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

This study was performed to evaluate whether cytokines, adhesion molecules, ghrelin and S-100B are useful markers in predicting the cerebral infarction after cardiac surgery with cardioplumomary bypass (CPB). The patients (n=20) were classified into two groups; group A (n=4) showed postoperative organized cerebral damage, while group B (n=16) consisted of patients without occurrence of postoperative strokes. Before CPB, serum levels of S-100B in both groups A and B were low (<0.5 ng/mL), while ghrelin concentrations in group A (all patients had history of strokes) were much higher than those in group B. After CPB, when serum levels of S-100B in group A at 24h were higher than those in group B, ghrelin in group A at same time point showed high levels in comparison to group B. At 12 and 24h after CPB, levels of tumor necrosis factor (TNF)-alpha, interleukin-10 and soluble TNF-receptor I in group A were significantly higher than those in group B. In conclusion, it is considered that ghrelin as well as S-100B can be a useful marker for the prediction of stoke after CPB. Increase of TNF-alpha, interleukin-10 and soluble TNF-receptor I after CPB may be involved in the pathogenesis of stroke after CPB.
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PMID:Relationship between cerebral injury and inflammatory responses in patients undergoing cardiac surgery with cardiopulmonary bypass. 1561 77

Cerebrovascular risk represents a progressive and evolving concept owing to the particular distribution of risk factors in patients with ischemic stroke and in light of the newest stroke subtype classifications that account for pathophysiological, instrumental, and clinical criteria. Age represents the strongest nonmodifiable risk factor associated with ischemic stroke, while hypertension constitutes the most important modifiable cerebrovascular risk factor, confirmed by a host of epidemiological data and by more recent intervention trials of primary (HOT, Syst-Eur, LIFE) and secondary (PROGRESS) prevention of stroke in hypertensive patients. To be sure, a curious relationship exists between stroke and diabetes. Although the Framingham Study, The Honolulu Heart Program, and a series of Finnish studies reported a linear relationship between improved glucose metabolism and cerebral ischemia, the clinical and prognostic profile of diabetic patients with ischemic stroke remains to be fully understood. Our group, on the basis of TOAST classification--a diagnostic classification of ischemic stroke developed in 1993 that distinguishes five different clinical subtypes of ischemic stroke: large-artery atherosclerosis (LAAS), cardioembolic infarct (CEI), lacunar infarct (LAC), stroke of other determined origin (ODE), and stroke of undetermined origin (UDE), and now extensively used in clinical and scientific context--analysed the prevalence of cerebrovascular risk factors and the distribution of TOAST subtypes in more 300 patients with acute ischemic stroke in two consecutives studies that reported the significant association between diabetes and the lacunar subtype and a better clinical outcome for diabetic patients, most likely related to the higher prevalence of the lacunar subtype. Well-confirmed are the roles of cigarette smoking, atrial fibrillation, and asymptomatic carotid stenosis as cerebrovascular risk factors. Particularly interesting seems to be the function of inflammation markers (CRP, TNF-alpha, IL-1 beta, ISPs) as potential risk factors. Still elusive remains the association between cholesterol serum levels and stroke, on the basis of the epidemiological data regarding this causative relationship, confirmed only by the results of intervention trials (4S, LIPID, CARE, HPS, ASCOT). Ultimately, cerebrovascular risk appears peculiar owing to the unique relationship between some modifiable risk factors (mainly diabetes and cholesterol) and the possible preferential association with stroke subtypes and specific cerebrovascular risks.
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PMID:Cerebrovascular risk factors and clinical classification of strokes. 1563 Jun 37

Owing to improving preventative, diagnostic, and therapeutic measures for cardiovascular disease and a variety of cancers, the average ages of North Americans and Europeans continue to rise. Regrettably, accompanying this increase in life span, there has been an increase in the number of individuals afflicted with age-related neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, and stroke. Although different cell types and brain areas are vulnerable among these, each disorder likely develops from activation of a common final cascade of biochemical and cellular events that eventually lead to neuronal dysfunction and death. In this regard, different triggers, including oxidative damage to DNA, the overactivation of glutamate receptors, and disruption of cellular calcium homeostasis, albeit initiated by different genetic and/or environmental factors, can instigate a cascade of intracellular events that induce apoptosis. To forestall the neurodegenerative process, we have chosen specific targets to inhibit that are at pivotal rate-limiting steps within the pathological cascade. Such targets include TNF-alpha, p53, and GLP-1 receptor. The cytokine TNF-alpha is elevated in Alzheimer's disease, Parkinson's disease, stroke, and amyotrophic lateral sclerosis. Its synthesis can be reduced via posttranscriptional mechanisms with novel analogues of the classic drug, thalidomide. The intracellular protein and transcription factor, p53, is activated by the Alzheimer's disease toxic peptide, Abeta, as well as by excess glutamate and hypoxia to trigger neural cell death. It is inactivated by novel tetrahydrobenzothiazole and -oxazole analogues to rescue cells from lethal insults. Stimulation of the glucagon-like peptide-1 receptor (GLP-1R) in brain is associated with neurotrophic functions that, additionally, can protect cells against excess glutamate and other toxic insults.
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PMID:New therapeutic strategies and drug candidates for neurodegenerative diseases: p53 and TNF-alpha inhibitors, and GLP-1 receptor agonists. 1568 14

Nearly half of the U.S. adult population is overweight or obese, which may be related to increased energy intake combined with lack of physical activity. Obesity increases the risk of several chronic diseases including diabetes, coronary heart disease, hypertension, and stroke. Conjugated linoleic acids (CLA) were shown to decrease fat and increase lean mass in several animal studies. However, the effects of CLA in combination with exercise (Ex) on body composition have not been studied in an animal model. We examined the effect of a low concentration of either safflower oil as control (0.5%) or mixed isomers of CLA (0.4%) along with treadmill exercise on body composition in male Balb/C mice fed a high-fat diet (20% corn oil) in a 2 x 2 factorial design. CLA consumption lowered change in fat mass (P < 0.001) confirming the results of other studies, and change in fat mass decreased further (P < 0.001) with CLA and exercise. Change in lean mass did not increase with exercise alone; it increased, although not significantly, with CLA alone and increased significantly (P < 0.05) due to the combination of CLA and exercise. This effect was accompanied by decreased serum leptin levels and lower leptin mRNA expression in peritoneal fat (P < 0.001). Serum insulin, glucose, tumor necrosis factor (TNF)-alpha, and interleukin-6 were lower in CLA-fed mice than in controls (P < 0.05), whereas serum TNF-alpha was increased by exercise (P < 0.05). Exercise increased oxygen consumption and energy expenditure when measured under resting conditions (P < 0.05). In summary, the combination of dietary CLA and exercise decreased fat mass and increased lean mass in mice fed a high-fat diet, and these effects may be related in part to decreased serum leptin and exercise-induced increases in oxygen consumption and energy expenditure.
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PMID:The combination of dietary conjugated linoleic acid and treadmill exercise lowers gain in body fat mass and enhances lean body mass in high fat-fed male Balb/C mice. 1586 92

Central nervous system (CNS) ischaemia is associated with an acute inflammatory response which appears to potentiate CNS injury, especially following reperfusion. This response includes the release of inflammatory mediators, including the cytokines interleukin-1 (IL-1) and TNF-alpha. These trigger the production of additional cytokines, including IL-6, and activate leukocytes which infiltrate the CNS. IL-6 appears to play a central role in modulating this response, exhibiting both pro-inflammatory and anti-inflammatory activities. Preliminary clinical studies suggest that plasma levels of IL-6 are correlated with stroke size and functional recovery. Conversely, brain levels of cytokines have been demonstrated to increase following experimental ischaemia. Although there are at present no clinical ;anti-cytokine' treatment studies, experimental studies modulating cytokines have shown neuroprotection.
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PMID:The therapeutic potential of anti-cytokine strategies in central nervous system ischaemia. 1598 8

Patients with type 2 diabetes mellitus (NIDDM) are at risk for macrovascular disease complications, such as myocardial infarction (MI) or stroke from plaque rupture. Cytokines play a key role in plaque vulnerability. IFN-gamma inhibits collagen synthesis thereby affecting plaque stability. High IL-6, TNF-alpha, and dyslipidemia are risk factors for thrombosis. Abnormal increments of HSP70 in atherosclerotic plaques might lead to plaque instability and rupture caused by chronic inflammation, which up-regulates the expression of pro-inflammatory cytokines (IL-6 and TNF-alpha) in human monocytes. Studies of a polymorphic PstI site lying in the coding region at position 1267 of the HSP70-2 gene have shown that the BB genotype is associated with NIDDM. We screened 60 old NIDDM patients with carotid stenosis and 107 old healthy controls for 1267 HSP70-2 polymorphism in order to establish if an association with plaque frailty exists. Different genotypic distributions were observed between patients and healthy controls. An increased relative risk was associated with the B allele (p = 0.0107; odds ratio = 1.861). HSP70-2, IL-6, IFN-gamma, TNF-alpha gene expressions within the plaques and serum levels of triglyceride, total cholesterol and LDL cholesterol were tested from patients stratified according to their B+ (AB and BB) and B- (AA) genotypes. Plaque morphology (soft or fibrous-calcified) and the incidence of cerebral ischaemia were also assessed. B+ patients showed increased HSP70-2, IL-6, IFN-gamma, TNF-alpha and dyslipidemia as compared to B- carriers. The frequency of soft plaques increased in B+ in comparison to B- patients (67% versus 13%; odds ratio 13.0, p = 0.0006). A higher frequency of cerebral ischaemia (ictus or transient ischaemic attack (TIA)) was present in B+ than in B- genotype (53% versus 20%; odds ratio 4.57, p < 0.05) Hence, 1267 HSP70-2 polymorphism may be of use in identifying B+ NIDDM patients at risk for carotid plaque rupture and cerebral ischaemia.
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PMID:1267 HSP70-2 polymorphism as a risk factor for carotid plaque rupture and cerebral ischaemia in old type 2 diabetes-atherosclerotic patients. 1599 11

Atherosclerosis is a complex disease involved in major fatal events such as myocardial infarction and stroke. It is the result of interactions between metabolic, dietetic and environmental risk factors acting on a genetic background that could result in endothelial susceptibility. Our aim was to determine the patterns of expression of adhesion molecules and whether phosphatidylserine is translocated to the cell surface of human umbilical vein endothelial cells (HUVECs) isolated from healthy newborns born to parents with a strong family history of myocardial infarction under TNF-alpha or oxLDL stimulated conditions. Compared to control HUVECs, experimental cords showed: (a) a four-fold increase in VCAM-1 expression under basal conditions, which showed no change after stimulation with the pro-atherogenic factors; (b) a two-fold increase in basal P-selectin expression that reached a 10-fold increase with any of the pro-atherogenic factors; (c) a basal ICAM-1 expression similar to P-selectin that was not modified by the pro-atherogenic molecules; (d) a similar PECAM-1 expression. Unexpectedly, phospathidylserine expression in experimental cord HUVECs was significantly increased (211 817 versus 3354 TFU) but was not associated to apoptotic death as the percentage of dead cells induced by TNF-alpha treatment was very low (0.55 versus 9.87% in control HUVECs). The latter result was corroborated by TUNEL staining. T cell adherence to HUVECs was highly up-regulated in the genetically predisposed samples. The analysis of nonpooled HUVECs, from newborns to family predisposed myocardial-infarction individuals, might represent a useful strategy to identify phenotypical and functional alterations, and hopefully, to take early preventive actions.
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PMID:HUVECs from newborns with a strong family history of myocardial infarction overexpress adhesion molecules and react abnormally to stimulating agents. 1604 34

Clinical experimental stroke induces injurious local brain inflammation. However, effects on the peripheral immune system have not been well characterized. We quantified mRNA and protein levels for cytokines, chemokines, and chemokine receptors (CCR) in brain, spinal cord, peripheral lymphoid organs (spleen, lymph node, blood, and cultured mononuclear cells from these sources), and blood plasma after reversible middle cerebral artery occlusion (MCAO) or sham treatment in male C57BL/6 mice. Middle cerebral artery occlusion induced a complex, but organ specific, pattern of inflammatory factors in the periphery. At both 6 and 22 h after MCAO, activated spleen cells from stroke-injured mice secreted significantly enhanced levels of TNF-alpha, IFN-gamma, IL-6, MCP-1, and IL-2. Unstimulated splenocytes expressed increased chemokines and CCR, including MIP-2 and CCR2, CCR7 and CCR8 at 6 h; and MIP-2, IP-10, and CCR1 and CCR2 at 22 h. Also at 22 h, T cells from blood and lymph nodes secreted increased levels of inflammatory cytokines after activation. As expected, there were striking proinflammatory changes in postischemic brain. In contrast, spinal cord displayed suppression of all mediators, suggesting a compensatory response to intracranial events. These data show for the first time that focal cerebral ischemia results in dynamic and widespread activation of inflammatory cytokines, chemokines, and CCR in the peripheral immune system.
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PMID:Experimental stroke induces massive, rapid activation of the peripheral immune system. 1612 Nov 26

Expression of TNF-alpha, a pleiotropic cytokine, is elevated during stroke and cerebral ischemia. TNF-alpha regulates arterial diameter, although mechanisms mediating this effect are unclear. In the present study, we tested the hypothesis that TNF-alpha regulates the diameter of resistance-sized ( approximately 150-microm diameter) cerebral arteries by modulating local and global intracellular Ca(2+) signals in smooth muscle cells. Laser-scanning confocal imaging revealed that TNF-alpha increased Ca(2+) spark and Ca(2+) wave frequency but reduced global intracellular Ca(2+) concentration ([Ca(2+)](i)) in smooth muscle cells of intact arteries. TNF-alpha elevated reactive oxygen species (ROS) in smooth muscle cells of intact arteries, and this increase was prevented by apocynin or diphenyleneiodonium (DPI), both of which are NAD(P)H oxidase blockers, but was unaffected by inhibitors of other ROS-generating enzymes. In voltage-clamped (-40 mV) cells, TNF-alpha increased the frequency and amplitude of Ca(2+) spark-induced, large-conductance, Ca(2+)-activated K(+) (K(Ca)) channel transients approximately 1.7- and approximately 1.4-fold, respectively. TNF-alpha-induced transient K(Ca) current activation was reversed by apocynin or by Mn(III)tetrakis(1-methyl-4-pyridyl)porphyrin (MnTMPyP), a membrane-permeant antioxidant, and was prevented by intracellular dialysis of catalase. TNF-alpha induced reversible and similar amplitude dilations in either endothelium-intact or endothelium-denuded pressurized (60 mmHg) cerebral arteries. MnTMPyP, thapsigargin, a sarcoplasmic reticulum Ca(2+)-ATPase blocker that inhibits Ca(2+) sparks, and iberiotoxin, a K(Ca) channel blocker, reduced TNF-alpha-induced vasodilations to between 15 and 33% of control. In summary, our data indicate that TNF-alpha activates NAD(P)H oxidase, resulting in an increase in intracellular H(2)O(2) that stimulates Ca(2+) sparks and transient K(Ca) currents, leading to a reduction in global [Ca(2+)](i), and vasodilation.
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PMID:TNF-alpha dilates cerebral arteries via NAD(P)H oxidase-dependent Ca2+ spark activation. 1653 72

The role of genetic factors in the individual predisposition to develop ischemic stroke has been assessed by previous studies performed both in animal models and in humans. The main goal of the current investigation was to determine the possible contribution of genes encoding procoagulant and inflammatory factors on the occurrence of ischemic stroke in a cohort of young cases and corresponding controls. One hundred and fifteen cases of ischemic stroke were recruited for this study. A detailed clinical assessment, a definite etiologic diagnosis, as well as the presence/absence of known risk factors for ischemic stroke were obtained for each patient. As a control group 180 healthy, unrelated subjects were included. The whole population was screened for polymorphisms belonging to genes encoding FII, FV, alpha-fibrinogen, beta-fibrinogen, GP IIb/IIIa, tumor necrosis factor (TNF)-alpha, interleukin 1-beta. Hypertension was the most important risk factor for ischemic stroke in our cohort [OR = 6.9, confidence interval (CI) 2.9-16.7, P < 0.0001]. Among all genes tested, the TNF-alpha gene variant exerted a significant, independent effect on individual predisposition to ischemic stroke occurrence (OR = 1.8, CI = 1.01-3.3, P < 0.05). Our findings, obtained in a cohort of young Italian patients, may support the existence of a direct contributory role of TNF-alpha, a proinflammatory cytokine protein, in the susceptibility to brain damage.
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PMID:A role of TNF-alpha gene variant on juvenile ischemic stroke: a case-control study. 1632 93


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