Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases

Beijing, China

Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases

Beijing, China
SEARCH FILTERS
Time filter
Source Type

Wang R.,Capital Medical University | Wang R.,Beijing Institute for Brain Disorders | Wang R.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases | Zhao H.,Capital Medical University | And 18 more authors.
Neurological Research | Year: 2017

Objective: Erythropoietin (EPO) confers potent neuroprotection against ischemic injury through a variety of mechanisms. However, the protective effect of EPO on axons after cerebral ischemia in adult mice is rarely covered. The purpose of this study was to investigate the potential neuroprotective effects of EPO on axons in mice after cerebral ischemia. Methods: A total of 30 adult male C57 BL/6 mice were treated with EPO (5000 IU/kg) or vehicle after transient middle cerebral artery occlusion (MCAO). The mortality rate of each experimental group was calculated. Neurological function was assessed by Rota-rod test. Frozen sections from each mouse brain at 14 days after reperfusion were used to evaluate the fluorescent intensity of myelin basic protein (MBP) and neurofilament 200 (NF-200). Immunofluorescence staining and Western blotting were used to assess the protein level of β-amyloid precursor protein (β-APP) and glial fibrillary acidic protein (GFAP), a marker of mature astrocytes. The protein levels of the myelin-derived growth inhibitory proteins, neurite growth inhibitor-A (Nogo-A), myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMG) were also examined by Western blot after MCAO. Results: The survival rate of the vehicle group 14 days after cerebral ischemia-reperfusion was 50%, which increased to 80% after EPO treatment at the start of reperfusion. EPO improved neurobehavioral outcomes at days 3 and 7 after MCAO was compared with the vehicle group (P < 0.05). Furthermore, EPO ameliorated demyelination, demonstrated by upregulation of the MBP/NF-200 ratio. Meanwhile, increased levels of β-APP, GFAP, Nogo-A, and MAG after MCAO were reduced by EPO treatment (P < 0.05). Conclusion: EPO treatment attenuates axonal injury and improves neurological function after cerebral ischemia in adult mice. © 2017 Informa UK Limited, trading as Taylor & Francis Group


Chen X.,Capital Medical University | Chen X.,China National Clinical Research Center for Neurological Diseases | Chen X.,Beijing Institute for Brain Disorders | Chen X.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases | And 6 more authors.
Oncotarget | Year: 2017

Nuclear factor-kappaB (NF-κB) has a vital role in cell survival and inhibition of NF-κB had proven to be an efficient therapeutic pathway for various cancers though little is known about the underlying mechanism. Previously we identified regulator of calcineurin 1 (RCAN1) as an endogenous inhibitor of NF-κB signaling pathway in lymphoma. In the present study, we have solid data to show that RCAN1 can inhibit the nuclear translocation of NF-κB protein then affect the activity of NF-κB signaling pathway in glioma cells. Overexpression of RCAN1 markedly reduced glioma cells viability. We further found that the suppressing glioma cell growth was closely related to the pro-apoptosis effect, not by inhibiting proliferation by the arrest of cell cycle. Our study implicated a novel therapeutic approach for glioma by RCAN1 through inhibition of NF-κB signaling.


Tong X.,Capital Medical University | Tong X.,China National Clinical Research Center for Neurological Diseases | Tong X.,Beijing Institute for Brain Disorders | Tong X.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases | And 16 more authors.
BMJ Open | Year: 2017

Introduction: Although microsurgical resection is currently the first-line treatment modality for arteriovenous malformations (AVMs), microsurgery of these lesions is complicated due to the fact that they are very heterogeneous vascular anomalies. The Spetzler-Martin grading system and the supplementary grading system have demonstrated excellent performances in predicting the risk of AVM surgery. However, there are currently no predictive models based on multimodal MRI techniques. The purpose of this study is to propose a predictive model based on multimodal MRI techniques to assess the microsurgical risk of intracranial AVMs. Methods and analysis: The study consists of 2 parts: the first part is to conduct a single-centre retrospective analysis of 201 eligible patients to create a predictive model of AVM surgery based on multimodal functional MRIs (fMRIs); the second part is to validate the efficacy of the predictive model in a prospective multicentre cohort study of 400 eligible patients. Patient characteristics, AVM features and multimodal fMRI data will be collected. The functional status at pretreatment and 6 months after surgery will be analysed using the modified Rankin Scale (mRS) score. The patients in each part of this study will be dichotomised into 2 groups: those with improved or unchanged functional status (a decreased or unchanged mRS 6 months after surgery) and those with worsened functional status (an increased mRS). The first part will determine the risk factors of worsened functional status after surgery and create a predictive model. The second part will validate the predictive model and then a new AVM grading system will be proposed. Ethics and dissemination: The study protocol and informed consent form have been reviewed and approved by the Institutional Review Board of Beijing Tiantan Hospital Affiliated to Capital Medical University (KY2016-031-01). The results of this study will be disseminated through printed media. © 2017 Published by the BMJ Publishing Group Limited.


Zhao Y.,Capital Medical University | Zhao Y.,Beijing Geriatric Medical Research Center | Zhao Y.,Key Laboratory of Neurodegenerative Diseases | Zhao Y.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases | And 24 more authors.
Stroke | Year: 2014

BACKGROUND AND PURPOSE - : Zinc has been reported to possess both neurotoxic and neuroprotective capabilities. The effects of elevated intracellular zinc accumulation following transient focal cerebral ischemia remain to be fully elucidated. Here, we investigated whether removing zinc with the membrane-permeable zinc chelator, N,N,N′,N′-tetrakis(2- pyridylmethyl)ethylenediamine (TPEN), would decrease the intracellular levels of zinc in the ischemic tissue, leading to reduced brain damage and improved neurological outcomes. METHODS - : Rats were pretreated with TPEN or vehicle before or after a 90-minute middle cerebral artery occlusion. Cerebral infarct volume, neurological functions, neuronal apoptosis, poly(ADP-ribose) polymerase activity, and cytosolic labile zinc were assessed after ischemia and reperfusion. RESULTS - : Cerebral ischemia caused a dramatic cytosolic labile zinc accumulation in the ischemic tissue, which was decreased markedly by TPEN (15 mg/kg) pretreatment. Chelating zinc lead to reduced infarct volume compared with vehicle-treated middle cerebral artery occlusion rats, accompanied by much improved neurological assessment and motor function, which were sustained for 14 days after reperfusion. We also determined that reducing zinc accumulation rescued neurons from ischemia-induced apoptotic death by reducing poly(ADP-ribose) polymerase-1 activation. CONCLUSIONS - : Ischemia-induced high accumulation of intracellular zinc significantly contributed to ischemic brain damage through promotion of neuronal apoptotic death. Removing zinc may be an effective and novel approach to reduce ischemic brain injury. © 2014 American Heart Association, Inc.


Zhao H.,Capital Medical University | Zhao H.,Beijing Geriatric Medical Research Center | Zhao H.,Key Laboratory of Neurodegenerative Diseases of Ministry of Education | Zhao H.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases | And 29 more authors.
Brain Research | Year: 2014

The present study was designed to investigate the potential role of miR-23a-3p in experimental brain ischemia-reperfusion injury. Cerebral ischemia reperfusion was induced by transient middle cerebral artery occlusion (MCAO) for 1 h in C57/BL6 mice. And miR-23a-3p angomir was transfected to upregulate the miR-23a-3p level. Our results showed that miR-23a-3p levels were transiently increased at 4 h after reperfusion in the peri-infarction area, while markedly increased in the infarction core at reperfusion 4 h and 24 h. Importantly, in vivo study demonstrated that miR-23a-3p angomir treatment through intracerebroventricular injection markedly decreased cerebral infarction volume after MCAO. Simultaneously, miR-23a-3p reduced peroxidative production nitric oxide (NO) and 3-nitrotyrosine (3-NT), and increased the expression of manganese superoxide dismutase (MnSOD). In vitro study demonstrated that miR-23a-3p decreased hydrogen peroxide (H2O2)-induced lactate dehydrogenase (LDH) leakage dose-dependently, and reduced protein levels of activated caspase-3 in neuro-2a cells. In addition, miR-23a-3p reduced H2O2-induced production of NO and 3-NT dose-dependently, and reversed the decreased activity of total SOD and MnSOD in neuro-2a cells. Our study indicated that miR-23a-3p suppressed oxidative stress and lessened cerebral ischemia-reperfusion injury. © 2014 Elsevier B.V. All rights reserved.


Tong X.,Capital Medical University | Tong X.,China National Clinical Research Center for Neurological Diseases | Tong X.,Beijing Institute for Brain Disorders | Tong X.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases | And 40 more authors.
World Neurosurgery | Year: 2016

Objective To identify whether age, sex, and lesion location are associated with initial presentation in patients with brain arteriovenous malformations (AVMs). Methods Collected data of 3299 consecutive patients with AVM treated at Beijing Tiantan Hosptial from January 1980 to January 2015 were analyzed. The variables assessed were age at diagnosis, sex, AVM location, and mode of initial presentation. Results Initial presentation was AVM hemorrhage in 57.9%, seizure in 20.9%, chronic headache in 14.9%, focal neurologic deficit in 5.2%, and incidental in 1.2%. Younger age and female sex were associated with initial hemorrhage (all P < 0.05). Hemorrhage was more likely to occur in patients with AVMs in the basal ganglia, the corpus callosum, the ventricles, the cerebellum, and the brainstem (all P < 0.05). Male sex was associated with initial seizure (P < 0.05). Initial seizure was more likely to occur in patients with AVMs in the frontal, temporal, parietal, frontotemporal, and frontoparietal lobe (all P < 0.05). Compared with frontal AVMs, temporal AVMs were more likely to present with hemorrhage (P < 0.05) and less likely to present with seizure (P < 0.05). AVMs involving the occipital lobe were more likely to present with chronic headaches (P < 0.05). Conclusions Initial AVM presentation varied with patient age, sex, and AVM locations. Younger age, female sex, and deep and infratentorial locations may be associated with initial hemorrhage. Male sex and frontal, temporal, and parietal AVM locations may be predictors of initial seizure. Chronic headache was more likely to occur in patients with AVMs involving the occipital lobe. © 2016 Elsevier Inc.

Loading Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases collaborators
Loading Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases collaborators