the status of adjacent corticospinal tracts

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Neural Regeneration Research 2010年第17期5卷 1347-1352页

作者： Chaoshi Niu Xiaorui Fei Changxin Wang Jiaming Mei Ying Liu Min Ding Department of Neurosurgery Anhui Provincial HospitalAnhui Medical UniversityHefei 230001Anhui ProvinceChina Molecular Neurobiology & Neural Regeneration and Repairing Laboratory Anhui Provincial Stereotactic Neurosurgical InstituteHefei 230001Anhui ProvineChina Department of Radiology Anhui Provincial Hospital Anhui Medical UniversityHefei 230001Anhui ProvinceChina Department of Pathology Anhui Provincial HospitalAnhui Medical UniversityHefei 230001Anhui ProvinceChina

Malignant behaviors of brain gliomas include proliferation and infiltration.It remains unclear which behavior influences the status of adjacent corticospinal tracts.Diffusion tensor imaging can show the status of brain white matter fiber tracts.Ki-67 and CD44/matrix metalloproteinase 9 are sensitive markers for reflecting the proliferation and infiltration of tumor cells.The present study analyzed pre-operative diffusion tensor images of 24 patients with pathologically confirmed World Health Organization glioma（Ⅰ-Ⅳ）.We observed lapse,infiltration and destruction of the peri-tumor corticospinal tract following reconstruction,and simultaneously detected the expression of Ki-67,CD44/matrix metalloproteinase 9 in samples.Expression of CD44 and matrix metalloproteinase 9was not significantly correlated to the status of the peri-tumor corticospinal tract（r = 1.597,4.859;P = 0.450,0.088）,while Ki-67 expression significantly correlated to its status（r= 6.590,P = 0.037）.These findings demonstrate that highly proliferative gliomas result in damage to the peripheral corticospinal tract.

关键词： brain gliomas corticospinal tracts diffusion tensor imaging fiber tract pathology biology

Temporal lobe epilepsy animal model established by stereotaxic microinjection of kainic acid

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Neural Regeneration Research 2008年第4期3卷 436-440页

作者： Zheng Wu Qi Xu Ruobing Qian Feng Yu Lian Yu Dehu Kong Liecheng Wang Department of Physiology Anhui Medical University Hefei 230032 Anhui Province China Department of Neurosurgery Anhui Provincial Hospital Anhui Medical University Hefei 230001 Anhui Province China Department of Neurology Anhui Provincial Hospital Anhui Medical University Hefei 230001 Anhui Province China anhui Provincial stereotactic neurosurgical institute Anhui Provincial Hospital Anhui Medical University Hefei 230001China

BACKGROUND： Kainic acid can be used to induce a model of epilepsy by systemic injection, such as intraperitoneal or subcutaneous injection. Individual rats have different responses to kainic acid, therefore high doses of drug are required and the success rate of model induction is low. It is necessary to develop an improved method to establish a temporal lobe epilepsy （TLE） animal model. OBJECTIVE： To explore an economic, stable and efficient method of establishing a TLE animal model. DESIGN, TIME AND SETTING： A completely randomized, controlled study. The experiments were performed in the Cellular Function Laboratory of the Physiology Department, anhui Medical University from March to July 2007. MATERIALS： Twenty adult male Wistar rats, weighing 230-260 g, were provided by the Experimental Animal Centre of Nanjing Medical University. Kainic acid was purchased from Sigma in USA. Type SN-2 stereotaxic apparatus was made by Narishge in Japan. METHODS： Wistar rats were randomly divided into a kainic acid （KA） group （n = 12） and a normal saline （NS） group （n = 8）. For intrahippocampal microinjection, a burr hole was drilled in the skull at the following stereotaxic coordinates： anteroposterior （AP） 4.1 mm caudal to bregma; lateral （ML） 4.2 mm right lateral to the midline. Rats in the KA group were injected with 2.5 μL KA （0.4 g/L） into the center of the CA3 region, while in the NS group the same volume of NS was injected into the same site. MAIN OUTCOME MEASURES： Both groups were monitored under a video capture system for 12 weeks to record spontaneous seizures. Intracranial eletroencepholograph （IEEG） recordings in vivo were performed after the behavioral observations. After the IEEG recordings, hippocampi were processed into coronal sections. Nissl and Timm stainings were then performed to observe and confirm pathology. RESULTS： Twenty rats were involved in the final analysis. Behavioral observations： the eadiest spontaneous onset of epilepsy appeared 2 weeks after injection of KA. Eight rats had spontaneous onset

关键词： epilepsy temporal lobe kainic acid microinjections

Acute Fornix Deep Brain Stimulation Improves Hippocampal Glucose Metabolism in Aged Mice

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Chinese Medical Journal 2018年第5期131卷 594-599页

作者： Xiu Wang Wen-Hart HU Kai Zhang Jun-Jian Zhou De-Feng Liu Mei-Yu Zhang Jian-Guo Zhang Department of Neurosurgery Beijing Tian Tan Hospital Capital Medical University Beijing 100050 China stereotactic and functional Neurosurgery Laboratory Beijing Neurosurgical Institute Capital Medical University Beijing 100050 China Beijing Key Laboratory of Neurostimulation Beijing 100050 China Experimental Research Center China Academy of Traditional Chinese Medicine Beijing 100700 China

Background： A beneficial memory effect of acute formix deep brain stimulation （DBS） has been reported in clinical studies. The aim of this study was to investigate the acute changes in glucose metabolism induced by fornix DBS. Methods： First, the Morris water maze test and novel object recognition memory test were used to confirm declined memory in aged mice （C57BL/6, 20-22 months old）. Then, four groups of mice were used as follows： aged mice with stimulation （n = 12）, aged mice with sham-stimulation （n = 8）, adult mice （3-4 months old） with stimulation （n = 12）, and adult mice with sham-stimulation （n = 8）. lpsilateral hippocampal glucose metabolism and glutamate levels were measured in vivo by microdialysis before, during, and after fornix DBS treatment. Histological staining was used to verify the localization of electrodes and mice with inaccurate placement were excluded from subsequent analyses. The effects of fornix DBS on extracellular glucose, lactate, pyruvate, and glutamate levels over time were analyzed by repeated-measures analysis of variance followed by Fisher＇s least significant difference post hoc test. Results： The aged mice had a higher basal lactate/pyruvate ratio （LPR） and lactate/glucose ratio （LGR） than the adult mice （LPR： 0.34 ± 0.04 vs. 0.13 ± 0.02, t = 4.626, P 〈 0.0001 ; LGR： 6.06± 0.59 vs. 4.14 ± 0.36, t = 2.823, P 〈 0.01 ）. Fomix DBS decreased the ipsilateral hippocampal pyruvate and lactate levels （P 〈 0.05）, but the glucose levels were not obviously changed in aged mice. Similarly, the LGR and LPR also decreased in aged mice after fornix DBS treatment （P 〈 0.05）. Glucose metabolism in adult mice was not significantly influenced by tbrnix DBS. In addition, fornix DBS significantly decreased the ipsilateral hippocampal extracellular levels of glutamate in aged mice （P 〈 0.05）, while significant alterations were not found in the adult mice. Conclusions： The present study provides experimental evidence that fornix DBS could significantly improve bippocampal glucose metabolism in aged m

关键词： Deep Brain Stimulation Fornix Glucose Metabolism Memory Decline

Surgical treatment of refractory epilepsy, secondary to central nervous system infection

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Neural Regeneration Research 2011年第5期6卷 396-400页

作者： Yunpeng Wang Guojun Zhang Lixin Cai Yongjie Li Beijing functional neurosurgical institute Xuanwu Hospital of Capital Medical University Beijing 100053 China

Previous studies have focused on medial temporal lobe epilepsy secondary to central nervous system infections. Several large-sample analyses of multi-lobe injuries or complications of medial temporal lobe epilepsy have been reported. The present study selected 29 patients （10 males and 19 females with a mean age of 18 years） with refractory epilepsy secondary to central nervous system infections （meningitis in 8, encephalitis in 21） from Beijing functional neurosurgical institute from May 2006 to August 2008. All patients underwent computer tomography or magnetic resonance imaging, as well as electroencephalogram examinations; cortical electrodes were embedded in 11 patients. In addition, 13 （45%） patients underwent anterior temporal Iobectomy, and 16 （56%） underwent extratemporal corcticectomy. Results showed that 18 （62%） patients obtained favorable outcomes following surgical treatment, including 80% with temporal lobe epilepsy and 50% with extratemporal epilepsy. Central nervous system infection was not a contraindication for epilepsy treatment, and identification of epileptic foci proved to be crucial. In addition, a young age at infection, as well as prolonged latent period from time of infection to initial afebrile seizure, were 2 predictive factors for all patients. Cortical electrodes significantly increased the detection rate of epileptic foci, but did not improve prognosis of foci excision.

关键词： epilepsy meningitis encephalitis surgical treatment

Behavioral Effects of Deep Brain Stimulation of the Anterior Nucleus of Thalamus, Entorhinal Cortex and Fornix in a Rat Model of Alzheimer＇s Disease

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Chinese Medical Journal 2015年第9期128卷 1190-1195页

作者： Chao Zhang Wen-Han Hu De-Long Wu Kai Zhang Jian-Guo Zhang Department of Neurosurgery Beijing Tian Tan Hospital Capital Medical University Beijing 100050 China Beijing Key Laboratory of Neurostimulation Beijing 100050 China stereotactic and functional Neurosurgery Laboratory Beijing Neurosurgical Institute Capital Medical University Beijing 100050 China Department of Neurosurgery Xiamen Fifth Hospital Xiamen University Xiamen Fujian 361101 China

Background：Recent clinical and preclinical studies have suggested that deep brain stimulation （DBS） can be used as a tool to enhance cognitive functions.The aim of the present study was to investigate the impact of DBS at three separate targets in the Papez circuit,including the anterior nucleus of thalamus （ANT）,the entorhinal cortex （EC）,and the fornix （FX）,on cognitive behaviors in an Alzheimer＇s disease （AD） rat model.Methods：Forty-eight rats were subjected to an intrahippocampal injection ofamyloid peptides 1-42 to induce an AD model.Rats were divided into six groups：DBS and sham DBS groups of ANT,EC,and FX.Spatial learning and memory were assessed by the Morris water maze （MWM）.Recognition memory was investigated by the novel object recognition memory test （NORM）.Locomotor and anxiety-related behaviors were detected by the open field test （OF）.By using two-way analysis of variance （ANOVA）,behavior differences between the six groups were analyzed.Results：In the MWM,the ANT,EC,and FX DBS groups performed differently in terms of the time spent in the platform zone （F（2.23） =6.04,P ＜ 0.01）,the frequency of platform crossing （F（2,23） =11.53,P ＜ 0.001）,and the percent time spent within the platform quadrant （F（2,23） =6.29,P ＜ 0.01）.In the NORM,the EC and FX DBS groups spent more time with the novel object,although the ANT DBS group did not （F（2,23） =10.03,P ＜ 0.001）.In the OF,all of the groups showed a similar total distance moved （F（1.42） =1.14,P =0.29）and relative time spent in the center （F（2,42） =0.56,P =0.58）.Conclusions：Our results demonstrated that DBS of the EC and FX facilitated hippocampus-dependent spatial memory more prominently thanANT DBS.In addition,hippocampus-independent recognition memory was enhanced by EC and FX DBS.None of the targets showed side-effects of anxiety or locomotor behaviors.

关键词： Anterior Thalamic Nuclei Deep Brain Stimulation Entorhinal Cortex Fornix Memory