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

Tumor necrosis factor-alpha (TNF alpha) has been implicated as an endogenous mediator of the cardiovascular manifestations of sepsis and septic shock. We studied the acute effects of a single dose (50 or 200 micrograms/kg) of intravenous recombinant human TNF alpha (rhTNF alpha) on myocardial function in halothane-anesthetized dogs. Regional cardiac dimensions were measured by using sonomicrometry. Intracavitary left ventricular, ascending aortic, and pulmonary artery pressures were measured by use of micromanometers. Cardiac index was determined by means of thermodilution. Myocardial performance was analyzed by assessing changes in the slope of the left ventricular end-diastolic length-stroke work relationship obtained by performing transient vena caval occlusions. Animals were resuscitated by means of normal saline solutions to maintain baseline regional end-diastolic length. Over a 3-hour period of observation, rhTNF alpha decreased systemic vascular resistance index, but the cytokine did not compromise intrinsic myocardial performance. The circulatory response to rhTNF alpha was a hyperdynamic state characterized by tachycardia, augmented cardiac index, and increased intrinsic myocardial contractility (leftward shift of the left ventricular end-diastolic length-stroke work relationship). In addition, rhTNF alpha caused systemic acidosis and increased plasma levels of prostacyclin metabolite (6-keto-prostaglandin F1 alpha). After the dose of rhTNF alpha large volumes of fluid were required to maintain baseline end-diastolic length. We conclude that in the acute setting, rhTNF alpha elicits abnormalities in peripheral vascular tone that are not accompanied by depression of myocardial function.
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PMID:Load-insensitive assessment of myocardial performance after tumor necrosis factor-alpha in dogs. 159 65

We used a load-insensitive index of systolic left ventricular (LV) function and an analysis of diastolic pressure-dimension relationships to test the hypothesis that recombinant human (rh) tumor necrosis factor-alpha (TNF alpha) impairs LV function in dogs. Animals were studied 7-10 d after aseptic implantation of instrumentation to monitor cardiac output, external anterior-posterior LV diameter, and LV and pleural pressures. Data were analyzed from seven dogs that received active rhTNF alpha (100 micrograms/kg over 60 min) and from five dogs that received heat-inactivated rhTNF alpha. At 24 h after infusion of active rhTNF alpha, the slope of the LV end-diastolic dimension-stroke work relationship decreased significantly, indicating a decrement in LV systolic contractility. Simultaneously, LV unstressed dimension increased significantly, suggesting diastolic myocardial creep. The end-diastolic relationship between LV transmural pressure and normalized LV dimension (strain) was markedly displaced to the left, suggesting increased diastolic elastic stiffness. Despite these changes in LV performance, cardiac index was maintained by tachycardia. The abnormalities in LV function were resolved by 72 h. We conclude that rhTNF alpha reversibly impairs LV systolic and diastolic function in unanesthetized dogs. Because dysfunction occurs greater than 6 h after the infusion of rhTNF alpha and persists for 24-48 h, the mechanism underlying this phenomenon may involve secondary mediators or a change in myocardial gene expression.
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PMID:Left ventricular systolic and diastolic dysfunction after infusion of tumor necrosis factor-alpha in conscious dogs. 164 12

Rats produced more TNF activity in cerebrospinal fluid (CSF) than in blood after intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). After intravenous (i.v.) LPS, blood TNF levels exceeded CSF levels. Thus, brain cells appear to produce TNF in response to LPS. Rats with the stroke-risk factors hypertension or combined hypertension and genetic stroke-proneness produce more TNF in response to a provocative dose of LPS i.v. than control animals free of these risk factors. The possible relevance to stroke vulnerability is discussed.
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PMID:Lipopolysaccharide-induced production of tumor necrosis factor activity in rats with and without risk factors for stroke. 202 11

There is evidence that leukocytes play an important role in mediating tissue injury during acute ischemic stroke. Endothelial cell adhesive molecules such as ICAM-1 are required for the migration of leukocytes into the brain. Using an Elisa, we compared the expression of ICAM-1 by human brain microvascular endothelial cells with human umbilical vein endothelial cells. There was constitutive surface expression of ICAM-1 on both brain and umbilical vein endothelial cells. With cytokine (IL-1 beta or TNF) or lipopolysaccaride stimulation, ICAM-1 surface expression increased to a greater extent on brain than on umbilical vein endothelial cells. Dexamethasone at doses up to 100 microM had no effect on inhibiting cytokine-mediated upregulation of ICAM-1 on human brain microvascular endothelial cells.
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PMID:ICAM-1 expression on human brain microvascular endothelial cells. 791 16

Lipopolysaccharide (LPS)-induced (i.v. or i.c.v., 1.8 mg/kg) release of von Willebrand factor (vWF) was examined in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. SHR rats released significantly (P < 0.05) more vWF than WKY rats in response to LPS. LPS also inhibited factor VIII procoagulant activity (FVIII:c) which may indicate an increase in thrombin activity. Cultured cerebrovascular endothelial cells (EC) derived from both SHR and WKY rats, as well as human umbilical vein EC (HUVEC) cultures constitutively released vWF. Treatment with agonists including LPS, thrombin and tumor necrosis factor-alpha (TNF alpha) did not affect the in vitro secretion of vWF by cerebrovascular EC cultures but significantly upregulated vWF release by HUVEC cultures. Preincubation of cerebrovascular EC cultures with interleukin-1 (IL-1) +/- TNF alpha or co-culturing in the presence of LPS-activated syngeneic monocytes had no effect on vWF secretion. The findings demonstrate that conditions of hypertension may affect endothelial cells and make them more responsive to agonist stimulation and thereby increase secretion of vWF, an important factor in hemostasis as well as thrombosis. The capacity of LPS to significantly affect the in vivo secretion of vWF in SHR and WKY rats but not cultured cerebrovascular EC indicates that observed elevations in plasma vWF were not derived from cerebrovascular EC. It is suggested that hypertension may function as a risk factor for thrombotic stroke by influencing factors involved in coagulation processes, such as vWF and factor VIII:c.
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PMID:Agonist-stimulated release of von Willebrand factor and procoagulant factor VIII in rats with and without risk factors for stroke. 792 3

Heat stroke is a disease characterized by high fever. Cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-delta) play a major role in fever production. In the current studies, eight patients with heat stroke were enrolled in a cytokine studies. Serum cytokine levels of these patients were determined by EIA methods, and in vitro IL-1 and IL-1 inhibitor production were determined by murine thymocyte proliferation assay and/or EIA. Significantly high levels of circulating IL-1, TNF-delta, and IL-6 were demonstrated. Positive correlations were demonstrated between the body temperature and the level of IL-1 beta, and the cooling time and level of serum IL-1 beta. In addition, monocytes from heat stroke patients after complete recovery, secreted a much higher amount of IL-1 than did normal volunteers. However, there was no difference in IL-1 inhibitor production. These results indicate that cytokines may play a major role in the pathogenesis of heat stroke, and the ability to make different amounts of IL-1 in response to exogenous stimulation appear to be risk factors for an attack of heat stroke.
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PMID:The role of cytokines in heat stroke. 830 Jan 62

If one reviews the literature with zeal, it is increasingly apparent that few organs escape recruitment when IBD is chronic or progressive. Insights into mucosal pathophysiology have helped with understanding the more frequent extraintestinal manifestations, but the mechanisms attendant to the development of less common events (e.g. acute pancreatitis, concurrent gluten sensitive enteropathy, or active pulmonary disease) remain either poorly studied or obscure. It is particularly interesting, however, to read reports of abnormal pulmonary function, generally of the obstructive type, correlated to measurements of abnormal intestinal permeability in patients with either active pulmonary sarcoid or pulmonary involvement in Crohn's disease. It has been further speculated that similarities in the mucosal immune system of the lung and intestine are responsible for evidence of bronchial hyperreactivity in patients with active IBD. Finally, it is important to recognize that extensions of the inflammatory process are not restricted to the development of organ-based events but may be responsible for some of the most frequent systemic abnormalities detected in IBD patients. It is now also well confirmed that the cytokine environment in IBD can support activated coagulation and, in some clinical situations, overt vascular thrombosis. The cerebrovascular complications of IBD are well recognized and range from peripheral venous thrombosis to central stroke syndromes and pseudotumor cerebri. Reports of focal white matter lesions in the brains of patients with IBD or an increased incidence of polyneuropathy may be other clinical examples of regional microvascular clotting. Microvascular injury appears to be more ubiquitously present, with reports ranging from a speculated primary causative role (e.g., granulomatous vasculitis in the mesenteric circulation) to the utility of nailbed vasospasm, in Crohn's disease, as a clinical marker for disease activity. It is also reported that IL-6 suppression of erythropoietin production is a major feature of the chronic anemia seen in active IBD. Moreover, the capacity of peripheral monocytes from active IBD patients to secrete TNF and IL-8 is reported predictive for the degree of therapeutic response from recombinant erythropoietin. These collected observations constitute another excellent example of the symmetry between basic science and clinical utility. It is from the context of applied basic science that many future therapies will arise. Empiricism will lose much of its appeal as clinical observations will be increasingly translated into cellular language. Already in animal models, elemental diets diminish IL-6-related acute inflammatory injury, and reductions in dietary lipid alter the antigenicity of bacteria. Provocatively, in humans, unconfirmed reports have even associated diet therapy with the resolution of uveitis and pyoderma gangrenosum. It is likely that efforts will also be made to induce oral tolerance if specific triggering proteins are discovered or to alter bowel flora if such an arcane area of investigation becomes resurgent.
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PMID:Extraintestinal considerations in inflammatory bowel disease. 880 40

The original notion that the brain represented an "immune-privileged" organ lacking the capability to produce an inflammatory response to an injury, would appear no longer tenable. Indeed, accumulating evidence during the last decade has shown that the CNS can mount a well-defined inflammatory response to a variety of insults including trauma, ischemia, transplantation, viral infections, toxins as well as neurodegenerative processes. Many aspects of this centrally-derived inflammatory response parallel, to some extent, the nature of such a reaction in the periphery. Through the recent application of molecular biological techniques, new concepts are rapidly emerging as to the molecular mechanisms associated with the development of brain injury. In particular, the importance of cytokines, especially TNF alpha and IL-1 beta, as well as adhesion molecules, has been emphasized in the propagation and maintenance of a CNS inflammatory response. This review will summarize recent observations as to the involvement of these inflammatory mediators in CNS injury and lay claim to the possibility that inhibitors of peripheral inflammation may also be of benefit in treating CNS injuries such as stroke, head trauma, Alzheimer's disease and multiple sclerosis.
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PMID:The role of inflammation and cytokines in brain injury. 888 Jul 34

beta-Amyloid precursor protein (beta APP), transforming growth factor beta (TGF beta), and tumor necrosis factor-alpha (TNF alpha) are remarkably pleiotropic neural cytokines/neurotrophic factors that orchestrate intricate injury-related cellular and molecular interactions. The links between these three factors include: their responses to injury; their interactive effects on astrocytes, microglia and neurons; their ability to induce cytoprotective responses in neurons; and their association with cytopathological alterations in Alzheimer's disease. Astrocytes and microglia each produce and respond to TGF beta and TNF alpha in characteristic ways when the brain is injured. TGF beta, TNF alpha and secreted forms of beta APP (sAPP) can protect neurons against excitotoxic, metabolic and oxidative insults and may thereby serve neuroprotective roles. On the other hand, under certain conditions TNF alpha and the fibrillogenic amyloid beta-peptide (A beta) derivative of beta APP can promote damage of neuronal and glial cells, and may play roles in neurodegenerative disorders. Studies of genetically manipulated mice in which TGF beta, TNF alpha or beta APP ligand or receptor levels are altered suggest important roles for each factor in cellular responses to brain injury and indicate that mediators of neural injury responses also have the potential to enhance amyloidogenesis and/or to interfere with neuroregeneration if expressed at abnormal levels or modified by strategic point mutations. Recent studies have elucidated signal transduction pathways of TGF beta (serine/threonine kinase cascades), TNF alpha (p55 receptor linked to a sphingomyelin-ceramide-NF kappa B pathway), and secreted forms of beta APP (sAPP; receptor guanylate cyclase-cGMP-cGMP-dependent kinase-K+ channel activation). Knowledge of these signaling pathways is revealing novel molecular targets on which to focus neuroprotective therapeutic strategies in disorders ranging from stroke to Alzheimer's disease.
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PMID:Cellular signaling roles of TGF beta, TNF alpha and beta APP in brain injury responses and Alzheimer's disease. 906 86

Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis is common early after stroke. Hypercortisolism is a prominent manifestation. Normally the secretion of cortisol is regulated by adrenocorticotrophic hormone (ACTH), but recently an ACTH/cortisol dissociation after stroke was reported. Cytokines may influence the HPA axis, and plasma IL-6 levels are elevated following stroke. We investigated correlations between cortisol, ACTH, and cytokines, and between blood pressure and blood hormone levels early after stroke in seven stroke patients. All had neurological symptoms secondary to brain infarctions. Blood samples for analysis of cortisol, ACTH, IL-6, TNF alpha, norepinephrine, and epinephrine were collected four times daily, and 24-h blood pressure was measured. Plasma IL-6, but not ACTH, correlated significantly to serum cortisol. Catecholamine levels correlated with cytokine and cortisol levels. This study suggests that several routes for HPA-axis dysregulation is present early after stroke. Cytokine release may play an important role in this situation.
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PMID:Hypercortisolism after stroke--partly cytokine-mediated? 909 59


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