The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Paul K. Witting - One of the best experts on this subject based on the ideXlab platform.
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protective effect of a synthetic anti oxidant on neuronal cell apoptosis resulting from Experimental Hypoxia re oxygenation injury
Journal of Neurochemistry, 2006Co-Authors: Ben S. Rayner, Simon J. Myers, T Hong T Duong, Paul K. WittingAbstract:Oxidative stress is associated with the pathology of acute and chronic neurodegenerative disease. Cultured neuronal cells exposed to Hypoxia-reoxygenation (H/R) injury, as a model for stroke, yield a burst of reactive oxygen species (ROS) as measured with electron paramagnetic resonance (EPR) spectroscopy in combination with spin trapping. Added superoxide dismutase inhibited spin-adduct formation verifying that superoxide radical anion was formed in neuronal cells following H/R injury. The intracellular ADP/ATP ratio increased rapidly over the first 5 h following injury and this was due primarily to the decreased cellular pools of ATP, consistent with the notion that H/R promotes mitochondrial dysfunction leading to decreased ATP reserve and increased ROS formation. As an early response to the enhanced oxidative stress, genes encoding for Hypoxia-inducible factor 1-alpha (HIF1-alpha), inducible haemoxygenase-1 (HO-1), and the oxygen-sensor neuroglobin increased significantly. Up-regulation of the HO-1 gene was paralleled by increased HO protein expression and activity. Despite this cellular response, apoptosis increased significantly following H/R injury indicating that the endogenous anti-oxidant defenses were unable to protect the cells. In contrast, addition of a phenolic anti-oxidant, bisphenol (BP), prior to H/R injury, inhibited ROS production and gene regulation and significantly decreased neuronal cell apoptosis. Added BP was converted stoichiometrically to the corresponding diphenoquinone indicating the synthetic anti-oxidant effectively decreased oxidative stress through a radical scavenging mechanism. Together, these data indicate that BP has the potential to act as a neuro-protective drug.
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Protective effect of a synthetic anti‐oxidant on neuronal cell apoptosis resulting from Experimental Hypoxia re‐oxygenation injury
Journal of neurochemistry, 2006Co-Authors: Ben S. Rayner, T. T. Hong Duong, Simon J. Myers, Paul K. WittingAbstract:Oxidative stress is associated with the pathology of acute and chronic neurodegenerative disease. Cultured neuronal cells exposed to Hypoxia-reoxygenation (H/R) injury, as a model for stroke, yield a burst of reactive oxygen species (ROS) as measured with electron paramagnetic resonance (EPR) spectroscopy in combination with spin trapping. Added superoxide dismutase inhibited spin-adduct formation verifying that superoxide radical anion was formed in neuronal cells following H/R injury. The intracellular ADP/ATP ratio increased rapidly over the first 5 h following injury and this was due primarily to the decreased cellular pools of ATP, consistent with the notion that H/R promotes mitochondrial dysfunction leading to decreased ATP reserve and increased ROS formation. As an early response to the enhanced oxidative stress, genes encoding for Hypoxia-inducible factor 1-alpha (HIF1-alpha), inducible haemoxygenase-1 (HO-1), and the oxygen-sensor neuroglobin increased significantly. Up-regulation of the HO-1 gene was paralleled by increased HO protein expression and activity. Despite this cellular response, apoptosis increased significantly following H/R injury indicating that the endogenous anti-oxidant defenses were unable to protect the cells. In contrast, addition of a phenolic anti-oxidant, bisphenol (BP), prior to H/R injury, inhibited ROS production and gene regulation and significantly decreased neuronal cell apoptosis. Added BP was converted stoichiometrically to the corresponding diphenoquinone indicating the synthetic anti-oxidant effectively decreased oxidative stress through a radical scavenging mechanism. Together, these data indicate that BP has the potential to act as a neuro-protective drug.
Alistair J. Gunn - One of the best experts on this subject based on the ideXlab platform.
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Effect of cerebral hypothermia and asphyxia on the subventricular zone and white matter tracts in preterm fetal sheep
Brain research, 2012Co-Authors: Robert D. Barrett, Laura Bennet, Justin M. Dean, Andrew S. Naylor, Sherly George, Alistair J. GunnAbstract:Abstract Prolonged, moderate cerebral hypothermia is consistently neuroprotective after Experimental Hypoxia–ischemia. We have previously shown that hypothermia is also protective after profound asphyxia in the preterm brain. However, there is a concern whether hypothermia could suppress the proliferative response to injury in the white matter or subventricular zone (SVZ). Preterm (0.7 gestation) fetal sheep received complete umbilical cord occlusion for 25 min followed by cerebral hypothermia (extradural temperature reduced from 39.4±0.3 to 29.5±2.6 °C) from 90 min to 70 h after the end of occlusion or sham cooling. Occlusion-normothermia was associated with no effect on CNPase+ cells, but loss of O4+ oligodendrocytes, induction of cleaved caspase-3, and IB4+ microglia in the gyral and periventricular white matter compared to sham-occlusion ( p p
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the effect of cerebral hypothermia on white and grey matter injury induced by severe Hypoxia in preterm fetal sheep
The Journal of Physiology, 2007Co-Authors: Laura Bennet, Justin M. Dean, Sherly George, Vincent Roelfsema, B S Emerald, Alistair J. GunnAbstract:Prolonged, moderate cerebral hypothermia is consistently neuroprotective after Experimental Hypoxia–ischaemia; however, it has not been tested in the preterm brain. Preterm (0.7 gestation) fetal sheep received complete umbilical cord occlusion for 25 min followed by cerebral hypothermia (fetal extradural temperature reduced from 39.4 ± 0.3 to 29.5 ± 2.6°C) from 90 min to 70 h after the end of occlusion or sham cooling. Occlusion led to severe acidosis and profound hypotension, which recovered rapidly after release of occlusion. After 3 days recovery the EEG spectral frequency, but not total intensity, was increased in the hypothermia-occlusion group compared with normothermia-occlusion. Hypothermia was associated with a significant overall reduction in loss of immature oligodendrocytes in the periventricular white matter (P < 0.001), and neuronal loss in the hippocampus and basal ganglia (P < 0.001), with suppression of activated caspase-3 and microglia (isolectin-B4 positive). Proliferation was significantly reduced in periventricular white matter after occlusion (P < 0.05), but not improved after hypothermia. In conclusion, delayed, prolonged head cooling after a profound hypoxic insult in the preterm fetus was associated with a significant reduction in loss of neurons and immature oligodendroglia, with evidence of EEG and haemodynamic improvement after 3 days recovery, but also with a persisting reduction in proliferation of cells in the periventricular region. Further studies are required to evaluate the long-term impact of cooling on brain growth and maturation.
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Differential effects of hypothermia on early and late epileptiform events after severe Hypoxia in preterm fetal sheep.
Journal of neurophysiology, 2006Co-Authors: Laura Bennet, Justin M. Dean, Guido Wassink, Alistair J. GunnAbstract:Moderate cerebral hypothermia is consistently neuroprotective after Experimental Hypoxia-ischemia; however, its mechanisms remain poorly defined. Using a model of complete umbilical cord occlusion ...
Ben S. Rayner - One of the best experts on this subject based on the ideXlab platform.
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protective effect of a synthetic anti oxidant on neuronal cell apoptosis resulting from Experimental Hypoxia re oxygenation injury
Journal of Neurochemistry, 2006Co-Authors: Ben S. Rayner, Simon J. Myers, T Hong T Duong, Paul K. WittingAbstract:Oxidative stress is associated with the pathology of acute and chronic neurodegenerative disease. Cultured neuronal cells exposed to Hypoxia-reoxygenation (H/R) injury, as a model for stroke, yield a burst of reactive oxygen species (ROS) as measured with electron paramagnetic resonance (EPR) spectroscopy in combination with spin trapping. Added superoxide dismutase inhibited spin-adduct formation verifying that superoxide radical anion was formed in neuronal cells following H/R injury. The intracellular ADP/ATP ratio increased rapidly over the first 5 h following injury and this was due primarily to the decreased cellular pools of ATP, consistent with the notion that H/R promotes mitochondrial dysfunction leading to decreased ATP reserve and increased ROS formation. As an early response to the enhanced oxidative stress, genes encoding for Hypoxia-inducible factor 1-alpha (HIF1-alpha), inducible haemoxygenase-1 (HO-1), and the oxygen-sensor neuroglobin increased significantly. Up-regulation of the HO-1 gene was paralleled by increased HO protein expression and activity. Despite this cellular response, apoptosis increased significantly following H/R injury indicating that the endogenous anti-oxidant defenses were unable to protect the cells. In contrast, addition of a phenolic anti-oxidant, bisphenol (BP), prior to H/R injury, inhibited ROS production and gene regulation and significantly decreased neuronal cell apoptosis. Added BP was converted stoichiometrically to the corresponding diphenoquinone indicating the synthetic anti-oxidant effectively decreased oxidative stress through a radical scavenging mechanism. Together, these data indicate that BP has the potential to act as a neuro-protective drug.
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Protective effect of a synthetic anti‐oxidant on neuronal cell apoptosis resulting from Experimental Hypoxia re‐oxygenation injury
Journal of neurochemistry, 2006Co-Authors: Ben S. Rayner, T. T. Hong Duong, Simon J. Myers, Paul K. WittingAbstract:Oxidative stress is associated with the pathology of acute and chronic neurodegenerative disease. Cultured neuronal cells exposed to Hypoxia-reoxygenation (H/R) injury, as a model for stroke, yield a burst of reactive oxygen species (ROS) as measured with electron paramagnetic resonance (EPR) spectroscopy in combination with spin trapping. Added superoxide dismutase inhibited spin-adduct formation verifying that superoxide radical anion was formed in neuronal cells following H/R injury. The intracellular ADP/ATP ratio increased rapidly over the first 5 h following injury and this was due primarily to the decreased cellular pools of ATP, consistent with the notion that H/R promotes mitochondrial dysfunction leading to decreased ATP reserve and increased ROS formation. As an early response to the enhanced oxidative stress, genes encoding for Hypoxia-inducible factor 1-alpha (HIF1-alpha), inducible haemoxygenase-1 (HO-1), and the oxygen-sensor neuroglobin increased significantly. Up-regulation of the HO-1 gene was paralleled by increased HO protein expression and activity. Despite this cellular response, apoptosis increased significantly following H/R injury indicating that the endogenous anti-oxidant defenses were unable to protect the cells. In contrast, addition of a phenolic anti-oxidant, bisphenol (BP), prior to H/R injury, inhibited ROS production and gene regulation and significantly decreased neuronal cell apoptosis. Added BP was converted stoichiometrically to the corresponding diphenoquinone indicating the synthetic anti-oxidant effectively decreased oxidative stress through a radical scavenging mechanism. Together, these data indicate that BP has the potential to act as a neuro-protective drug.
Somshuvra Mukhopadhyay - One of the best experts on this subject based on the ideXlab platform.
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Pulmonary arterial hypertension: a disease of tethers, SNAREs and SNAPs?
American journal of physiology. Heart and circulatory physiology, 2007Co-Authors: Pravin B. Sehgal, Somshuvra MukhopadhyayAbstract:Histological and electron microscopic studies over the past four decades have highlighted "plump," "enlarged" endothelial, smooth muscle, and fibroblastic cellular elements with increased endoplasmic reticulum, Golgi stacks, and vacuolation in pulmonary arterial lesions in human and in Experimental (Hypoxia and monocrotaline) pulmonary arterial hypertension. However, the contribution of disrupted intracellular membrane trafficking in the pathobiology of this disease has received insufficient attention. Recent studies suggest a pathogenetic role of the disruption of intracellular trafficking of vasorelevant proteins and cell-surface receptors in the development of this disease. The purpose of this essay is to highlight the molecular regulation of vesicular trafficking by membrane tethers, SNAREs and SNAPs, and to suggest how their dysfunction, directly and/or indirectly, might contribute to development of pulmonary arterial hypertension in Experimental models and in humans, including that due to mutations in bone morphogenetic receptor type 2.
June Bai - One of the best experts on this subject based on the ideXlab platform.
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Puerarin prevents progression of Experimental Hypoxia-induced pulmonary hypertension via inhibition of autophagy.
Journal of pharmacological sciences, 2019Co-Authors: Xiaodan Zhang, Qi Liu, Chen Zhang, Jie-jing Sheng, Xinying Yang, Xiaoying Wang, June BaiAbstract:Pulmonary arterial hypertension (PAH) is defined as elevation of mean pulmonary arterial pressure to ≥25 mmHg within the low pressure pulmonary circulatory system. PAH is characterized by obstructive vascular remodeling, partially due to excessive pulmonary arterial smooth muscle cell (PASMC) proliferation. Puerarin is a natural flavonoid isolated from the herb Radix puerariae, which has been widely used for the treatment of cardiovascular and cerebrovascular disorders and diabetes. However, how puerarin mediates autophagy in the progression of pulmonary vascular remodeling is unclear. In this study, we explored the effects of puerarin in a hypoxic pulmonary hypertension (PH) rat model using immunohistochemistry, and morphometric analyses of right ventricle. In addition, cell counting kit 8 assay, western blotting and flow cytometry were employed to test cell proliferation in PASMCs, and then autophagy was tested with mRFP-GFP-LC3 fluorescence microscopy and Western blot. We found that puerarin could alleviate Hypoxia-induced PH in rats and improved pulmonary histopathology, and also reduced the expression of autophagy markers in vivo and in vitro. Moreover, puerarin also ameliorated Hypoxia-induced PASMC proliferation in an autophagy-dependent manner. Overall, these findings demonstrated that puerarin could prevent Hypoxia-induced PH in rats, possibly via reducing autophagy and suppressing cell proliferation.
