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

Interleukin-1 (IL-1) expression in the brain increases in response to acute and chronic insults, and IL-1 contributes directly to experimentally induced ischaemic, excitotoxic, and traumatic brain injury. Release and cleavage of active IL-1 beta may be achieved via purinergic P2X7 receptors and activation of caspase-1. The mechanisms of action of IL-1 are largely unknown, but may involve effects on glia, endothelia, and neurones, or on physical parameters within the brain such as temperature or acidity. The naturally occurring IL-1 receptor antagonist (IL-1ra) is currently being considered for treatment of stroke and other disorders.
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PMID:Interleukin-1 and neuronal injury: mechanisms, modification, and therapeutic potential. 1270 13

Ischemic stroke triggers lipid peroxidation and neuronal injury. Docosahexaenoic acid released from membrane phospholipids during brain ischemia is a major source of lipid peroxides. Leukocyte infiltration and pro-inflammatory gene expression also contribute to stroke damage. In this study using lipidomic analysis, we have identified stereospecific messengers from docosahexaenoate-oxygenation pathways in a mouse stroke model. Aspirin, widely used to prevent cerebrovascular disease, activates an additional pathway, which includes the 17R-resolvins. The newly discovered brain messenger 10,17S-docosatriene potently inhibited leukocyte infiltration, NFkappaB, and cyclooxygenase-2 induction in experimental stroke and elicited neuroprotection. In addition, in neural cells in culture, this lipid messenger also inhibited both interleukin 1-beta-induced NFkappaB activation and cyclooxygenase-2 expression. Thus, the specific novel bioactive docosanoids generated in vivo counteract leukocyte-mediated injury as well as pro-inflammatory gene induction. These results challenge the view that docosahexaenoate only participates in brain damage and demonstrate that this fatty acid is also the endogenous precursor to a neuroprotective signaling response to ischemia-reperfusion.
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PMID:Novel docosanoids inhibit brain ischemia-reperfusion-mediated leukocyte infiltration and pro-inflammatory gene expression. 1292

Inflammatory reaction following acute cerebral ischaemia exacerbates infarct size and neurological deficit. Brain resident cells localised within ischaemic region rapidly synthesise cytokines, proteins involved in cellular communication. The cytokines become important mediators of endothelial-leukocyte interactions leading to the influx of haematogenous inflammatory cells into the brain ischaemic region. Proinflammatory cytokines: tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) initiate inflammatory reaction and induce expression of other cytokines and inflammatory mediators. The presence of cytokines in brain infarct region has been shown in human and animal autopsy studies. Suppression of proinflammatory cytokines expression reduces brain infarct size in animal models of stroke. Increased levels of proinflammatory cytokines in cerebrospinal fluid and/or in serum of acute ischaemic stroke patients correlate with brain infarct volume and stroke severity and may have a predictive value for stroke outcome. This review presents cytokines studied in clinical and experimental strokes documenting that the molecules may exert not only detrimental but also neuroprotective effect on ischaemic brain.
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PMID:[Cytokines in clinical and experimental ischemic stroke]. 1504 69

Thrombolytic therapy not always improves clinical outcome in ischemic stroke patients. This could cause lymphomonocyte accumulation in the infarcted brain area. These produce an excessive amount of proinflammatory cytokines, such as IL-1 beta, IL-6 and TNF-alfa. The aim of our study was to determine ILs levels in fibrinolytic therapy treated patients, compared with healthy controls and to evaluate if the varying levels can predictors of neurological outcome. Eighteen patients underwent thrombolytic treatment with t-PA within 3 h. Plasma levels of IL-1 beta, IL-6, TNF-alfa and IL-10 were determined by ELISA method before and within 24 h after t-PA infusion and compared with controls. Significantly higher levels of IL-1 beta and Il-6 emerged in stroke patients before treatment compared with the control group (P < 0.05 and 0.04, respectively). Slightly higher plasma levels of TNF-alfa and lower plasma levels of IL-10 were also found at base line in stroke patients. After thrombolytic treatment no significant variations were observed in the levels of TNF-alfa and IL-6, whereas a trend toward lower values for IL-1 beta and higher levels for IL-10 was observed. Positive correlations among the values of IL-6, TNF-alfa and National Institute of Health Stroke Scale (NIHSS) at discharges were observed. A similar correlation with modified Rankin scale score at 3 month was found. Pre-treatment cytokine status seems to influence pre-and long-term clinical outcome. Therefore an investigation into the possible predictor of cytokines seem worthy.
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PMID:Different cytokine levels in thrombolysis patients as predictors for clinical outcome. 1517 33

Cerebral ischemia triggers acute inflammation, which exacerbates primary brain damage. Activation of the innate immune system is an important component of this inflammatory response. Inflammation occurs through the action of proinflammatory cytokines, such as TNF, IL-1 beta and IL-6, that alter blood flow and increase vascular permeability, thus leading to secondary ischemia and accumulation of immune cells in the brain. Production of these cytokines is initiated by signaling through Toll-like receptors (TLRs) that recognize host-derived molecules released from injured tissues and cells. Recently, great strides have been made in understanding the regulation of the innate immune system, particularly the signaling mechanisms of TLRs. Negative feedback inhibitors of TLRs and inflammatory cytokines have now been identified and characterized. It is also evident that lipid rafts exist in membranes and play a role in receptor-mediated inflammatory signaling events. In the present review, using this newly available large body of knowledge, we take a fresh look at studies of ischemic tolerance. Based on this analysis, we recognize a striking similarity between ischemic tolerance and endotoxin tolerance, an immune suppressive state characterized by hyporesponsiveness to lipopolysaccharide (LPS). In view of this analogy, and considering recent discoveries related to molecular mechanisms of endotoxin tolerance, we postulate that inhibition of TLR and proinflammatory cytokine signaling contributes critically to ischemic tolerance in the brain and other organs. Ischemic tolerance is a protective mechanism induced by a variety of preconditioning stimuli. Tolerance can be established with two temporal profiles: (i) a rapid form in which the trigger induces tolerance to ischemia within minutes and (ii) a delayed form in which development of protection takes several hours or days and requires de-novo protein synthesis. The rapid form of tolerance is achieved by direct interference with membrane fluidity, causing disruption of lipid rafts leading to inhibition of TLR/cytokine signaling pathways. In the delayed form of tolerance, the preconditioning stimulus first triggers the TLR/cytokine inflammatory pathways, leading not only to inflammation but also to simultaneous upregulation of feedback inhibitors of inflammation. These inhibitors, which include signaling inhibitors, decoy receptors, and anti-inflammatory cytokines, reduce the inflammatory response to a subsequent episode of ischemia. This novel interpretation of the molecular mechanism of ischemic tolerance highlights new avenues for future investigation into the prevention and treatment of stroke and related diseases.
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PMID:Inhibition of toll-like receptor and cytokine signaling--a unifying theme in ischemic tolerance. 1554 25

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

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

The older notion of a central nervous system existing in essential isolation from the immune system has changed dramatically in recent years as the body of evidence relating to the interactions between these two systems has grown. Here we address the role of a particular subset of immune modulatory molecules, the pro-inflammatory cytokines, in regulating neuronal function and viability in the dentate gyrus of the hippocampus. These inflammatory mediators are known to be elevated in many neuropathological conditions, such as Alzheimer's disease, Parkinson's disease and ischaemic injury that follows stroke. Pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), interleukin 1-beta (IL-1beta) and interleukin 18 (IL-18), have been shown to regulate neurotoxicity; although, due to the complexity of the cytokine action in neurons and glia, the effect may be either facilitatory or protective, depending on the circumstances. As well as their role in neurotoxicity and neuroprotection, the pro-inflammatory cytokines have also been shown to be potent regulators of synaptic function. In particular, TNF-alpha, IL-1beta and IL-18 have all been shown to inhibit long-term potentiation, a form of neuronal plasticity widely believed to underlie learning and memory, both in the early p38 mitogen activated protein kinase-dependant phase and the later protein synthesis-dependant phase. In this article we address the mechanisms underlying these cytokine effects in the dentate gyrus of the hippocampus.
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PMID:Pro-inflammatory cytokines and their effects in the dentate gyrus. 1776 28

The association between cytokines (IL-1 beta, sIL-4R, IL-6, IL-8, IL-10, IL-12, TNF-alpha) and subcortical white matter lesions, cortical atrophy and lacunar infarctions of the aging brain was investigated among 268 elderly community participants. Single pro- and anti-inflammatory cytokines were neither associated with WML nor with atrophy and lacunar infarction. An association between atrophy and the chemokine-cytokine factor (containing sIL-4R, IL-6, IL-8) remained significant after adjustment for age, gender, education, depressive symptoms, diabetes mellitus, cardiovascular diseases (stroke, TIA, myocardial infarction, myocardial insufficiency, arrhythmic heart), hypertension, body-mass index, smoking status and aggregation inhibitors as opposed to single cytokines. Atrophy of the parietal, temporal and occipital lobes was associated with the same cytokine-chemokine factor for both the whole sample or restricted to those without history of stroke/TIA. The results indicate that a combination of chemokine-cytokines rather than single cytokines may contribute to inflammatory processes associated with cortical atrophy in the aging brain.
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PMID:Association between cytokines and cerebral MRI changes in the aging brain. 1919 30

It was proven that compound C displays beneficial effects in models of inflammatory-induced anemia, ischemic stroke, and fibrodysplasia ossificans progressiva. Compound C influence on microglia, playing a major role in neuroinflammation, has not been evaluated yet. The aim of the present study was to determine the effect of compound C on cytokine release, NO, and reactive oxygen species (ROS) production. The rat microglial cultures were obtained by shaking the primary mixed glial cultures. Cytokine and nitrite concentrations were assayed using ELISA kits. ROS were assayed with nitroblue tetrazolium chloride. AMPK activity was assayed using the SAMS peptide. The expression of arginase I, NF-kappaB p65, and hypoxia-inducible factor-1 alpha (HIF-1 alpha) was evaluated using Western blot. Compound C displayed ambivalent effect depending on microglia basal activity. It up-regulated the release of TNF alpha and NO production and increased the expression of arginase I in non-stimulated microglia. However, compound C down-regulated IL-1 beta, IL-6 and TNF alpha release, NO, ROS production, and AMPK activity, diminished NF-kappaB and HIF-1 alpha expression, as well as increased arginase I expression in lipopolysaccharide (LPS)-stimulated microglia. Compound C did not affect iNOS expression and IL-10 and TGF-beta release in non-stimulated and LPS-stimulated microglia. The observed alterations in the release or production of inflammatory mediators may be explained by the changes in NF-kappaB, HIF-1 alpha, and arginase I expression and 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolinum bromide values in response to LPS, whereas the basis for the compound C effect on non-stimulated microglia remains to be investigated.
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PMID:Ambivalent effects of compound C (dorsomorphin) on inflammatory response in LPS-stimulated rat primary microglial cultures. 2816 17


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