Guan-Yu Zhu

Potential Protective Effects of Chronic Anterior Thalamic Nucleus Stimulation on Hippocampal Neurons in Epileptic Monkeys

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.

Deep brain stimulation of the anterior nucleus of the thalamus reverses the gene expression of cytokines and their receptors as well as neuronal degeneration in epileptic rats.

BACKGROUND Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is effective in seizure control. However, the mechanisms remain unclear. METHODS Sixty-four rats were randomly assigned to the control group, the kainic acid (KA) group, the sham-DBS group and the DBS group. Video-electroencephalogram (EEG) was used to monitor seizures. Quantitative real time PCR (qPCR) was applied for detecting interleukin-1 beta (IL-1β), IL-1 receptor (IL-1R), IL-6, IL-6 receptor (IL-6R), gp130, tumor necrosis factor-alpha (TNF-α), TNF-receptor 1 (TNF-R1) and TNF-receptor 2 (TNF-R2) expression 12h after the establishment of an epileptic model. The neuronal structural degeneration in the hippocampus was evaluated with transmission electron microscopy (TEM) at this same time point. RESULTS The seizure frequency was 48.6% lower in the DBS group compared with the sham-DBS group (P<0.01). The expression of IL-1β, IL-1R, IL-6, IL-6R, gp130, TNF-α and TNF-R1 was elevated in both the KA and the sham group compared with the control group (all Ps<0.01). Additionally, ANT-DBS was able to reverse this gene expression pattern in the DBS group compared with the sham-DBS group (all Ps<0.01). There was no significant difference in TNF-R2 expression among the four groups. The neuronal structural degeneration in the KA group and the sham-DBS group was more severe than that in the control group (injury scores, all Ps<0.01). ANT-DBS was also capable of relieving the degeneration compared with the sham-DBS group (injury score, P<0.01). CONCLUSIONS This study demonstrated that ANT-DBS can reduce seizure frequency in the early stage in epileptic rats as well as relieve the pro-inflammatory state and neuronal injury, which may be one of the most effective mechanisms of ANT-DBS against epileptogenesis.

Effects of anterior thalamic nuclei deep brain stimulation on neurogenesis in epileptic and healthy rats

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.

Delayed responses of subthalamic nucleus to deep brain stimulation in patients with Parkinson's disease

Cases 6 3 Male/Female 1(16.7%)/5(83.3%) 1(33.3%)/2(66.7%) Age 66.3 ± 4.4 years 69.0 ± 6.6 years Disease History 8.5 ± 3.3 years 8.7 ± 2.5 years Daily Madopar Dose 0.75e2.25 pills 1.50e3.00 pills Bilateral/Unilateral Symptom 4(66.7%)/2(33.3%) 3(100%)/0(0) Preoperative UPDRS-III score 36.8 ± 6.9 41.3 ± 7.6 Target posterior to RN 0.7 ± 0.4 mm 0.9 ± 0.5 mm STN MER length 7.5 ± 1.2 mm 5.1 ± 1.0 mm Bilateral/Unilateral Delayed Responses 2(33.3%)/4(66.7%) 3(100%)/0(0) UPDRS-III score 1 year after surgery 23.5 ± 7.7 # 27.0 ± 7.0 #

Anterior thalamic nuclei deep brain stimulation reduces disruption of the blood–brain barrier, albumin extravasation, inflammation and apoptosis in kainic acid-induced epileptic rats

Abstract Objective The therapeutic efficacy of anterior thalamic nuclei deep brain stimulation (ATN-DBS) against seizures has been largely accepted; however, the effects of ATN-DBS on disruption of the blood–brain barrier (BBB), albumin extravasation, inflammation and apoptosis still remain unclear. Methods Rats were distributed into four treatment groups: physiological saline (PS, N = 12), kainic acid (KA, N = 12), KA-sham-DBS (N = 12) and KA-DBS (N = 12). Seizures were monitored using video-electroencephalogram (EEG). One day after surgery, all rats were sacrificed. Then, samples were prepared for quantitative real-time PCR (qPCR), western blot, immunofluorescence (IF) staining, and transmission electron microscopy to evaluate the disruption of the BBB, albumin extravasation, inflammation, and apoptosis. Result Because of the KA injection, the disruption of the BBB, albumin extravasation, inflammation and apoptosis were more severe in the KA and the KA-sham-DBS groups compared to the PS group (all Ps < 0.05 or < 0.01). The ideal outcomes were observed in the KA-DBS group. ATN-DBS produced a 46.3% reduction in seizure frequency and alleviated the disruption of the BBB, albumin extravasation, inflammatory reaction and apoptosis in comparison to the KA-sham-DBS group (all Ps < 0.05 or < 0.01). Conclusion (1) Seizures can be reduced using ATN-DBS in the epileptogenic stage. (2) ATN-DBS can reduce the disruption of the BBB and albumin extravasation. (3) ATN-DBS has an anti-inflammatory effect in epileptic models.

Ultrahigh-Magnitude Brain Magnetic Resonance Imaging Scan on Rhesus Monkeys With Implanted Deep Brain Stimulation Hardware: ULTRAHIGH MRI ON MONKEYS WITH DBS HARDWARE

Patients with implanted deep brain stimulation (DBS) hardware are prohibited from undergoing magnetic resonance imaging (MRI) scans at magnitudes greater than 1.5 T to avoid potential MRI‐related heating injury. Whether DBS devices are compatible with higher field MRI scanning is unknown. This study aimed to investigate whether 7.0 T and 3.0 T MRI scans can be safely performed on rhesus monkeys with implanted DBS devices.

Anterior nucleus of thalamus stimulation inhibited abnormal mossy fiber sprouting in kainic acid-induced epileptic rats

BACKGROUND Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) has demonstrated antiepileptic efficacy, especially for mesial temporal lobe epilepsy (MTLE). Mossy fiber sprouting (MFS) is involved in the pathogenesis of MTLE, and Sema-3A and GAP-43 are pivotal regulators of MFS. This study investigated the effects of ANT-DBS on MFS and expression levels of Sema-3A and GAP-43 as a possible mechanism for seizure suppression. METHODS Adult male Sprague-Dawley rats were randomly divided into four groups: (1) control (saline injection), (2) KA (kainic acid injection), (3) KA + Sham-DBS (electrode implantation without stimulation), and (4) KA + DBS (electrode implantation with stimulation). Video electroencephalography (EEG) was used to ensure model establishment and monitor seizure frequency, latency, and severity (Racine stage). Chronic ANT stimulation was conducted for 35 days in the KA + DBS group, and MFS compared to the other groups by quantitative Timm staining. Sema-3A and GAP-43 expression levels in the hippocampal formation were evaluated in all groups with western blot. RESULTS The latency period was significantly prolonged and spontaneous seizure frequency reduced in the KA + DBS group compared to KA and KA + Sham-DBS groups. Staining scores for MFS in CA3 and dentate gyrus (DG) were significantly lower in the KA + DBS group. The KA + DBS group also exhibited decreased GAP-43 expression and increased Sema-3A expression compared to KA and KA + Sham-DBS groups. CONCLUSION These results suggest that ANT-DBS extends the latent period following epileptogenic stimulation by impeding MFS through modulation of GAP-43 and Sema-3A expression.

Could cough be an intraoperative indicator for venous air embolism in deep brain stimulation surgeries?: experiences from a large case series

BackgroundDeep brain stimulation (DBS) surgery is usually performed with the patients located in a half-sitting position. Therefore, complications associated with such position accompany, such as venous air embolism (VAE), et al. However, because the patients are fully conscious during the surgery, they may have observable manifestations related to the complications that are otherwise inconspicuous in generally anesthetic surgeries. Thus, we designed this study to investigate the intraoperative manifestations of the potentially dangerous complication of VAE in the DBS surgery.MethodsThe medical records of a series of 705 consecutive patients who underwent DBS surgery in our hospital have been retrospectively reviewed. The clinical features, intraoperative manifestations and treatment of these patients were analyzed for evidence of VAE. The correlation between the cough intensity and other clinical features were investigated.ResultsEvidence of VAE were found in 16 patients. Statistical analyses showed that severe cough is associated with greater age (p = 0.045), longer coughing time (p = 0.001), more intensive tremor (p = 0.032), more complaints (p = 0.036), greater influences (p = 0.009), more treatment (p = 0.003) and longer hospitalization (p = 0.003).ConclusionsIntraoperative intense and unremitting cough may be a noticeable indicator of possible VAE. Early recognition and effective management are essential to prevent unfavorable outcomes in such cases.

An Electrode-preserved Patient after Bilateral Intracranial Hematoma Induced by Deep Brain Stimulation

To the Editor: Deep brain stimulation (DBS) is widely used in Parkinsons disease. Here, we report a bilateral hemorrhage case related to subthalamic nucleus (STN)-DBS. In this case, we preserved the electrode, and the curative effect is still satisfied after 2 years. A 66-year-old female was admitted to Beijing Tiantan Hospital with 10 years Parkinsons disease (Unified Parkinson Disease Rating Scale [UPDRS] part III [motor examination] score 12/41 [on/off medication]). She was also diagnosed as hypertension for 4 years and treated with nifedipine controlled-release tablets (Adalat GITS, Bayer, Germany). The systolic pressure was usually between 130 and 150 mmHg with a large fluctuation nevertheless. The highest systolic pressure was reported reaching 180 mmHg. Bilateral STN-DBS was conducted and one time of microelectrode recording in both sides. The operation was finished successfully. However after 8 h, the patient was found unconscious with unequal pupils and a blunt light reflex. Computed tomography (CT) indicated hematoma in right frontal lobe [Figure 1a]. An emergency operation was performed. The bone flap around the electrode was kept, and the electrode was preserved. Surprisingly, CT showed that new hematoma in left frontal lobe the next day [Figure 1b]. Considering the patients age and the hemorrhage were not large, we adopted conservative treatment, as a result, the hemorrhage became smaller under dynamic view [Figure 1c]. The patient was discharged 2 weeks later. The stimulator (Activa PC, 37601, Medtronic, USA) was turned on 5 months after the operation. The UPDRS-III score 5/29 (on/off stimulation) demonstrated that the electrode works well after 2 years. Figure 1 Postoperative computed tomography data indicating the disease evolution in this case. (a) A computed tomography scan 8 h after the first operation; (b) A computed tomography scan 8 h after the second operation; (c) A computed tomography scan 13 day after ... Because DBS is generally safe, preoperative preparation may not get enough attention. However, some complications are fatal like this case. Bilateral hematoma after DBS is rare to see, and we are regretful for not sending the pathology of the hematoma. According to the previous article, hypertension is the most significant risk factor for intracranial hemorrhage (ICH),[1] but it does not raise enough concern, especially when accompany with other diseases and with large fluctuation.[2,3] During and after DBS, we should control the blood pressure in a stable state for patients who have large blood pressure variability to decrease the ICH tendency. Some patients in our center are diagnosed as amyloidosis which is related to hematoma after DBS surgery because of the fibroid necrosis and microaneurysms.[4] Susceptibility weighted imaging is effective in detecting hemorrhage in the central nervous system before surgery.[5] If the hematoma appears, we need to protect the bone flap and the electrode during the hematoma clearance operation. The therapeutic effect will be kept if the two sides of the electrode are stable. Once the electrode is pulled out, it is difficult to place again due to the moved structure and the absorption of the hematoma in the chronic stage. In most cases, we remove the electrode as the hematoma may push the electrode and the electrode is negative for the hematoma absorption. However in this case, we kept the electrode and the therapeutic effect is good after 2 years. This indicates that electrode can be preserved even the hematoma emerged after surgery. Furthermore, our experience showed that we should wait a longer time before turning on the stimulator since the electrode needs a longer time to interact with the surrounding tissues. Financial support and sponsorship This study was supported by grants from the National Natural Science Foundation of China (No. 81301183), the Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding (No. ZYLX201305) and the Scientific Research Common Program of Beijing Municipal Commission of Education (No. KZ201510025029). Conflicts of interest There are no conflicts of interest.

Error Analysis and Some Suggestions on Animal Stereotactic Experiment from Inaccuracy of Rhesus Macaques Atlas

Guan‐Yu Zhu1, Ying‐Chuan Chen2, Lin Shi1, An‐Chao Yang1, Yin Jiang3, Xin Zhang3, Jian‐Guo Zhang1,2,3,4 1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China 2Department of Functional Neurosurgery, Beijing Tianan Hospital, Capital Medical University, Beijing 100050, China 3Department of Functional Neurosurgery, Beijing Neurosurgical Institute, Capital Medical University, Beijing 100050, China 4Beijing Key Laboratory of Neurostimulation, Beijing 100050, China