Beijing Key Laboratory of Neurostimulation

Beijing, China

Beijing Key Laboratory of Neurostimulation

Beijing, China
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Chen Y.-C.,Capital Medical University | Shi L.,Capital Medical University | Zhu G.-Y.,Capital Medical University | Wang X.,Capital Medical University | And 6 more authors.
Brain Research | Year: 2017

Background The efficacy of anterior thalamic nuclei (ANT) deep brain stimulation (DBS) in mitigating epileptic seizures has been established. Though the neuroprotection of ANT-DBS has been illustrated, the seizure mitigating mechanism of ANT-DBS has not been thoroughly elucidated. In particular, the effect of ANT-DBS on neurogenesis has not been reported previously. Method Thirty-two male Sprague Dawley rats were randomly assigned to the following groups: sham-DBS-healthy (HL) (n = 8), DBS-HL (n = 8), sham-DBS-epilepsy (EP) (n = 8) and DBS-EP (n = 8). Normal saline and kainic acid were injected, respectively, into the former and later two groups, and seizures were monitored. One month later, rats received electrode implantation. Stimulation was exerted in the DBS group but not in the sham-DBS group. Next, all rats were sacrificed, and the ipsilateral hippocampus was dissected and prepared for quantitative real time PCR (qPCR) and western blot analysis in order to measure neuronal nuclear (NeuN), brain-derived neurotrophic factor (BDNF), doublecortin (DCX) and Ki-67 expressions. Results A 44.4% seizure frequency reduction was obtained after ANT-DBS, and no seizures was observed in healthy rats. NeuN, BDNF, Ki-67 and DCX expression levels were significantly decreased in the epileptic rats compared to healthy rats (P < 0.01 or P < 0.05). Obvious increases in NeuN, Ki-67 and DCX expressions were observed in epileptic and healthy rats receiving stimulation compared to rats receiving no stimulation (all Ps < 0.01). However, BDNF expression was not affected by ANT-DBS (all Ps > 0.05). Conclusions (1) ANT-DBS reduces neuronal loss during the chronic stage of epilepsy. (2) Neurogenesis is elevated by ANT-DBS in both epileptic and healthy rats, and this elevation may not be regulated via a BDNF pathway. © 2017


Zhang C.,Capital Medical University | Zhang C.,Beijing Key Laboratory of Neurostimulation | Hu W.-H.,Beijing Key Laboratory of Neurostimulation | Hu W.-H.,Capital Medical University | And 5 more authors.
Chinese Medical Journal | Year: 2015

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 of amyloid 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 than ANT 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. © 2015, Chinese Medical Association. All right reserved.


Yang A.-C.,Capital Medical University | Shi L.,Capital Medical University | Li L.-M.,Tsinghua University | Li L.-M.,Beijing Key Laboratory of Neurostimulation | And 9 more authors.
Brain Stimulation | Year: 2015

Background Stimulation of the anterior nucleus of the thalamus (ANT) is effective in seizure reduction, but the mechanisms underlying the beneficial effects of ANT stimulation are unclear. Objective To assess the beneficial effects of ANT stimulation on hippocampal neurons of epileptic monkeys. Methods Chronic ANT stimulation was applied to kainic acid-induced epileptic monkeys. Behavioral seizures were continuously monitored. Immunohistochemical staining and western blot assays were performed to assess the hippocampal injury and the effects of ANT stimulation. Results The frequency of seizures was 42.8% lower in the stimulation group compared with the sham-stimulation group. Immunohistochemical staining and western blot analyses indicated that neuronal loss and apoptosis were less severe and that neurofilament synthesis was enhanced in the stimulation monkeys compared with the sham-stimulation group. These data showed that the hippocampal injury was less severe in monkeys in the stimulation group than in those in the sham-stimulation group. Conclusions Our data suggest that chronic ANT stimulation may exert protective effects on hippocampal neurons and boost the regeneration of neuronal fibers. These effects may be closely related to the mechanisms of ANT stimulation in epilepsy treatment. © 2015 Elsevier Inc.


Zhang C.,Capital Medical University | Zhang C.,Beijing Key Laboratory of Neurostimulation | Wang Y.,Beijing Jingmei Group General Hospital | Wang X.,Capital Medical University | And 7 more authors.
Acta Neurochirurgica | Year: 2015

Background: Meningioangiomatosis (MA) is a rare cerebral lesion. Sporadic MA occasionally combines with meningioma (MA-M). The aim of the present study was to clarify whether MA-M and pure MA have clinical differences and to determine risk factors for unsatisfactory seizure outcomes in sporadic MA. Methods: We reported 14 sporadic MA cases in our center and conducted a literature review. We compared the demographic, clinical, imaging, electrophysiological and pathological features and surgical outcomes. Logistic regression analysis was performed to evaluate the risk factors for poor seizure outcomes. Results: MA-M cases showed a more prominent male predilection (4.2 times vs. 1.6 times, p = 0.04), a shorter duration of symptoms (2.8 ± 0.8 years vs. 5.2 ± 0.6 years, p = 0.02), and a lower seizure incidence (53.6 % vs. 89.3 %, p < 0.001) as compared to pure MA. A gyriform alteration on imaging was exclusively associated with pure MA. The Ki-67 was higher in the meningioma component than in the MA component in MA-M (1.2 ± 0.3 % vs. 6.1 ± 1.1 %, p < 0.001). Lesions located in the temporal lobe predicted poor seizure outcomes (p = 0.02, OR = 4.4, 95 % confidence interval, 1.24–15.89). Conclusion: Clinical differences may be caused by the different biological natures. MA-M seems to be a neoplastic lesion, while pure MA seems to be a non-neoplastic lesion. Long-term follow-up is required for MA-M. Because the coexistence of hippocampal sclerosis may explain the poor seizure outcomes of MA located in the temporal lobe, it is important to identify underlying hippocampal sclerosis and to perform complete resection. © 2015, Springer-Verlag Wien.


Wang X.,Capital Medical University | Wang X.,Beijing Key Laboratory of Neurostimulation | Wang Y.,Beijing Jingmei Group General Hospital | Zhang C.,Capital Medical University | And 12 more authors.
Brain Research | Year: 2016

Both endocannabinoids and dynorphin are feedback messengers in nervous system that act at the presynaptic nerve terminal to inhibit transmitter release. Many studies showed the cannabinoid-opioid cross-modulation in antinociception, hypothermia, sedation and reward. The aim of this study was to assess the influence of early application of cannabinoid type 1 (CB1) receptor antagonism SR141716A after brain injury on dynorphin-κ opioid receptor (KOR) system and the expression of metabotropic glutamate receptors (mGluRs) in a rat model of fluid percussion injury (FPI). Firstly, seizure latency induced by pentylenetetrazole was significantly prolonged 6 weeks after brain injury in group of SR141716A treatment. Then, PCR and western blot showed that SR141716A inhibited the long-term up-regulation of CB1 receptors in hippocampus. However, SR141716A resulted in long-term potentiation of dynorphin release and did not influence the up-regulation of KOR in hippocampus after brain injury. Furthermore, SR141716A reverse the overexpression of mGluR5 in the late stage of brain injury. We propose that during the induction of epileptogenesis after brain injury, early application of CB1 receptor antagonism could prevent long-term hyperexcitability by up-regulation of dynorphin-KOR system and prevention of mGluR5 induced epileptogenesis in hippocampus. © 2016 Elsevier B.V. All rights reserved.


Zhang C.,Capital Medical University | Zhang C.,Beijing Key Laboratory of Neurostimulation | Wei N.-L.,Lanzhou University | Wang Y.,Capital Medical University | And 5 more authors.
Neuroscience Letters | Year: 2015

The aim of this study was to assess the anti-obesity effects of nucleus accumbens shell (NAc-sh) deep brain stimulation (DBS) in diet-induced obese (DIO) and chow-fed (chow) rats. The influence of DBS on dopamine (DA) signaling in the NAc-sh was also evaluated. DIO and chow rats were subjected to DBS for 14 consecutive days. Food intake and weight gain were measured daily. The gene expression of the dopamine D1 and D2 receptors was evaluated by qPCR. In addition, the extracellular levels of DA and its metabolite, dihydroxyphenylacetic acid (DOPAC), were determined by microdialysis. We observed that chronic DBS induced significant reductions in total energy intake (596.0 ± 65.0. kcal vs. 1161.6 ± 22.2. kcal, p<. 0.001) and weight gain (1.45 ± 0.57% vs. 9.64 ± 0.38%, p<. 0.001) in DIO rats compared to sham-DIO rats. Up-regulated D2 receptor gene expression (2.43 ± 0.12 vs. 0.64 ± 0.04, p<. 0.001) and increased DA levels (2.73 ± 0.15. pmol/mL vs. 0.62 ± 0.05. pmol/mL, p<. 0.001) were observed in DIO rats compared to sham-DIO rats. DBS had no influence on food intake, weight gain, or DA neurotransmission in chow rats. Our results support an association of the anorexigenic effects of NAc-sh DBS with mesolimbic DA signaling and indicate that the positive alteration of DA function in DIO rats may be responsible for the different effects of DBS in DIO and chow rats. © 2015 Elsevier Ireland Ltd.


Wang X.,Capital Medical University | Wang X.,Beijing Key Laboratory of Neurostimulation | Zhang C.,Capital Medical University | Zhang C.,Beijing Key Laboratory of Neurostimulation | And 10 more authors.
Seizure | Year: 2016

Purpose To perform a systematic review and meta-analysis to identify predictors of postoperative seizure freedom in patients with magnetic resonance imaging (MRI)-negative temporal lobe epilepsy. Method Publications were screened from electronic databases (MEDLINE, EMBASE), epilepsy archives, and bibliographies of relevant articles that were written in English. We recorded all possible risk factors that might predict seizure outcome after surgery. We calculated odds ratio (OR) with corresponding 95% confidence intervals (95% CI) of predictors for postoperative seizure freedom. Heterogeneity was assessed with I2. All meta-analyses were performed using Review Manager. Results Epilepsy duration (OR = 2.57, 95% CI = 1.21-5.47, p < 0.05, I2 = 1%) and ictal or interictal electroencephalographic anomalies precisely localized in the ipsilateral temporal lobe (OR = 3.89, 95% CI = 1.66-9.08, p < 0.01, I2 = 0 and OR = 3.38, 95% CI = 1.57-7.25, p < 0.05, I2 = 0, respectively) were significantly associated with a higher rate of seizure freedom after surgery. However, the positron emission tomography (PET) results were not predictive of postoperative seizure freedom (OR = 2.11, 95% CI = 0.95-4.65, p = 0.06, I2 = 0). No significant difference in seizure freedom was observed between the positive and negative pathology groups (OR = 1.36, 95% CI = 0.70-2.63, p = 0.36, I2 = 0). Conclusions A shorter epilepsy duration and scalp electroencephalogram (EEG) signals localized precisely in the temporal lobe predicted a better seizure outcome in patients with MRI-negative temporal lobe epilepsy. © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.


Wang K.,Capital Medical University | Wang K.,Beijing Key Laboratory of Neurostimulation | Liu T.,Capital Medical University | Liu T.,Beijing Key Laboratory of Neurostimulation | And 9 more authors.
Frontiers in Neurology | Year: 2016

Introduction: Fluorine-18-fluorodeoxyglucose positron-emission tomography (18F-FDG-PET) is widely used to help localize the hypometabolic epileptogenic focus for presurgical evaluation of drug-refractory epilepsy patients. Two voxel-based brain mapping methods to interpret 18F-FDG-PET, statistical parametric mapping (SPM) and three-dimensional stereotactic surface projection (3D-SSP), improve the detection rate of seizure foci. This study aimed to compare the consistency of epileptic focus detection between SPM and 3D-SSP for 18F-FDG-PET brain mapping analysis. Methods: We retrospectively reviewed the clinical, electroecephalographic, and brain imaging results of 35 patients with refractory epilepsy. 18F-FDG-PET studies were revaluated by SPM, 3D-SSP, and visual assessment, and the results were compared to the magnetic resonance imaging (MRI) lesion location and to the presumed epileptogenic zone (PEZ) defined by video-electroencephalogram and other clinical data. A second consistency study compared PET analyses to histopathology and surgical outcomes in the 19 patients who underwent lesion resection surgery. Results: Of the 35 patients, consistency with the PEZ was 29/35 for SPM, 25/35 for 3D-SSP, 14/35 for visual assessment, and 10/35 for MRI. Concordance rates with the PEZ were significantly higher for SPM and 3D-SSP than for MRI (P < 0.05) and visual assessment (P < 0.05). Differences between SPM and 3D-SSP and between visual assessment and MRI were not significant. In the 19 surgical patients, concordance with histopathology/clinical outcome was 14/19 for SPM, 15/19 for 3D-SSP, 14/19 for visual assessment, and 9/19 for MRI (P > 0.05). A favorable Engel outcome (class I/II) was found in 16 of 19 cases (84%), and failure of seizure control was found in 3 of 19 patients (class III/IV). Conclusion: Voxel-based 18F-FDG-PET brain mapping analysis using SPM or 3D-SSP can improve the detection rate of the epileptic focus compared to visual assessment and MRI. Consistency with PEZ was similar between SPM and 3D-SSP; according to their own characteristics, 3D-SSP is recommended for primary evaluation due to greater efficiency and operability of the software, while SPM is recommended for high-accuracy localization of complex lesions. Therefore, joint application of both software packages may be the best solution for FDG-PET analysis of epileptic focus localization. © 2016 Wang, Liu, Zhao, Xia, Zhang, Qiao, Zhang and Meng.


PubMed | Capital Medical University and Beijing Key Laboratory of Neurostimulation
Type: Journal Article | Journal: Neuromodulation : journal of the International Neuromodulation Society | Year: 2015

The aim of this study was to report on four patients with craniocervical dystonia (CCD) treated with deep brain stimulation (DBS). In addition, we investigated the treatment efficacy and surgical outcome predictors by the review and analysis of previously published studies.Four patients with CCD underwent DBS of the globus pallidus internus (Gpi) or subthalamus nucleus (STN). PubMed and MEDLINE searches were performed to obtain detailed information on patients who underwent DBS for CCD. The primary efficacy endpoint was the change in the Burke-Fahn-Marsden Dystonia Rating Scale (movement and disability scores, BFMDRS-M/D) after surgery.Seventy-five patients were included in the pooled analysis, including 69 patients with Gpi-DBS and 6 patients with STN-DBS. The mean follow-up of time was 28.0 months after surgery. The mean BFMDRS-M score was 24.5 11.2 preoperatively and 8.1 5.7 postoperatively at the final follow-up evaluation, with a mean improvement of 66.9% (p < 0.001). The mean BFMDRS-D score was 8.1 4.6 preoperatively and 3.6 2.5 postoperatively, with a mean percentage improvement of 56.0% (p < 0.01). Positive correlations were found between each of the preoperative movement and disability scores and percentage of postoperative improvement (r = 0.247, p = 0.034; r = 0.331, p = 0.034, respectively).GPi/STN-DBS is an effective treatment for patients with medically refractory CCD, including those with severe preoperative symptoms. The age at CCD onset and the disease duration do not predict improvement in movement scores.

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