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

Inflammation and oxidative stress are involved in brain damage following stroke, and tryptophan oxidation along the kynurenine pathway contributes to the modulation of oxidative stress partly via the glutamate receptor agonist quinolinic acid and antagonist kynurenic acid, and via redox-active compounds such as 3-hydroxyanthranilic acid. We have confirmed that following a stroke, patients show early elevations of plasma neopterin, S100B and peroxidation markers, the latter two correlating with infarct volume assessed from computed tomography (CT) scans, and being consistent with a rapid inflammatory response. We now report that the kynurenine pathway of tryptophan metabolism was also activated, with an increased kynurenine : tryptophan ratio, but with a highly significant decrease in the ratio of 3-hydroxyanthranilic acid : anthranilic acid, which was strongly correlated with infarct volume. Levels of kynurenic acid were significantly raised in patients who died within 21 days compared with those who survived. The results suggest that increased tryptophan catabolism is initiated before or immediately after a stroke, and is related to the inflammatory response and oxidative stress, with a major change in 3-hydroxyanthranilic acid levels. Together with previous evidence that inhibiting the kynurenine pathway reduces brain damage in animal models of stroke and cerebral inflammation, and that increased kynurenine metabolism directly promotes oxidative stress, it is proposed that oxidative tryptophan metabolism may contribute to the oxidative stress and brain damage following stroke. Some form of anti-inflammatory intervention between the rise of S100B and the activation of microglia, including inhibition of the kynurenine pathway, may be valuable in modifying patient morbidity and mortality.
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PMID:Altered kynurenine metabolism correlates with infarct volume in stroke. 1789 81

Conventional ways of monitoring reperfusion in acute ischemic stroke have several limitations. In searching for an alternative, we evaluated biochemical serum markers of stroke change in relation to reperfusion. N-acetylaspartate (NAA) is a small amino acid synthesized by neuronal mitochondria, which can be released in the extracellular space after reperfusion in animal models of brain ischemia. S100B is a well-known peripheral marker of brain damage in various neurologic diseases, including stroke. Serum samples were analyzed from 13 patients with ischemic stroke who were either treated conservatively or with recombinant tissue plasminogen activator. Blood was drawn at baseline; after 30 minutes; after 1, 2, 4, and 8 hours; and between 12 to 24 hours. Serum concentrations of NAA were analyzed using a gas chromatography-mass spectrometry method. S100B was analyzed using an automated immunoluminometric assay. Reperfusion was assessed using transcranial Doppler and clinical criteria. Reperfusion (n = 4) was associated with a transient rapid increase in serum NAA levels. Such an early rapid increase of NAA was not observed for patients with persistent occlusion at 12 to 24 hours (n = 4) and patients with no occlusion on baseline transcranial Doppler (n = 5). NAA peak levels and area under the curve values were significantly higher after reperfusion in comparison with normal transcranial Doppler findings or persistent occlusion (P = .003 and P = .05, respectively). No differences were found between these groups for S100B levels. In patients with acute ischemic stroke, serum NAA levels transiently raise after reperfusion.
J Stroke Cerebrovasc Dis
PMID:N-acetylaspartate: serum marker of reperfusion in ischemic stroke. 1790 83

Activation of the receptor for advanced glycation endproducts (RAGE) by its multiple ligands can trigger diverse signaling pathways with injurious or pro-survival consequences. In this study, we show that Rage mRNA and protein levels were stimulated in the mouse brain after experimental stroke and systemic hypoxia. In both cases, RAGE expression was primarily associated with neurons. Activation of RAGE-dependent pathway(s) post-ischemia appears to have a neuroprotective role because mice genetically deficient for RAGE exhibited increased infarct size 24 h after injury. Up-regulation of RAGE expression was also observed in primary neurons subjected to hypoxia or oxygen-glucose deprivation, an in vitro model of ischemia. Treatment of neurons with low concentrations of S100B decreased neuronal death after oxygen-glucose deprivation, and this effect was abolished by a neutralizing antibody against RAGE. Conversely, high concentrations of exogenous S100B had a cytotoxic effect that seems to be RAGE-independent. As an important novel finding, we demonstrate that hypoxic stimulation of RAGE expression is mediated by the transcription factor hypoxia-inducible factor-1. This conclusion is supported by the finding that HIF-1alpha down-regulation by Cre-mediated excision drastically decreased RAGE induction by hypoxia or desferrioxamine. In addition, we showed that the mouse RAGE promoter region contains at least one functional HIF-1 binding site, located upstream of the proposed transcription start site. A luciferase reporter construct containing this RAGE promoter fragment was activated by hypoxia, and mutation at the potential HIF-1 binding site decreased hypoxia-dependent promoter activation. Specific binding of HIF-1 to this putative HRE in hypoxic cells was detected by chromatin immunoprecipitation assay.
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PMID:Hypoxia-inducible factor-1 mediates neuronal expression of the receptor for advanced glycation end products following hypoxia/ischemia. 1794 94

The aim of this study is to determine S100B protein levels in serum and cerebrospinal fluid (CSF) in patients with different forms of neruopsychiatric systemic lupus erythematosus (NPSLE). There were 157 SLE patients (65 with and 92 without NPSLE, and 20 patients without rheumatic diseases served as controls) recruited in the present study. Serum and CSF S100B protein levels were measured by ELISA assay. Serum S100B protein levels in patients with NPSLE (0.179 +/- 0.095 microg/l) were significantly higher than the levels in patients without NPSLE (0.110 +/- 0.091 microg/l; p < 0.001) and in controls (0.103 +/- 0.065 microg/l; p = 0.005). Thus, the differences in serum levels between non-NPSLE patients and controls had no statistical significance. The serum and CSF S100B protein contents in patients with organic brain syndrome, seizures, cerebral vascular accident, and psychosis were significantly higher than those in controls (all p < 0.001). However, there was no significant difference in serum and CSF S100B protein levels among patients with headache, patients with neuropathy, and controls. In conclusion, serum and CSF S100B levels were raised in NPSLE, especially concerning patients with organic brain syndrome, seizures, cerebral vascular accident, and psychosis. The results obtained imply that S100B protein is possibly an available and complementary biochemical marker within evaluation of NPSLE and deserves further study.
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PMID:Expression of S100B protein levels in serum and cerebrospinal fluid with different forms of neuropsychiatric systemic lupus erythematosus. 1795 79

There is a current interest in dietary compounds, such as green tea polyphenols, that can favor protection against a variety of brain disorders, including Alzheimer's disease, ischemia, and stroke. The objective of the present study was to investigate the effects of (-)-epicatechin-3-gallate (ECG), one of three three major green tea antioxidants, on C6 lineage cells. Here, we evaluated cell morphology and integrity and specific astrocyte activities; glutamate uptake and secretion of S100B in the presence of 0.1, 1 and 10 microM ECG. During 6 h of incubation, cell morphology was altered only at 10 microM ECG; however, after 24 h of treatment, cells become stellate in the presence of all concentrations of ECG. Loss of cell integrity was observed after 24 h with 10 microM ECG and represented only 6% of cells, in contrast with 2% observed at basal conditions. ECG (1-10 microM) induced a decrease (about 36%) in glutamate uptake after 1 h of incubation. After 6 h, an opposite effect occurred and ECG induced a sustained increase in glutamate uptake of about 70% from 0.1 microM. In addition, a significant increase in S100B was observed at 1 microM ECG (36%) and 10 microM ECG (69%) after 1 h, in contrast to 6 h of treatment, where all doses of ECG induced a significant increase (about 60%) in S100B secretion. These data demonstrate that ECG induces a significant improvement in glutamate uptake and S100B secretion in C6 cells, indicating that ECG could contribute to the neuroprotective role of astroglial cells.
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PMID:Epicatechin gallate increases glutamate uptake and S100B secretion in C6 cell lineage. 1806 51

S100B is a 21-kDa, Ca(2+)-binding protein that is expressed in the central nervous system. Although the peripheral S100B level is significantly correlated with stroke outcome, the mechanisms responsible for increase in the peripheral S100B level have not been precisely investigated in animal ischemic stroke models. To justify the use of peripheral S100B as a common biomarker between stroke patients and animal models, the mechanisms responsible for increases in the peripheral S100B level after focal cerebral ischemia should be clarified. In the present study, we investigated correlations between the cerebrospinal and serum S100B levels to determine whether increase in peripheral S100B properly reflect the conditions inside the central nervous system. From each rat, cerebrospinal fluid and serum samples were collected at 24, 48, 72, or 120 h after the onset of photochemically induced thromboembolic stroke in rats. Our results indicated a difference in the kinetics of cerebrospinal and serum S100B. Among the four sampling points, the serum S100B levels were most strongly correlated with the cerebrospinal S100B levels at 48 h after PIT stroke onset. While the serum S100B level may be a useful biomarker of stroke in experimental or clinical studies, the timing of S100B measurements should be carefully selected to ensure that the serum S100B level properly reflects the conditions in the central nervous system.
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PMID:Relationship between cerebrospinal and peripheral S100B levels after focal cerebral ischemia in rats. 1835 61

Body fluid biomarkers of central nervous system damage may help improve the prognostic and diagnostic accuracy in ischemic stroke. We studied 53 patients. Stroke severity and outcome was rated using the National Institutes of Health Stroke Scale and modified Rankin scale. Ferritin, S100B, and NfH were measured in cerebrospinal fluid (CSF) and serum. Infarct volume was calculated from T2W images. CSF S100B (median 1.00 ng/mL) and CSF ferritin (10.0 ng/mL) levels were elevated in patients with stroke compared with control subjects (0.62 ng/mL, P < .0001; 2.34 ng/mL, P < .0001). Serum S100B (0.09 ng/mL) was higher in patients with stroke compared with control subjects (0.01 ng/mL). CSF S100B levels were higher in patients with a cardioembolic stroke (2.88 ng/mL) than in those with small-vessel disease (0.89 ng/mL, P < .05). CSF S100B levels correlated with the National Institutes of Health Stroke Scale score on admission (R = 0.56, P < .01) and the stroke volume (R = 0.44, P = .01). CSF S100B and NfH-SMI35 levels correlated with outcome on the modified Rankin scale. CSF S100B levels were related to stroke severity and infarct volume and highest in cardioembolic stroke.
J Stroke Cerebrovasc Dis
PMID:Glial and axonal body fluid biomarkers are related to infarct volume, severity, and outcome. 1858 39

S100B is a 21-kD, Ca2+-binding protein that is mainly expressed in astroglial cells and Schwann cells in the nervous system. The S100B level in peripheral blood samples is reportedly elevated in patients with various central nervous system disorders including ischemic stroke. Since an elevated peripheral S100B level seems to be related closely to cerebral vascular damage involving a blood-brain barrier (BBB) disruption, we hypothesized that the peripheral S100B levels may increase earlier and to a greater extent after stroke onset when the cerebral blood vessels are severely damaged and spontaneous cerebral hemorrhage exists. In the present study, the relationship between an increase in the serum S100B level and cerebral hemorrhage was investigated within 24 h of stroke onset. A rat model for focal cerebral ischemia using an intraluminal filament method was utilized because cerebral hemorrhage is sometimes observed as a result of vascular damage caused by the filament. Significant increases in the serum S100B levels of rats with cerebral hemorrhage were observed from 1 h after stroke onset, compared with the levels in rats without cerebral hemorrhage. The early increases in serum S100B were not correlated with the brain infarct volumes at 3 h after stroke. These findings suggest that the serum S100B level increases earlier, reflecting the existence of cerebral hemorrhage.
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PMID:Early increases in serum S100B are associated with cerebral hemorrhage in a rat model of focal cerebral ischemia. 1862 Oct 38

There is a current interest in dietary compounds (such as trans-resveratrol) that can inhibit or reverse oxidative stress, the common pathway for a variety of brain disorders, including Alzheimer's disease and stroke. The objective of the present study was to investigate the effects of resveratrol, under conditions of oxidative stress induced by H(2)O(2), on acute hippocampal slices from Wistar rats. Here, we evaluated cell viability, extracellular lactate, glutathione content, ERK(MAPK) activity, glutamate uptake and S100B secretion. Resveratrol did not change the decrease in lactate levels and in cell viability (by MTT assay) induced by 1mM H(2)O(2), but prevented the increase in cell permeability to Trypan blue induced by H(2)O(2). Moreover, resveratrol per se increased total glutathione levels and prevented the decrease in glutathione induced by 1mM H(2)O(2). The reduction of S100B secretion induced by H(2)O(2) was not changed by resveratrol. Glutamate uptake was decreased in the presence of 1mM H(2)O(2) and this effect was not prevented by resveratrol. There was also a significant activation of ERK1/2 by 1mM H(2)O(2) and resveratrol was able to completely prevent this activation, leading to activity values lower than control levels. The impairments in astrocyte activities, induced by H(2)O(2), confirmed the importance of these cells as targets for therapeutic strategy in brain disorders involving oxidative stress. This study reinforces the protective role of resveratrol and indicates some possible molecular sites of activity of this compound on glial cells, in the acute damage of brain tissue during oxidative stress.
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PMID:Resveratrol protects against oxidative injury induced by H2O2 in acute hippocampal slice preparations from Wistar rats. 1883 40

S100B, a 21-kD Ca(2+) binding protein expressed in Schwann cells and astroglia, has often been reported as a promising biomarker for ischemic stroke. In addition to ischemic stroke, the peripheral S100B level may also be useful as a biomarker for intracerebral hemorrhage (ICH). However, the kinetics and characterization of peripheral S100B in patients or experimental animal models with ICH have not been carefully examined. The present study investigated the kinetics and characteristics of the serum S100B level in a rat collagenase-induced ICH model. The serum S100B kinetics and the time-course of brain edema and hematoma formation were examined. Then, the correlations between the elevated serum S100B level and brain edema or hematoma formation were investigated. A transient elevation of serum S100B that peaked at 6 h after ICH induction was observed. The single measurement of serum S100B at 6 h after ICH induction was significantly correlated with brain edema formation and the maximal extent of the hematoma volumes. These results suggest the significance of serum S100B as a biomarker of brain damage resulting from ICH.
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PMID:Serum S100B, brain edema, and hematoma formation in a rat model of collagenase-induced hemorrhagic stroke. 1902 32


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