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Edaravone, an electron spin trapper with radical scavenging activity, has been shown to be effective in reducing infarct volume in humans following ischemic stroke. However, concerns of edaravone-induced renal toxicity have limited its clinical adoption. Previous work has demonstrated that edaravone...
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The present study demonstrates the benefits of combinatorial antioxidant therapy in the treatment of ischemic stroke. Male Sprague-Dawley rats were anaesthetised and the middle cerebral artery (MCA) was occluded for 30 minutes followed by 5.5 hours of reperfusion. Pretreatment with resveratrol 30 mi...
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OBJECTIVE: To investigate the anti-inflammatory, anti-oxidative stress, and adipokine-ameliorating effects of Liuwei Dihuang (LWDH), a traditional Chinese herbal formula, in obese rats. METHODS: After 2 weeks of acclimation with free access to regular rodent chow and water, obese-prone-caesarean-...
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The pregnancy hormone relaxin protects tissue from ischemic damage. The ability of relaxin-3, a relaxin paralog, to do so has not been explored. The cerebral expression of these peptides and their receptors make them logical targets for study in the ischemic brain. We assessed relaxin peptide-mediat...
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The present application relates to novel apocynin-lopioc acid covalent conjugates, compositions comprising these compounds and their use, in particular for the treatment of diseases, disorders or conditions that are mediated by oxidative stress. In particular, the present application includes compou...
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Resveratrol, a dietary polyphenol with antioxidant and anti-inflammatory activity, has been shown to provide neuroprotection in models of ischemia. However, the mechanism of action of resveratrol-induced neuroprotection remains unclear. Previous work in our laboratory has provided evidence that acut...
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Obesity has become an increasingly common health condition over the last several decades. It has been estimated that this largely preventable disease affects over one billion people worldwide and that its prevalence will have doubled by the year 2030. Currently, obesity is the leading cause of preve...
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The present study was aimed at investigating the efficacy and mechanism(s) of action of a Chinese herbal formulation, Liuwei Dihuang (LWDH), as a prospective natural weight-lowering product. Following a 2-week acclimation period, 48 obesity-prone (OP-CD) rats were divided into 4 groups (n=12 each). ...
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After ischemic stroke, early thrombolytic therapy to reestablish tissue perfusion improves outcome but triggers a cascade of deleterious cellular and molecular events. Using a collaborative approach, our groups examined the effects of guanosine (Guo) in response to ischemic reperfusion injury in vit...
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Apocynin is a well-known NADPH-oxidase inhibitor currently being investigated for its potential therapeutic use in patients with cardiovascular disease, such as occlusive stroke. However, the use of apocynin as a potential neuroprotective agent has come under criticism due to a narrow experimental t...
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Background. Lipoic acid (LA), which has significant antioxidant properties, may also function as a potent neuroprotectant. The synthetic compounds INV-155, INV-157, INV-159, and INV-161 are physiochemical combinations of lipoic acid and captopril. We sought to determine if these compounds have neuro...
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Previous work in our laboratory has provided evidence that preadministration of apocynin and lipoic acid at subthreshold levels for neuroprotection enhanced the neuroprotective capacity when injected in combination. Therefore, the present investigation wa...
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Substance P (SP) and cocaine employ similar mechanisms to modify excitatory synaptic transmission in the nucleus accumbens (NAc), a region implicated in substance abuse. Here we explored, using NAc slices, whether SP effects on these synaptic responses were altered in rats that have been sensitized ...
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Abstract:  Genetic polymorphisms in enzymes controlling the formation and disposition of estrogens and their metabolites have been shown to influence breast cancer risk. Environmental and lifestyle factors may interact with estrogen metabolism polymorphisms to influence breast cancer risk. We...
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Lipoic acid (LA) is a naturally occurring compound and dietary supplement with powerful antioxidant properties. Although LA is neuroprotective in models of stroke, little is known about the cellular mechanisms by which it confers protection during the early stages of ischemia. Here, using a rat mode...
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In the present study, we tested the hypothesis that selective activation of estrogen receptor subtypes (ERalpha and ERbeta) would be neuroprotective following ischemia and/or ischemia-reperfusion, as well as prevent the associated autonomic dysfunction. The selective ERalpha agonist, PPT, when admin...
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Previously we have found that extracellular guanosine (Guo) has neuroprotective properties in in vitro and in vivo. Moreover, extracellular Guo significantly increased in the ipsilateral hemisphere within 2 h following focal stroke in rats, and remained elevated for one week. Therefore, we hypothes...
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The present study was designed to determine a dose-response relationship between apocynin and infarct volume as well as to provide a possible molecular mechanism mediating this effect. We tested the hypothesis that apocynin protects against cell death following stroke and reperfusion injury. Apocyni...
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Current in vitro models of stroke involve applying oxygen-glucose deprived (OGD) media over an entire brain slice or plate of cultured neurons. Thus, these models fail to mimic the focal nature of stroke as observed clinically and with in vivo rodent models of stroke. Our aim was to develop a novel ...
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We have developed a novel rodent animal model of reperfusion injury following stroke. In this model, blood flow through the middle cerebral artery (MCA) is temporarily occluded by placing gentle pressure on sutures behind the artery along three separate branches. The sutures remain in place for a pe...
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We tested the hypothesis that Substance P (SP) produces the same effects as cocaine by examining their actions on excitatory synaptic transmission in the nucleus accumbens (NAc). SP produced an irreversible depression of non-NMDA receptor mediated EPSC: EC50:0.12 uM; maximal suppression: −33.4 ± ...
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Mild NMDA receptor activation is correlated with neuroprotection in models of cerebral ischemia. Neuroprotection with NMDA manifests as a form of ischemic tolerance and involves the induction of cellular stress systems sensitive to disturbances in cellular calcium homeostasis. Unilateral micro-injec...
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Ischemic tolerance describes a phenomenon whereby subcritical stimuli evoke cellular protective mechanisms resulting in increased tolerance to subsequent ischemia. In the present study we propose that the cytoprotective effects attributed to 17β-estradiol and tunicamycin in an in vivo rodent model ...