Key Laboratory of Neurodegenerative Diseases
Key Laboratory of Neurodegenerative Diseases
Fang X.,Capital Medical University |
Fang X.,Beijing Geriatric Medical Research Center |
Fang X.,Key Laboratory of Neurodegenerative Diseases |
Fang X.,Beijing Municipal Key Laboratory of Clinical Epidemiology |
And 18 more authors.
Neuroepidemiology | Year: 2016
The Cardiovascular and Cognitive Health Study (CCHS-Beijing) is a population-based study of cardiovascular disease (CVD) and cognitive impairment in adults aged 55 and older in Beijing. The main aims of the study are to investigate the prevalence rates of CVD, asymptomatic atherosclerosis, and cognitive impairment, as well as validate the risk factors related to the onset and development of CVD, Alzheimer's disease (AD) and mild cognitive impairment (MCI). The study was designed to detect the traditional and new risk factors in this age group. Participants were recruited randomly from residential regions in the greater Beijing municipality area based on the average levels of development in Beijing, China in 2012 (based on socioeconomic, demographic, and geographical characteristics). Thorough physical and laboratory examination were performed at baseline (also the cross-sectional survey) to identify the risk factors such as hypertension, dyslipidemia, diabetes, as well as newly defined risk factors like elevated homocysteine, high sensitivity C-reactive protein, and urine micro-albumin. Subclinical disease of the cerebral vasculature included atherosclerosis of carotid arteries, intracranial arteries, and retinal vessels. Subclinical cardiac diseases included left ventricular enlargement, arrhythmias, chamber hypertrophy and myocardial ischemia. Blood pressure was documented using the ankle-arm method. In addition, neuropsychological assessments were performed for all subjects aged 65 and above. Baseline evaluation began during the period August 2013 to December 2014. Follow-up examination will occur in 5 years. The initial and recurrent CVD, AD and MCI events will be verified and validated during the follow-up period. © 2016 S. Karger AG, Basel.
Ping S.-H.,Kunming University of Science and Technology |
Yue F.,Key Laboratory of Neurodegenerative Diseases |
Wang C.-Y.,Kunming University of Science and Technology |
Luo Y.,Kunming University of Science and Technology |
And 2 more authors.
Journal of Animal and Veterinary Advances | Year: 2012
The objective was to examine the effect of Permeable Cryoprotectant Agents (CPAs) on sperm cryopreservation of tree shrew. Epididymal sperm were surgically harvested from captured wild male tree shrews and cryopreserved with Tes-Tris-Egg yolk based cryodiluent (TTE) containing either of the four CPAs, Dimethyl Sulfoxide (DMSO), Ethylene Glycol (EG), Propylene Glycol (PG) and Glycerol (Gly) at concentrations of 1, 3, 6 and 10%, respectively. Sperm motility, acrosome integrity and fertility were assessed. In Experiment 1, sperm equilibrated at 4oC in TTE containing 1, 3 and 6% DMSO, respectively showed similar motility to that in TTE without CPA (p>0.05). Following the increase of concentration of CPAs and equilibration time (30-90min), the other CPAs reduced sperm motility (p<0.05). In Experiment 2, sperm frozen in TTE containing 3% DMSO showed the highest post-thaw motility (p<0.05) and recovery rate of motility (p<0.05) among groups. In Experiment 3, there were no differences in the fertilization rate of oocytes and the proportion of tree shrews yielding fertilized oocytes inseminated with fresh and thawed sperm frozen in TTE containing 3% DMSO (p>0.05). In conclusion, among the permeable CPAs tested, DMSO provided the best cryoprotective ability for captured wild tree shrew epididymal sperm. © Medwell Journals, 2012.
Cui Y.-Q.,Key Laboratory of Neurodegenerative Diseases |
Zhang L.-J.,Key Laboratory of Neurodegenerative Diseases |
Zhang T.,Capital Medical University |
Luo D.-Z.,Key Laboratory of Neurodegenerative Diseases |
And 5 more authors.
Clinical and Experimental Pharmacology and Physiology | Year: 2010
Summary 1. Microglial activation plays an important role in the pathogenesis of neurodegenerative diseases by producing various pro-inflammatory cytokines. Microglia-derived nitric oxide (NO) is critical for the lipopolysaccharide (LPS)-induced selective loss of dopaminergic neurons. 2. Fucoidan is a sulphated polysaccharide extracted from brown seaweeds. It has a variety of biological actions, including anticoagulant, antiviral and anti-inflammatory effects. The aim of the present study was to investigate the effects of fucoidan on LPS-induced cellular activation in microglia and to evaluate the inhibitory mechanisms involved. 3. To investigate the effects of fucoidan on LPS-induced cellular activation in microglia, primary microglial cells were preincubated with fucoidan (31.25, 62.5 and 125 μg/mL) for 10 min, followed by stimulation with LPS (0.01 μg/mL). Then, cell shape and NO production were determined 24 h after LPS stimulation, whereas inducible nitric oxide synthase (iNOS) mRNA and protein expression were determined at 6 and 18 h after LPS stimulation, respectively. To evaluate the inhibitory mechanisms involved, mitogen-activated protein kinase (MAPK) activation was also evaluated. 4. Lipopolysaccharide transformed cells into an amoeboid shape, whereas 62.5 μg/mL fucoidan inhibited this activation. Moreover, 125 μg/mL fucoidan significantly inhibited microglial NO production to 75% of that in LPS-treated group and also significantly diminished the expression of iNOS mRNA and protein by nearly 50%. Fucoidan (125 μg/mL) also suppressed phosphorylation of p38 and extracellular signal-regulated kinase (ERK) by approximately 50%, but not that of c-Jun N-terminal kinase. 5. The results provide the first evidence that fucoidan has a potent inhibitory effect against LPS-induced NO production by microglia. The results also suggest that this inhibitory action of fucoidan involves suppression of p38 and ERK phosphorylation. © 2010 Blackwell Publishing Asia Pty Ltd.
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 |
Wang R.,Capital Medical University |
And 24 more authors.
FEBS Journal | Year: 2014
T-LAK-cell-originated protein kinase (TOPK), a MAPKK-like kinase, is crucial for neural progenitor cell proliferation; however, the function of TOPK and the molecular mechanism underlying cerebral ischemia-reperfusion injury remains unknown. Therefore, we investigated the role of TOPK in experimental stroke. Sprague-Dawley rats underwent transient middle cerebral artery occlusion (tMCAO) and reperfusion, and TOPK small interfering RNA (siRNA) was delivered by intracerebroventricular injection at the beginning of MCAO. After TOPK overexpression and H2 stimulation in PC12 neuronal cells, antioxidative proteins, apoptosis-related proteins and signal pathways were detected by western blot analysis, the levels of the peroxidation products (malondialdehyde and 3-nitrotyrosine) were measured with ELISA. Phosphorylation of TOPK was increased in rat cortical neurons following tMCAO. TOPK overexpression in PC12 cells augmented levels of antioxidative proteins (peroxiredoxin 1 and 2, heme oxygenase 1 and manganese superoxide dismutase), as well as total superoxide dismutase activity, along with inhibition of malondialdehyde and 3-nitrotyrosine upon H2 stimulation. TOPK overexpression increased cell viability and reduced expression of caspase 3 and caspase 12 in PC12 cells in response to H2. The p-ERK level was increased by TOPK overexpression, and antioxidative protection afforded by TOPK was abolished by blocking the extracellular signal-regulated kinase pathway in PC12 cells. TOPK siRNA increased the infarct volume and reduced total superoxide dismutase activity in the cortex in vivo after MCAO. These data reveal that activating TOPK confers neuroprotection against focal cerebral ischemia-reperfusion injury by antioxidative function, in part through activation of the extracellular signal-regulated kinase pathway. © 2014 FEBS.
Liu P.,Capital Medical University |
Liu P.,Beijing Geriatric Medical Research Center |
Liu P.,Key Laboratory of Neurodegenerative Diseases |
Zhao H.,Capital Medical University |
And 25 more authors.
Stroke | Year: 2015
BACKGROUND AND PURPOSE - : We previously showed that the microRNA miR-424 protects against permanent cerebral ischemic injury in mice by suppressing microglia activation. This study investigated the role of miR-424 in transient cerebral ischemia in mice with a focus on oxidative stress-induced neuronal injury. METHODS - : Transient cerebral ischemia was induced in C57/BL6 mice by middle cerebral artery occlusion for 1 hour followed by reperfusion (ischemia/reperfusion). The miR-424 level in the peri-infarct cortex was quantified. Mice were also administered miR-424 angomir by intracerebroventricular injection. Cerebral infarct volume, neuronal apoptosis, and levels of oxidative stress markers and antioxidants were evaluated. In an in vitro experiment, primary cortical neurons were exposed to H2O2 and treated with miR-424 angomir, nuclear factor erythroid 2-related factor 2 siRNA, and superoxide dismutase (SOD) inhibitor; cell activity, lactate dehydrogenase release, malondialdehyde level, and manganese (Mn)SOD activity were then evaluated. RESULTS - : MiR-424 levels in the peri-infarct cortex increased at 1 and 4 hours then decreased 24 hours after reperfusion. Treatment with miR-424 decreased infarct volume and inhibited neuronal apoptosis after ischemia/reperfusion, reduced reactive oxygen species and malondialdehyde levels in the cortex, and increased the expression and activation of MnSOD as well as the expression of extracellular SOD and the redox-sensitive transcription factor nuclear factor erythroid 2-related factor. In neuronal cultures, miR-424 treatment abrogated H2O2-induced injury, as evidenced by decreased lactate dehydrogenase leakage and malondialdehyde level and increased cell viability and MnSOD activity; the protective effects of miR-424 against oxidative stress were reversed by nuclear factor erythroid 2-related factor knockdown and SOD inhibitor treatment. CONCLUSIONS - : MiR-424 protects against transient cerebral ischemia/reperfusion injury by inhibiting oxidative stress. © 2015 American Heart Association, Inc.
Liu X.,Capital Medical University |
Liu X.,Key Laboratory of Neurodegenerative Diseases |
Liu X.,Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases |
Zhao S.,Capital Medical University |
And 21 more authors.
Translational Stroke Research | Year: 2014
Remote ischemic postconditioning (RIPostC) has been proved to protect the brain from stroke, but the precise mechanism remains not fully understood. In the present study, we aimed to investigate whether RIPostC attenuates cerebral ischemia-reperfusion injury by abating endoplasmic reticulum (ER) stress response. CHOP, a multifunctional transcription factor in ER stress, regulates the expression of genes related to apoptosis, such as Bim and Bcl-2. Male SD rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion, and RIPostC was induced by three cycles of 10 min ischemia and 10 min reperfusion on bilateral femoral arteries immediately after ischemia. CHOP siRNA (CHOPi) and control siRNA (Coni) were injected into the right lateral ventricle 30 min before the beginning of ischemia. RIPostC, CHOPi, or RIPostC + CHOPi application reduced infarct volume, improved the neurological function, and decreased cell apoptosis. RIPostC increased the protein level of glucose-regulated protein 78 (GRP78) and decreased the protein level of phosphorylated-EIF2α, caspase-12, and CHOP. Furthermore, the expression of CHOP, Bim and cleaved-caspase-3 was decreased, while Bcl-2 expression was increased in response to application of RIPostC, CHOPi, or RIPostC + CHOPi. In sum, RIPostC protects against ischemia-reperfusion brain injury in rats by attenuating ER stress response-induced apoptosis. © 2014, Springer Science+Business Media New York.