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

The expression of 70 kDa heat shock protein (HSP-70) in focal ischemia occurs in regions that sustain sub-lethal ischemic injury, and may therefore be considered as a biological marker of the ischemic penumbra. In a rat embolic stroke model, using fibrin-rich emboli, we correlated the expression of HSP-70 mRNA with diffusion magnetic resonance imaging (MRI) to determine if HSP-70 mRNA expression was associated with alterations in the apparent diffusion coefficient (ADC) of brain tissue water, a putative early marker of cytotoxic injury that is readily measured in vivo. Serial ADC measurements were made for 120 min following embolic infarction in the right carotid artery territory. HSP-70 mRNA expression was observed at the boundaries of the densely ischemic zone, as judged by diffusion imaging. ADC values observed in HSP-70 mRNA-positive regions were intermediate between those observed in the ischemic core or in control regions. In addition, the volume of HSP-70 mRNA-positive tissue correlated positively with the volume of tissue showing intermediate ADC values at 120 min. These findings suggest that intermediate ADC values occur in penumbral regions. Heterogeneity of ischemic cellular injury is suggested as the basis for the intermediate ADC values observed in these regions.
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PMID:Correlation of diffusion MRI and heat shock protein in a rat embolic stroke model. 912 12

Stroke, an age-related disorder involving degeneration of neurons resulting from cerebral ischemia, is a major cause of disability and mortality. Although dietary restriction (DR) extends lifespan and reduces levels of cellular oxidative stress in several different organ systems including the brain, the impact of DR on ischemic brain injury is unknown. We report that maintenance of adult rats on a DR regimen resulted in reduced brain damage and improved behavioral outcome in a middle cerebral artery occlusion-reperfusion (MCAO-R) stroke model. Administration of 2-deoxyglucose (2-DG), a nonmetabolizable analogue of glucose, to rats fed ad libitum resulted in reduced ischemic brain damage and improved behavioral outcome following MCAO-R. 2-DG protected cultured hippocampal neurons against chemical hypoxia, demonstrating a direct protective action on neurons. DR and 2-DG administration resulted in an increase in the level of the stress protein heat-shock protein 70 (HSP-70) in striatal cells in vivo, and 2-DG treatment induced HSP-70 in cultured neurons suggesting involvement of a preconditioning stress response in the neuroprotective actions of DR and 2-DG. The neuroprotective effect of DR and 2-DG in this focal cerebral ischemia model suggests that outcome following stroke may be improved in individuals who follow a regimen of reduced food intake.
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PMID:Dietary restriction and 2-deoxyglucose administration reduce focal ischemic brain damage and improve behavioral outcome: evidence for a preconditioning mechanism. 1046 54

Recent studies have shown that rats and mice maintained on a dietary restriction (DR) regimen exhibit increased resistance of neurons to excitotoxic, oxidative, and metabolic insults in experimental models of Alzheimer's, Parkinson's, and Huntington's diseases and stroke. Because synaptic terminals are sites where the neurodegenerative process may begin in such neurodegenerative disorders, we determined the effects of DR on synaptic homeostasis and vulnerability to oxidative and metabolic insults. Basal levels of glucose uptake were similar in cerebral cortical synaptosomes from rats maintained on DR for 3 months compared with synaptosomes from rats fed ad libitum. Exposure of synaptosomes to oxidative insults (amyloid beta-peptide and Fe(2+)) and a metabolic insult (the mitochondrial toxin 3-nitropropionic acid) resulted in decreased levels of glucose uptake. Impairment of glucose uptake following oxidative and metabolic insults was significantly attenuated in synaptosomes from rats maintained on DR. DR was also effective in protecting synaptosomes against oxidative and metabolic impairment of glutamate uptake. Loss of mitochondrial function caused by oxidative and metabolic insults, as indicated by increased levels of reactive oxygen species and decreased transmembrane potential, was significantly attenuated in synaptosomes from rats maintained on DR. Levels of the stress proteins HSP-70 and GRP-78 were increased in synaptosomes from DR rats, consistent with previous data suggesting that the neuroprotective mechanism of DR involves a "preconditioning" effect. Collectively, our data provide the first evidence that DR can alter synaptic homeostasis in a manner that enhances the ability of synapses to withstand adversity.
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PMID:Beneficial effects of dietary restriction on cerebral cortical synaptic terminals: preservation of glucose and glutamate transport and mitochondrial function after exposure to amyloid beta-peptide, iron, and 3-nitropropionic acid. 1085 76

Review of results of experimental and clinical studies indicates that the penumbra of physiologically impaired but potentially salvageable tissue surrounding the central core of focal cerebral ischemia that develops shortly after onset of major conducting vessel occlusion is complex and dynamic with severity and duration thresholds for hypoxic stress and injury that are specific to tissue site, cell type, molecular pathway or gene expression investigated and efficiency of collateral or residual flow and reperfusion. Imaging methods that have been utilized in vivo to identify penumbra and predict response to reperfusion and other protective therapies include magnetic resonance spectroscopy, diffusion- and perfusion-MRI as well as positron emission tomography. However, resolution of focal lesions characterized by lactic acidosis or cellular edema does not predict tissue survival, and imaging thresholds for resuscitation after reperfusion have not been determined experimentally. HSP-70 stress protein induction represents an endogenous protective mechanism that occurs in penumbra but not core neurones. A robust protective effect has been demonstrated during focal ischemia in transgenic mice overexpressing HSP-70 perhaps by suppressing early cytochrome c release. Delayed manganese mediated striatal neurodegeneration can be detected with T1 MRI after brief episodes of transient focal ischemia. Future studies may define endogenous cytotoxic and cytoprotective molecular penumbras that can be exploited to improve outcome after temporary focal ischemia.
Stroke 2004 Nov
PMID:Molecular identification of the ischemic penumbra. 1548 32

This study tested the application of an immunoisotopic assay for immunohistochemical localization and quantification of proteins in brain sections from rats without or with transient focal ischemia. We assessed the hypothesis that measurements of protein levels in injured brain determined by an isotopic assay using [(125)I]-protein A have greater reliability than those made by conventional immunoperoxidase labeling using diaminobenzidine. Quantification of immunoreactivities for glial fibrillary acidic protein (GFAP), glutamate transporter-1 (GLT-1) and heat shock protein-70 (HSP-70) was determined by optical density signal in the immunoisotopic and immunoperoxidase assays. In ischemic brain, the immunoisotopic assay detected protein increases (cortical penumbra HSP-70, 151+/-6%), protein decreases (cortical ischemic core GLT-1, 61+/-6%) and no changes in GFAP levels compared to controls animals. These results differed from the protein levels found by the immunoperoxidase assay, which showed elevated HSP-70, GLT-1 and GFAP in all ischemic regions. We conclude that nonspecific immunosignal confounds assessments of protein expression in injured brain and that the immunoisotopic method is a valid approach to regionally localize and quantify proteins after brain injury. The disadvantage of the falsely positive overestimation of protein immunoreactivity after stroke with the immunoperoxidase method has to be weighted with the advantage of the cellular resolution.
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PMID:In situ immunoradiographic method for quantification of specific proteins in normal and ischemic brain regions. 1581 55

Atherosclerosis, and the resulting coronary heart disease and stroke, is the most common cause of death in developed countries. Atherosclerosis is an inflammatory process that results in the development of complex lesions or plaques that protrude into the arterial lumen. Plaque rupture and thrombosis result in the acute clinical complications of myocardial infarction (MI) and stroke. Although certain risk factors (dyslipidemias, diabetes, hypertension) and humoral markers of plaque vulnerability (C-reactive protein, interleukin-6, 10 and 18, CD40L) have been identified, a highly sensitive and specific biomarker or protein profile, which could provide information on the stability/vulnerability of atherosclerotic lesions, remains to be identified. In this review, we report several proteomic approaches which have been applied to circulating or resident cells, atherosclerotic plaques or plasma, in the search for new proteins that could be used as cardiovascular biomarkers. First, an example using a differential proteomic approach (2-DE and MS) comparing the secretome from control mammary arteries and atherosclerotic plaques is displayed. Among the different proteins identified, we showed that low levels of HSP-27 could be a potential marker of atherosclerosis. Second, we have revised several studies performed in cells involved in the pathogenesis of atherosclerosis (foam cells and smooth muscle cells). Another approach consists of performing proteomic analysis on circulating cells or plasma, which will provide a global view of the whole body response to atherosclerotic aggression. Circulating cells can bear information reflecting directly an inflammatory or pro-coagulant state related to the pathology. As an illustration, we report that circulating monocytes and plasma in patients with acute coronary syndromes has disclosed that mature Cathepsin D is increased both in the plasma and monocytes of these patients. Finally, the problems of applying proteomic approach directly to plasma will be discussed. The purpose of this review is to provide the reader with an overview of different proteomic approaches that can be used to identify new biomarkers in vascular diseases.
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PMID:Quest for novel cardiovascular biomarkers by proteomic analysis. 1608 68

Atherosclerosis (AT) is a metabolic, systemic inflammatory/immune disease characterized by lipoproteins metabolism alteration that leads to immune/inflammatory system activation with the consequent proliferation of smooth-muscle cells, narrowing arteries and atheroma formation. Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombophilic state and circulating antiphospholipid antibodies (aPL) including anti beta2-GPI. Experimental studies and human observations suggest that APS is associated with AT. In fact, innate and adaptive immune responses participate in the pathogenesis of both diseases. Anti-oxLDL, anti-aPL, anti beta2GPI, anti-HSP antibodies, among others, has been found in patients with APS and AT. Endothelial dysfunctions, oxidative stress, increase of cell adhesion molecules, active platelets, are common findings in both diseases. Macrophages, dendritic cells, T-cell activation, CD40-CD40 ligand interaction, are considered as pathogenic mechanism of AT and APS. Premature AT may be the first symptom of APS. Thrombophilia, aPL antibodies, and APS may be present in patients with premature AT. An association between AT and venous thrombosis (a clinical hallmark of APS) has been proposed in unselected patients with deep venous thrombosis of the legs without symptomatic AT. Asymptomatic AT, defined in terms of carotid intima media thickness and lumen diameter decrease, was observed in patients with APS. Premenopausal female patients with PAPS have a higher prevalence of cerebrovascular disease in comparison with male patients. Accelerated AT and hormones could be the explanation of these findings. High levels of aCLs, significantly predict the risk of future ischemic stroke in women but not in men. AT is one of the main features of systemic APS and offer opportunities for new treatment strategies.
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PMID:Systemic antiphospholipid syndrome and atherosclerosis. 1791 89

Myocardial infarction and stroke are exaggerated by rupture of atherosclerotic lesions. Rupture-sensitive plaques have a specific composition which renders them vulnerable, but additional factors (acute infection, higher sympathetic activity, excessive increase of blood pressure or exposure to a variety of drugs) are needed to set off the event. Toll-like receptors are important components of the innate and adaptive immune system and seem to be a potential link between inflammation, infectious disease and atherosclerosis. In addition to classical bacterial and viral antigens, several endogenous ligands (HSP, ox-LDL, apoptotic cells) have also been proposed to react to TLRs. There is accumulating evidence substantiating the contribution of the TLR-signaling pathway not only in the initiation but also in the progression of atherosclerosis. TLRs also play a key role in the development of tissue ischemia. Apoptosis and inflammation comprise two important indicators of plaque instability, and trigger factors augmenting rapidly TLR signaling can lead to aggravation of plaque-rupture. Due to their multiplex involvement in ischemic conditions, Toll-like receptors may be a promising target for therapeutic intervention. In situations such as acute coronary syndrome, in which inhibition of the inflammatory cascade is warranted, the administration of TLR-blocking agents as adjuvant therapy and the clinical usefulness of this association should be considered.
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PMID:Toll-like receptors: link between "danger" ligands and plaque instability. 1951 53

Exercise preconditioning induces neuroprotection after stroke. We investigated the beneficial role of heat shock protein-70 (HSP-70) and phosphorylated extracellular-signal-regulated-kinase 1/2 (pERK 1/2), as they pertain to reducing apoptosis and their influence on Bcl-x(L), Bax, and apoptosis-inducing factor (AIF) in rats subjected to ischemia and reperfusion. Adult male Sprague-Dawley rats were subjected to 30 min of exercise on a treadmill for 1, 2, or 3 weeks. Stroke was induced by a 2-h middle cerebral artery (MCA) occlusion using an intraluminal filament. Protein levels of HSP-70, pERK 1/2, Bcl-x(L), Bax, and AIF were analyzed using Western blot. Neuroprotection was based on levels of apoptosis (TUNEL) and infarct volume (Nissl staining). Immunocytochemistry was used for cellular expression of HSP-70 and pERK 1/2. Significant (P<0.05) up-regulation of HSP-70 and pERK 1/2 after 3 weeks of exercise coincided with significant (P<0.05) reduction in neuronal apoptosis and brain infarct volume. Inhibition of either one of these two factors showed a significant (P<0.05) reversal in the neuroprotection. Bax and AIF were down-regulated, while levels of Bcl-x(L) were up-regulated in response to stroke after exercise. Inhibiting HSP-70 or pERK 1/2 reversed this resultant increase or decrease. Our results indicate that exercise diminishes neuronal injury in stroke by up-regulating HSP-70 and ERK 1/2.
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PMID:Exercise preconditioning reduces neuronal apoptosis in stroke by up-regulating heat shock protein-70 (heat shock protein-72) and extracellular-signal-regulated-kinase 1/2. 2008 67

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 2h following focal stroke in rats, and remained elevated for one week. Therefore, we hypothesized that Guo could be a potential candidate for a non-toxic neuroprotective agent. In the present study, we examined the effects of Guo on rats following permanent middle cerebral artery occlusion (MCAO). We also determined whether Guo can precondition neurons by modulating endoplasmic reticulum (ER) stress proteins. As most therapies employ a combination treatment regimen, we optimized the neuroprotection by combining pre- and post-MCAO treatments with Guo, attempting to reduce both ischemic cell death and improve functional recovery. A combination of 4mg/kg Guo given 30min pre-stroke and 8mg/kg Guo given 3, 24 and 48h post-stroke exerted the most significant decrease in infarct volume and sustainable improvement in neurological function. Moreover, these effects are not attributable to Guo metabolites. Measurements taken 6h post-MCAO from animals pre-treated with Guo did not reveal any significant changes in ER stress proteins (GRP 78 and 94) or HSP 70, but did reveal significantly increased levels of m-calpain. Thus, our data indicate that there is a treatment regimen for Guo as a neuroprotectant following ischemic stroke. The mechanism by which Guo confers neuroprotection may involve an increase in m-calpain, possibly resulting from a mild increase in intracellular calcium. M-calpain may be involved in the preconditioning response to ischemia by upregulating endogenous pro-survival mechanisms in neurons.
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PMID:Systemic administration of guanosine promotes functional and histological improvement following an ischemic stroke in rats. 2177 19


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