Jiangsu Province Stroke Center for Diagnosis and Therapy

Nanjing, China

Jiangsu Province Stroke Center for Diagnosis and Therapy

Nanjing, China
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Yang H.,Nanjing University | Yang H.,Nanjing Medical University | Yang H.,Jiangsu Province Stroke Center for Diagnosis and Therapy | Yang H.,Nanjing Neuropsychiatry Clinic Medical Center | And 12 more authors.
International Immunopharmacology | Year: 2017

Esculentoside A (EsA) is a saponin isolated from the roots of Phytolacca esculenta. This study was designed to evaluate the pharmacological effects of EsA on lipopolysaccharide (LPS)-stimulated BV2 microglia and primary microglia cells. Our results indicated that EsA pretreatment significantly decreased LPS-induced production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2) and impeded LPS-mediated upregulation of pro-inflammatory mediators’ expression such as nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis factor-a (TNF-α) in both BV2 microglia and primary microglia cells. Moreover, EsA markedly suppressed nuclear factor-κB p65 (NF-κB p65) translocation by blocking IκB-α phosphorylation and degradation in LPS-treated BV2 cells. EsA also decreased phosphorylation level of mitogen-activated protein kinases (MAPKs) and inhibited NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome mediated caspase-1 activation in LPS-stimulated BV2 cells. Additionally, EsA decreased β-amyloid1–42 (Aβ1–42)-induced production of TNF-α, IL-1β and IL-6 in primary microglia. Thus, EsA might be a promising therapeutic agent for alleviating neuroinflammatory diseases. © 2017 Elsevier B.V.


Hui Z.,Nanjing University | Hui Z.,Nanjing Medical University | Hui Z.,Jiangsu Province Stroke Center for Diagnosis and Therapy | Sha D.-J.,Nanjing University | And 16 more authors.
BMC Complementary and Alternative Medicine | Year: 2017

Background: Panaxatriol saponins (PTS), an extract from the traditional Chinese herb Panax notoginseng, which has been used to treat ischemic stroke for many years in China. However, the mechanism underlying the effects of PTS remains unclear. This study aimed to determine whether PTS can protect against ischemic brain injury by promoting angiogenesis and to explore the possible mechanism by which it promotes angiogenesis. Methods: Middle cerebral artery occlusion (MCAO) was induced in rats, and neurological deficit scores and brain infarct volumes were assessed. Micro-Positron emission tomography (PET) was adopted to assess cerebral perfusion, and real-time PCR and western blotting were used to evaluate vascular growth factor and Sonic hedgehog (Shh) pathway component levels. Immunofluorescence staining was used to determine capillary densities in ischemic penumbrae. Results: We showed that PTS improved neurological function and reduced infarct volumes in MCAO rats. Micro-PET indicated that PTS can significantly increase 18F-fluorodeoxyglucose (18F-PDG) uptake by ischemic brain tissue and enhance cerebral perfusion after MCAO surgery. Moreover, PTS was able to increase capillary densities and enhance angiogenesis in ischemic boundary zones and up-regulate vascular endothelial growth factor (VEGF) and Angiopoietin-1 (Ang-1) expression by activating the Shh signaling pathway. Conclusion: These findings indicate that PTS exerts protective effects against cerebral ischemic injury by enhancing angiogenesis and improving microperfusion. © 2017 The Author(s).


Pan P.,Nanjing Medical University | Pan P.,Nanjing Southeast University | Zhan H.,Nanjing Medical University | Xia M.,Nanjing Medical University | And 6 more authors.
Neuroscience and Biobehavioral Reviews | Year: 2017

Studies of abnormal regional homogeneity (ReHo) in Parkinson's disease (PD) have reported inconsistent results. Therefore, we conducted a meta-analysis using the Seed-based d Mapping software package to identify the most consistent and replicable findings. A systematic literature search was performed to identify eligible whole-brain resting-state functional magnetic resonance imaging studies that had measured differences in ReHo between patients with PD and healthy controls between January 2000 and June 4, 2016. A total of ten studies reporting 11 comparisons (212 patients; 182 controls) were included. Increased ReHo was consistently identified in the bilateral inferior parietal lobules, bilateral medial prefrontal cortices, and left cerebellum of patients with PD when compared to healthy controls, while decreased ReHo was observed in the right putamen, right precentral gyrus, and left lingual gyrus. The results of the current meta-analysis demonstrate a consistent and coexistent pattern of impairment and compensation of intrinsic brain activity that predominantly involves the default mode and motor networks, which may advance our understanding of the pathophysiological mechanisms underlying PD. © 2016 Elsevier Ltd


Wang S.,Nanjing University | Yu L.,Nanjing Medical University | Yang H.,Nanjing University | Li C.,Nanjing University | And 6 more authors.
PLoS ONE | Year: 2016

Synaptic loss induced by beta-amyloid (Aβ) plays a critical role in the pathophysiology of Alzheimer's disease (AD), but the mechanisms underlying this process remain unknown. In this study, we found that oridonin (Ori) rescued synaptic loss induced by Aβ1-42 in vivo and in vitro and attenuated the alterations in dendritic structure and spine density observed in the hippocampus of AD mice. In addition, Ori increased the expression of PSD-95 and synaptophysin and promoted mitochondrial activity in the synaptosomes of AD mice. Ori also activated the BDNF/TrkB/CREB signaling pathway in the hippocampus of AD mice. Furthermore, in the Morris water maze test, Ori reduced latency and searching distance and increased the number of platform crosses in AD mice. These data suggest that Ori might prevent synaptic loss and improve behavioral symptoms in Aβ1-42-induced AD mice. © 2016 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Zhao Q.,Nanjing Medical University | Zhao Q.,Jiangsu Stroke Research Collaborative Group | Zhao Q.,Jiangsu Province Stroke Center for Diagnosis and Therapy | Li X.,Jiangsu Stroke Research Collaborative Group | And 38 more authors.
Neuroscience Bulletin | Year: 2016

The outcome of early intravenous thrombolysis for ischemic stroke in patients with atrial fibrillation (AF) is worse than that without thrombosis. How to increase the efficacy of intravenous thrombolysis for AF-related ischemic stroke remains largely unknown. In this study, we investigated factors that influence the effect of intravenous thrombolysis in these patients. Our results showed that thrombolysis was independently associated with a favorable outcome (P < 0.001) and did not influence the mortality of AF-related ischemic stroke, although it increased the risk of hemorrhage within 24 h after treatment. Risk factors for a poor outcome at admission were: heart failure (P = 0.045); high systolic pressure (P = 0.039); high blood glucose (P = 0.030); and a high National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001). Moreover, high systolic pressure at admission (P = 0.007), high blood glucose (P = 0.027), and a high NIHSS score (P < 0.001) were independent risk factors for mortality at 3 months. Besides thrombolysis, a high NIHSS score (P = 0.006) and warfarin taken within 48 h before stroke onset (P = 0.032) were also independent risk factors for symptomatic hemorrhage within 24 h after treatment. Ischemic stroke patients with AF benefited from intravenous thrombolysis with recombinant tissue plasminogen activator within 4.5 h after stroke. © 2016 Shanghai Institutes for Biological Sciences, CAS and Springer Science+Business Media Singapore


Chen Y.,Nanjing University | Han L.,Nanjing University | Li J.,Nanjing University | Li J.,Jiangsu University | And 8 more authors.
PLoS ONE | Year: 2015

Angiogenesisis a key restorative mechanism in response to ischemia, and pro-angiogenic therapy could be beneficial in stroke. Accumulating experimental and clinical evidence suggest that human urinary kallidinogenase (HUK) improves stroke outcome, but the underlying mechanisms are not clear. The aim of current study was to verify roles of HUK in postischemic angiogenesis and identify relevant mediators. In rat middle cerebral artery occlusion (MCAO) model, we confirmed that HUK treatment could improve stroke outcome, indicated by reduced infarct size and improved neurological function. Notably, the18 F-FDG micro-PET scan indicated that HUK enhanced cerebral perfusion in rats after MCAO treatment. In addition, HUK promotespost-ischemic angiogenesis, with increased vessel density as well as up-regulated VEGF andapelin/APJ expression in HUK-treated MCAO mice. In endothelial cell cultures, induction of VEGF and apelin/APJ expression, and ERK1/2 phosphorylation by HUK was further confirmed. These changes were abrogated by U0126, a selective ERK1/2 inhibitor. Moreover, F13A, a competitive antagonist of APJ receptor, significantly suppressed HUK-induced VEGF expression. Furthermore, angiogenic functions of HUK were inhibited in the presence of selective bradykinin B1 or B2 receptor antagonist both in vitro and in vivo. Our findings indicate that HUK treatment promotes post-ischemic angiogenesis and cerebral perfusion via activation of bradykinin B1 and B2 receptors, which is potentially due to enhancement expression of VEGF and apelin/APJ in ERK1/2 dependent way. © 2015 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Meng H.-L.,Nanjing University | Li X.-X.,Nanjing University | Chen Y.-T.,Nanjing University | Chen Y.-T.,Nanjing Medical University | And 13 more authors.
CNS Neuroscience and Therapeutics | Year: 2016

Aims: This study explored sFasL expression in neurons and the potential role of neuronal sFasL in modulating the microglial phenotypes. Methods: In vivo, middle cerebral artery occlusion (MCAO) was induced in both FasL-mutant (gld) and wild-type (wt) mice. In vitro, primary cortical neuron or microglia or coculture from wt/gld mice was subjected to oxygen glucose deprivation (OGD). sFasL level in the supernatant was evaluated by ELISA. Neuronal-conditioned medium (NCM) or exogenous sFasL was applied to primary microglia with or without FasL neutralizing antibody. Protein expression of JAK2/STAT3 and NF-κB pathways were determined by Western blot. The effect of microglia phenotype from wt/gld mice on the fate of ischemic neurons was further elucidated. Results: In vivo, compared with wild-type mice, M1 markers (CD16, CD32 and iNOS) were attenuated in gld mice after MCAO. In vitro, post-OGD neuron released more sFasL. Both post-OGD NCM and exogenous sFasL could trigger M1-microglial polarization. However, this M1 phenotype shift was partially blocked by utilization of FasL neutralizing antibody or gld NCM. Consistently, JAK2/STAT3 and NF-κB signal pathways were both activated in microglia after exogenous sFasL treatment. Compared with wild-type mice, M1-conditioned medium prepared from gld mice protected neuron against OGD injury. Conclusions: Ischemic neurons release sFasL, which contributes to M1-microglial polarization. The underlying mechanisms may involve the activation of JAK2/STAT3 and NF-κB signaling pathways. © 2016 John Wiley & Sons Ltd

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