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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of our study was to identify the perfusion MRI (pMRI) algorithm which yields a volume of hypoperfused tissue that best correlates with the acute clinical deficit as quantified by the NIH Stroke Scale (NIHSS) and therefore reflects critically hypoperfused tissue. A group of 20 patients with a first acute stroke and stroke MRI within 24 h of symptom onset were retrospectively analyzed. Perfusion maps were derived using four different algorithms to estimate relative mean transit time (rMTT): (1) cerebral blood flow (CBF) arterial input function (AIF)/singular voxel decomposition (SVD); (2) area peak; (3) time to peak (TTP); and (4) first moment method. Lesion volumes based on five different MTT thresholds relative to contralateral brain were compared with each other and correlated with NIHSS score. The first moment method had the highest correlation with NIHSS (r = 0.79, P < 0.001) followed by the AIF/SVD method, both of which did not differ significantly from each other with regard to lesion volumes. TTP and area peak derived both volumes, which correlated poorly or only moderately with NIHSS scores. Data from our pilot study suggest that the first moment and the AIF/SVD method have advantages over the other algorithms in identifying the pMRI lesion volume that best reflects clinical severity. At present there seems to be no need for extensive postprocessing and arbitrarily defined delay thresholds in pMRI as the simple qualitative approach with a first moment algorithm is equally accurate. Larger sample sizes which allow comparison between imaging and clinical outcomes are needed to refine the choice of best perfusion parameter in pMRI.
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PMID:The association between neurological deficit in acute ischemic stroke and mean transit time: comparison of four different perfusion MRI algorithms. 1631 62

Neuregulins are a family of growth factor domain proteins that are structurally related to the epidermal growth factor. Accumulating evidence has shown that neuregulins have cyto- and neuroprotective properties in various cell types. In particular, the neuregulin-1 Beta (NRG1-Beta) isoform is well documented for its antiinflammatory properties in rat brain after acute stroke episodes. Pentachlorophenol (PCP) is an organochlorine compound that has been widely used as a biocide in several industrial, agricultural, and domestic applications. Previous investigations from our laboratory have demonstrated that PCP exerts both cytotoxic and mitogenic effects in human liver carcinoma (HepG2) cells, primary catfish hepatocytes and AML 12 mouse hepatocytes. We have also shown that in HepG2 cells, PCP has the ability to induce stress genes that may play a role in the molecular events leading to toxicity and tumorigenesis. In the present study, we hypothesize that NRG1-Beta will exert its cytoprotective effects in PCP-treated AML 12 mouse hepatocytes by its ability to suppress the toxic effects of PCP. To test this hypothesis, we performed the MTT-cell respiration assay to assess cell viability, and Western-blot analysis to assess stress-related proteins as a consequence of PCP exposure. Data obtained from 48 h-viability studies demonstrated a biphasic response; showing a dose-dependent increase in cell viability within the range of 0 to 3.87 microg/mL, and a gradual decrease within the concentration range of 7.75 to 31.0 microg/mL in concomitant treatments of NRG1-Beta+PCP and PCP. Cell viability percentages indicated that NRG1-Beta+PCPtreated cells were not significantly impaired, while PCP-treated cells were appreciably affected; suggesting that NRG1-Beta has the ability to suppress the toxic effects of PCP. Western Blot analysis demonstrated the potential of PCP to induce oxidative stress and inflammatory response (c-fos), growth arrest and DNA damage (GADD153), proteotoxic effects (HSP70), cell cycle arrest as consequence of DNA damage (p53), mitogenic response (cyclin- D1), and apoptosis (caspase-3). NRG1-Beta exposure attenuated stress-related protein expression in PCP-treated AML 12 mouse hepatocytes. Here we provide clear evidence that NRG1-Beta exerts cytoprotective effects in AML 12 mouse hepatocytes exposed to PCP.
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PMID:Neuregulin 1-Beta cytoprotective role in AML 12 mouse hepatocytes exposed to pentachlorophenol. 1682 72

Perfusion weighted MRI has proven very useful for deriving hemodynamic parameters such as CBF, CBV and MTT. These quantities are important diagnostically, e.g. in acute stroke, where they are used to delineate ischemic regions. Yet the standard method for estimating CBF based on singular value decomposition (SVD) has been demonstrated to underestimate (especially high) flow components and to be sensitive to delays in the arterial input function (AIF). Furthermore, the estimated residue functions often oscillate. This compromises their physiological interpretation/basis and makes estimation of related measures such as flow heterogeneity difficult. In this study, we estimate perfusion parameters based on a vascular model (VM) which represents heterogeneous capillary flow and explicitly leads to monotonically decreasing residue functions. We use a fully Bayesian approach to obtain posterior probability distributions for all parameters. In simulation studies, we show that the VM method has less bias in CBF estimates than the SVD based method for realistic SNRs. This also applies to cases where the AIF is delayed. We employ our method to estimate perfusion maps using data from (i) a healthy volunteer and (ii) from a stroke patient.
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PMID:Bayesian estimation of cerebral perfusion using a physiological model of microvasculature. 1697 Nov 40

The present study was carried to investigate the effect of endothelin antagonist (TAK-044) in an in vitro model of stroke using primary neuronal culture. Hypoxia in neuronal culture was induced for 3 h using oxygen glucose deprivation (OGD) model, thereafter cells were reperfused. In separate group cultures were incubated with graded concentrations of TAK-044 (0.01, 0.1 and 1 microg/microl) for different time duration i.e. 6, 12 and 24 hours after reperfusion. Percent cell viability was assessed 24 h after reperfusion using MTT assay. It was observed that percent cell viability was reduced to 13.7 +/- 0.4% in the cells under 3 h hypoxic condition as compared to the cells under normal condition (100%). TAK-044 at the concentrations of 0.1 and 1 microg/microl, but not at 0.01 microg/microl showed significant (P<0.01) improvement in the % cell viability as compared to the cells in hypoxic condition. Percent cell viability at the concentration of 0.1 and 1 microg/microl for 24 h time duration after reperfusion were 54.8 +/- 3.2% and 75.4 +/- 1.8% respectively as compared to the cells under hypoxic condition (13.7 +/- 0.4%). The results demonstrate the neuroprotective effect of TAK-044 against neuronal damage caused by hypoxia induced in neuronal culture.
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PMID:Protective effect of endothelin antagonist (TAK-044) on neuronal cell viability in in vitro oxygen-glucose deprivation model of stroke. 1705 35

Heparin is a classic anticoagulant that is commonly used in the treatment of acute ischemic stroke (AIS). Its use remains controversial, however, due to the risk of cerebral hemorrhagic transformation. In addition to anticoagulant effects, diverse effects on transcription factors can be caused by heparin. Among the transcription factors potentially affected is nuclear factor kappa B (NF-kappaB), a protein that is reportedly related to the survival of cerebral endothelial cells. We investigated the effect of heparin on NF-kappaB activation and cell death following oxygen-glucose deprivation (OGD), an experimental model of AIS. We subjected bEnd.3 cells from a murine cerebral microvascular endothelial cell line to OGD. We examined the effect of heparin on OGD-induced NF-kappaB activation and its mechanism of action, using electrophoretic mobility shift assays, reporter gene analysis, real-time RT-PCR, Western blot analysis, and confocal microscopy. We also measured the effect of heparin on OGD-induced cell death using an MTT assay. Heparin inhibited both tumor necrosis factor alpha- and OGD-induced NF-kappaB activation. Heparin was taken up by endocytosis and then entered the nucleus. Heparin did not affect the nuclear translocation of NF-kappaB, but instead inhibited the DNA binding of NF-kappaB in the nucleus. Cells were more susceptible to OGD-induced cell death after heparin treatment. Besides producing an anticoagulation effect, heparin also inhibits NF-kappaB activation, resulting in increased susceptibility to OGD-induced cell death. This effect may be responsible for hemorrhagic transformation in patients following heparin treatment for AIS.
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PMID:Heparin inhibits NF-kappaB activation and increases cell death in cerebral endothelial cells after oxygen-glucose deprivation. 1787 98

Goal of initial imaging study for acute-stage ischemic stroke are to detect focal lesion accurately and to assist the therapeutic decision. With the goal in mind, we investigated feasibilities of MRI for acute-stage ischemic stroke. Firstly, we assessed whether diffusion weighted images (DWI) raised diagnostic accuracy for acute-stage ischemic stroke. We investigated how DWI study changes the diagnosis for the patients with neurological symptom in emergency room. Out of 164 patients who visit the emergency room with neurological symptom, sensitivity, specificity and efficiency for ischemic stroke diagnosis before DWI study were 0.87, 0.85 and 0.89 respectively. DWI raised them to 0.99, 0.98 and 0.99. These result proves feasibility of DWI on diagnosis of acute-stage ischemic stoke. Secondly, we assess whether DWI and perfusion imaging (PI) can provide any information about fate of acute ischemic lesion. We compared the relationships between DWI and PI parameters (ADC, rCBF, MTT, rCBV) and tissue outcome (infracted or survived). In patients with successful recanalization, best predictor was ADC and the cut-off value was 0.90 against contra-lateral hemisphere. In patients without recanalization, rCBF at 0.66 against contra-lateral hemisphere predicted the pathological fate most accurately. This simple guidepost can be help therapeutic decision of acute-stage stroke.
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PMID:[What stroke MRI provides to us]. 1821 Aug 36

There is a current interest in dietary compounds (such as trans-resveratrol) that can inhibit or reverse oxidative stress, the common pathway for a variety of brain disorders, including Alzheimer's disease and stroke. The objective of the present study was to investigate the effects of resveratrol, under conditions of oxidative stress induced by H(2)O(2), on acute hippocampal slices from Wistar rats. Here, we evaluated cell viability, extracellular lactate, glutathione content, ERK(MAPK) activity, glutamate uptake and S100B secretion. Resveratrol did not change the decrease in lactate levels and in cell viability (by MTT assay) induced by 1mM H(2)O(2), but prevented the increase in cell permeability to Trypan blue induced by H(2)O(2). Moreover, resveratrol per se increased total glutathione levels and prevented the decrease in glutathione induced by 1mM H(2)O(2). The reduction of S100B secretion induced by H(2)O(2) was not changed by resveratrol. Glutamate uptake was decreased in the presence of 1mM H(2)O(2) and this effect was not prevented by resveratrol. There was also a significant activation of ERK1/2 by 1mM H(2)O(2) and resveratrol was able to completely prevent this activation, leading to activity values lower than control levels. The impairments in astrocyte activities, induced by H(2)O(2), confirmed the importance of these cells as targets for therapeutic strategy in brain disorders involving oxidative stress. This study reinforces the protective role of resveratrol and indicates some possible molecular sites of activity of this compound on glial cells, in the acute damage of brain tissue during oxidative stress.
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PMID:Resveratrol protects against oxidative injury induced by H2O2 in acute hippocampal slice preparations from Wistar rats. 1883 40

Conventional diesel and palm oil methyl esters were blended in 6 ratios (0, 10, 30, 50, 75 and 100% of biodiesel by volume) and fed into an unmodified 4-stroke engine with a constant output power. The semi-volatile and particulate products in the exhaust were collected separately and their biological toxicities evaluated by both Microtox test and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The Microtox test indicates that the TUVs (toxicity unit per liter exhaust sampled, TU/L-exhaust) in the semi-volatile extracts were 3 to 5 times those of the particulate extracts. Diesel particulates had the highest unit toxicity, TUW (toxicity unit per microg soluble organic fraction of particulate, TU/microg particle SOF) of all of the other biodiesel blends. According to the Microtox tests results, the effect of biodiesel blending in MTT assay demonstrated higher toxicity in the semi-volatile products than the particulates.
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PMID:Biological toxicities of emissions from an unmodified engine fueled with diesel and biodiesel blend. 1898 12

A disintegrin and metalloproteinase-17 (ADAM17) is involved in proteolytic ectodomain shedding of several membrane-bound growth factors and cytokines. The expression and activity of ADAM17 increase under some pathological conditions such as stroke and glioma. ADAM17 promotes neural progenitor cell migration and contributes to stroke-induced neurogenesis after stroke and brain tumor growth and invasion. In the present study, we sought to elucidate whether ADAM17 contributes to breast cancer progression and its mechanisms. To this end, we examined the role of ADAM17 in the proliferation, invasion and tube formation of MDA-MB-231 breast cancer cells in vitro. Stable transfection of the MDA-MB-231 cell line with either a plasmid for overexpression of human ADAM17, or a siRNA to ADAM17 was employed in this study to establish high or low ADAM17 expression in breast cancer cells, respectively. For study of mechanism, the ADAM17 inhibitor TAPI-2 and the PI3K-AKT inhibitor LY294002 were used to counteract high ADAM17 expression or the activated PI3K-AKT pathway. Proliferation of MDA-MB-231 breast cancer cells were tested by MTT, Bromodeoxyuridine incorporation assay, growth curve and sulforhodamine B assay. Matrigel invasion assays were used to assess the ability of MDA-MB-231 cells to penetrate the Extra Cellular Matrix. A Matrigel tube formation assay was performed to test capillary tube formation ability. EGFR-PI3K-Akt pathway activation in MDA-MB-231 cells under different ADAM17 expression levels were tested by western blot and ELISA. Our data show that ADAM17 promotes the MDA-MB-231 malignant phenotype by increased proliferation, invasion and angiogenesis. TGFalpha, VEGF secretion and VEGF expression was increasing by ADAM17 and counteracted by ADAM17 siRNA, TAPI-2 and LY294002 in MDA-MB-231 cells. ADAM17 activated, whereas ADAM17 siRNA, TAPI-2 and LY294002 deactivated the EGFR-PI3K-AKT signal pathway, which correlated with MDA-MB-231 cell malignant phenotype changes. This study suggests ADAM17 contributes to breast cancer progression through activation of the EGFR-PI3K-AKT signal pathway.
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PMID:ADAM17 promotes breast cancer cell malignant phenotype through EGFR-PI3K-AKT activation. 1943 Feb 1

DL-3-n-butylphthalide (NBP) has been used for stroke treatment in China for years. Recently, we found that NBP can reduce the incidence of stroke and have protective action on cerebral microvessels, suggesting a direct action of NBP on endothelial cells. However, it is difficult to evaluate the direct action of NBP on endothelial cells in vivo because of the interactions of endothelial cells with other types of neuronal cells. Therefore, we investigated whether NBP protects against oxygen glucose deprivation (OGD)-induced cell injury in an immortalized human umbilical vein endothelial cells (HUVEC) in vitro. Cells were exposed to OGD, leading to endothelial damage. Endothelial injury was assessed by measuring MTT and the changes in chromatin morphology. Mitochondrial superoxide, mitochondrial membrane potential and mitochondrial morphology were assessed using MitoSOX Red. Rhodamine 123 and MitoTracker, respectively. Nitrosative stress was assessed by measuring the production of peroxynitrite. The activity of superoxide dismutase (SOD) is evaluated using SOD assay kit-WST. The expression of hypoxia inducible factor-1 alpha (HIF-1alpha) was assessed at the protein level by immunofluorescence and Western blotting. NBP at doses between 0.01 and 100 micromol/L dose-dependently protected against OGD-induced cell death. In addition, NBP attenuated OGD-induced mitochondria superoxide, cellular formation of peroxynitrite, and decrease in SOD activity, mitochondria fragmentation and loss of mitochondrial membrane potential. In parallel, NBP enhanced OGD-induced HIF-1alpha expression. This study demonstrates that NBP can protect HUVEC against OGD-induced oxidative/nitrosative stress, mitochondrial damage and subsequent cell death. This protective effect is, at least in part, associated with its enhancement on OGD-induced HIF-1alpha expression.
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PMID:DL-3-n-butylphthalide protects endothelial cells against oxidative/nitrosative stress, mitochondrial damage and subsequent cell death after oxygen glucose deprivation in vitro. 1961 17


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