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

Previously, using a middle cerebral artery occlusion model in Wistar rat, we showed autonomic disturbances similar to those seen clinically and observed striking neurochemical changes in cortical and subcortical sites at 5 days following stroke. The neurochemical changes may account for functional recovery and/or autonomic disturbances after focal ischemia. To understand the possible mechanisms and to facilitate future studies, it is necessary to define the time-courses of these changes. Using immunohistochemical staining with the peroxidase-antiperoxidase reaction, the changes in several neuropeptides over the peri-ischemic region and the ipsilateral central and basolateral nucleus of the amygdala were investigated at different times after middle cerebral artery occlusion. In the experimental group, neuropeptide Y immunoreactivity appeared to increase by 6 hours in the peri-ischemic region. Using image analysis to quantify the staining intensity, the change became statistically significant at 1 day, peaked around 3 days, and subsided at 10 days. There was a delayed increase in neuropeptide Y in the ipsilateral basolateral nucleus of the amygdala with a peak around 3 days. Immunoreactive staining for leucine-enkephalin, dynorphin, and neurotensin demonstrated an increase that was localized to the ipsilateral central nucleus of the amygdala with a peak around 3 days and a return to baseline levels by 10 days. The results support a specific time-course for each of the neuropeptides studied and indicate that a survival time of 3 days after focal ischemia is the critical period for examining the relationship between neuropeptide responses and neuronal or functional recovery.
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PMID:Time-course of neuropeptide changes in peri-ischemic zone and amygdala following focal ischemia in rats. 749 57

In previous studies, we have used histological methods to characterize cellular changes, and validated the use of the myeloperoxidase (MPO) activity assay to quantitate increased neutrophil infiltration in ischemic stroke. We also identified increased leukotriene B4 (LTB4) binding sites as a potential marker for neutrophil infiltration into focal ischemic tissue. However, these studies were conducted at only one time-point, 24 h after ischemia. In the present study, we examined the full time-course of MPO activity and LTB4 receptor binding following middle cerebral artery occlusion (MCAO) made permanently (PMCAO) or transiently (160 min followed by reperfusion; TMCAO) in spontaneously hypertensive rats, and compared the results to previously characterized histologic changes in these models. Ischemic and contralateral (control) cortical tissue samples were assayed for MPO (U/g wet wt) and [3H]LTB4 receptor binding (fmol/mg protein). Following PMCAO, MPO activity significantly increased as early as 12 h and continued to increase over the next 5 d (p < 0.05). Following TMCAO, MPO activity was significantly elevated already after only 6 h of reperfusion and also continued to increase over the next 5 d of reperfusion (p < 0.05). LTB4 receptor binding and MPO activity were highly correlated during periods when both measures increased together (i.e., 0.5-5 d; p <0.01). However, by 15 d post-MCAO, LTB4 receptor binding remained elevated after MPO activity levels had returned to normal. This persistent LTB4 binding was associated with the significant gliosis that was characterized previously to persist in these models. The time-course of increased MPO activity and initially increased LTB4 binding post-MCAO correspond very well to our previous histological data that characterized the time-course for leukocyte infiltration under these conditions. Therefore, the increased MPO activity over time was associated with initial neutrophil and later mononuclear cell infiltration into ischemic tissue in these models. In addition, the present studies utilized histochemical analysis to demonstrate peroxidase activity in macrophages within the cerebral infarct following MCAO, thus validating that MPO activity originates from the later infiltrating mononuclear cells in addition to the early infiltrating neutrophils that had been previously characterized in the same manner. TMCAO produces a significantly larger and earlier increase in ischemic cortex MPO activity and a similar later increase in MPO activity compared to PMCAO treatment.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Time-related changes in myeloperoxidase activity and leukotriene B4 receptor binding reflect leukocyte influx in cerebral focal stroke. 775 44

Leukocyte depletion improves early postischemic ventricular performance in neonatal models of global myocardial ischemia. However, the rate of leukocyte reaccumulation after cardiopulmonary bypass and its subsequent impact on myocardial function is not known. This laboratory study examined the effect of leukocyte depletion on myocardial performance during the initial 6-hour period after bypass in an in situ, in vivo porcine model of neonatal cardiac surgery. Fifteen 3- to 5-day-old piglets (eight control and seven leukocyte depleted animals) were instrumented by placement of left ventricular short-axis sonomicrometry crystals and an intraventricular micromanometer catheter. Mechanical leukocyte depletion was achieved with Pall RC100 filters (Pall Biomedical, Inc., Fajardo, Puerto Rico) in the cardiopulmonary bypass circuit. Neonatal hearts were subjected to 90 minutes of hypothermic ischemia after a single dose of cold crystalloid cardioplegia. Two control animals died after the operation and were excluded from data analysis. Leukocyte filtration reduced the granulocyte count during initial myocardial reperfusion to 0.8% of control values. However, circulating granulocyte counts increased in leukocyte depleted animals throughout the postoperative period, reaching 68% of control values by 6 hours. Despite this rapid return of circulating granulocytes, animals subjected to leukocyte depletion had significantly better preservation of left ventricular performance (measured by preload recruitable stroke work, p < or = 0.02), left ventricular systolic function (measured by end-systolic pressure-volume relationship, p < or = 0.05), and ventricular compliance (p < or = 0.04) during the experiment. These changes in ventricular function were associated with a significant increase in left ventricular water content (p < or = 0.02) and tissue myeloperoxidase activity (p < or = 0.005) in control animals compared with leukocyte depleted animals. This study demonstrates that leukocyte depletion during initial reperfusion results in sustained improvement in postischemic left ventricular function despite the rapid return of granulocytes to the circulation.
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PMID:Temporary leukocyte depletion reduces ventricular dysfunction during prolonged postischemic reperfusion. 823 Dec 1

We tested the neuroprotective potential of neutrophil inhibitory factor (rNIF), a novel 41-kd recombinant glycoprotein derived from a hookworm, in a model of focal cerebral ischemia in the rat. Male Wistar rats were assigned to treatment with rNIF and vehicle. Middle cerebral artery occlusion (MCAO) for 2 hours was induced by insertion of an intraluminal suture. Infusion of the drug was initiated at the onset of reperfusion. Infarct volume was determined 48 hours after reperfusion. Neutrophils were measured within the ischemic tissue by myeloperoxidase (MPO) staining. Treatment with rNIF resulted in a 48% reduction in cerebral infarction compared with control animals (p < 0.01). Neutrophil accumulation in the ischemic brains of rNIF-treated rats was reduced significantly (p < 0.01) compared with control animals. The number of neutrophils within the infarcted tissue correlated positively with the size of the area of infarction (p < 0.001, r = 0.6) within representative cerebral coronal sections. We demonstrated a significant neuroprotective effect of rNIF with continuous treatment for 48 hours following 2 hours of MCAO. The neuroprotective effect was correlated with a reduced number of neutrophils within the ischemic tissue. These results demonstrate potential therapeutic properties of rNIF in the management of stroke.
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PMID:Neutrophil inhibitory factor is neuroprotective after focal ischemia in rats. 852 67

It is known that the peroxidation of LDL is a trigger for developing arteriosclerosis. The oxidized LDL is produced by either oxidative stress or a few oxidant. Selenium decreased in serum and some organs of stroke-prone spontaneously hypertensive rats (SHRSP), which is a cofactor of glutamine peroxidase. Serum magnesium decreased in patients with diabetes mellitus, with ischemic heart disease, with essential hypertension and with cerebral vascular lesions. Calcium to magnesium ratio was higher in some organs of SHRSP as compared to Wistar Kyoto rats (WKY). These changes accelerated vascular lesions in SHRSP.
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PMID:[Overview--suppression effect of essential trace elements on arteriosclerotic development and it's mechanism]. 858 7

A morphological and electrophysiological study was made on a unique primary mechanosensory neuron, the anterior gastric receptor (AGR), previously shown to arise from power-stroke muscle gm1 of the gastric mill system in the lobster foregut. Ultrastructural analysis of horseradish peroxidase injected AGR demonstrated that its peripheral dendrites do not ramify in muscle but are confined strictly to the connective tissue/epidermal interface in the tendon of gm1. These terminals are rich in mitochondria and at their very endings are free of glial cell wrapping, suggesting that they are the site at which mechano-transduction occurs. Extracellular axonal recordings from an in vitro neuromuscular preparation consisting of the gm1 muscle still attached to the stomatogastric nervous system, revealed that AGR is activated by passive stretch of gm1. The response to ramp stimuli displays dynamic and static components, both of which increase with the amplitude of applied stretch, while the dynamic component is also velocity sensitive. AGR is also activated by muscle contraction here elicited either by application of exogenous acetylcholine, the excitatory neurotransmitter for gm1, or by electrical stimulation of the motoneurons (GM) themselves. Consistent with a receptor lying in-series with its muscle, therefore, the effective stimulus of AGR in vivo is probably an increase in tension exerted on the tendon during active muscle contraction. In neuromuscular preparations including the bilateral commissural ganglia, stretching gm1 reflexly activates GM motoneurons at low stimulus strengths but leads to an inactivation of GM motoneurons at high stimulus strengths. This is consistent with earlier findings that both responses can be elicited by direct electrical stimulation of AGR. The functional implications of AGR's anatomical relationship with muscle gm1, the receptor's response properties, and its central effects on motor output to gm1 are discussed. Comparison is also drawn between this first reported example of a true tendon receptor in invertebrates and muscle receptors of vertebrates.
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PMID:Structural and functional characterization of a muscle tendon proprioceptor in lobster. 864 71

Cytokines and eicosanoids are well documented important mediators of endotoxemia. Bicyclic imidazoles are a novel class of nonsteroidal anti-inflammatory compounds that display unique pharmacological profiles by reducing cytokine production and arachidonic acid metabolism. In this study, we evaluated the ability of the bicyclic imidazole, SK&F 86002, to attenuate endotoxin-induced cardiopulmonary dysfunction. Pigs were randomly assigned to one of four groups: LPS (n = 5), given .5 microgram/kg/h 055:B5 Escherichia coli lipopolysaccharide (LPS) intravenously (i.v.) for 6 h; saline (n = 5); SK&F 86002 (n = 3), given 50 mg/kg SK&F 86002 orally 30 min prior to anesthesia; and SK&F 86002 + LPS (n = 5). Administration of LPS resulted in cardiopulmonary dysfunction characterized by decreased stroke volume and arterial oxygen tension, and increased room air alveolar-arterial oxygen gradient, pulmonary arterial pressure, pulmonary vascular resistance, and peak intratracheal pressure. Additionally, LPS administration was associated with leukopenia and increased pulmonary myeloperoxidase activity. Pretreatment with SK&F 86002 attenuated LPS induced hypotension, hypoxemia and bronchoconstriction and blocked the pulmonary hypertension. SK&F 86002 blocked the LPS-induced increase in myeloperoxidase activity, indicating a reduction in pulmonary neutrophil infiltration, but had no effect on systemic leukopenia. Pretreatment with SK&F 86002 significantly attenuated LPS-induced increases in plasma thromboxane B2 and tumor necrosis factor-alpha. We hypothesize that ameliorating effects of SK&F 86002 in this endotoxin model of cardiopulmonary dysfunction are related to inhibition of cytokine and eicosanoid biosynthesis.
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PMID:SK&F 86002, a dual cytokine and eicosanoid inhibitor, attenuates endotoxin-induced cardiopulmonary dysfunction in the pig. 894 52

Plasma activity of myeloperoxidase (MPO), malondialdehyde (MDA) and 4-hydroxynonenal (HNE) was measured prior to any treatment in 50 consecutive stroke patients with acute cerebral ischaemia, as well as in 14 healthy control subjects. Mann-Whitney-Wilcoxon test for unpaired data showed greater values of MPO (p < 0.01), MDA (p < 0.01) and HNE (p < 0.05) in stroke patients compared with controls. Considering as covariates the level of consciousness (GCS < 9 vs > or = 9), possible sources of emboli (yes vs no), leukocyte count (< 10 x 10(9)/1 vs > or = 10 x 10(9)/1) and relevant comorbid diseases (yes vs no), exact multiple logistic regression analysis indicated that only the presence of possible cardiac sources of emboli was associated with changes in by-products of lipid peroxidation. If confirmed in a larger series of subjects, our results could have therapeutic implications, providing more support for the use of free radical scavengers in the acute care of stroke patients with a possible cardioembolic aetiology.
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PMID:Plasma lipoperoxidative markers in ischaemic stroke suggest brain embolism. 984 45

Earlier we indicated that neutrophilic invasion into cerebral parenchyma is an important step in rat cerebral ischemia-reperfusion injury and the production of chemotactic factors, cytokine-induced neutrophil chemoattractant (CINC) precede the neutrophilic invasion. The aim of the present study was to evaluate the role of CINC production and the therapeutic possibility of blocking CINC activity in the transient ischemic brain damage in rats. Focal transient ischemia was produced by intraluminal occlusion of the right middle cerebral artery for 60 min. An enzyme immunoassay was used to measure the brain concentration of CINC and myeloperoxidase activity in ischemic areas was measured as a marker of neutrophilic accumulation. An immunohistochemical staining technique was used to detect the immunopositive cells for anti-CINC antibody. Further, application of anti-CINC antibody or anti-neutrophil antibody to rats was used to evaluate the role of CINC production. In ischemic areas, CINC production was detected and peaked 12 h after reperfusion, which followed 60 min of ischemia. Intraperitoneal injection of anti-neutrophil antibody 24 h before and immediately after reperfusion significantly reduced the brain water content and partially reduced the CINC production in ischemic areas. Further, immunohistochemical staining showed that anti-CINC antibody was found on the endothelial surface of venules and on parts of neutrophils that had invaded the ischemic area 6 to 24 h after reperfusion. Also, treatment with anti-CINC antibody reduced ischemic edema formation 24 h after reperfusion and the size of infarction areas 7 days after reperfusion. It thus appears that CINC, mainly produced by endothelium activated by factors released from neutrophils, plays an important role in ischemic brain damage. Furthermore, the blocking of CINC activity with antibody suggests an immuno-therapeutic approach to the treatment of stroke patients.
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PMID:New therapeutic possibility of blocking cytokine-induced neutrophil chemoattractant on transient ischemic brain damage in rats. 921 68

CD105 (endoglin) is a receptor for transforming growth factor beta (TGFbeta). Although methods to measure soluble forms of TGFbeta and CD105 have been published, no assay is available to quantify the receptor-ligand complexes. We describe both an indirect enzyme-linked immunosorbent assay for the quantitation of soluble CD105-TGFbeta1 and the characterization of the complexes by immunoprecipitation and immunoblotting. Mab E9, specifically reactive with CD105, was utilised as the capture reagent in the ELISA system. Detection of complexes was achieved using chicken antibody against TGFbeta1 and the subsequent detection of bound antibody demonstrated by the addition of anti-species antiserum conjugated to horseradish peroxidase (HRP). By using enhanced chemiluminescence and optimised antibodies, the assay was made sufficiently sensitive and reproducible to detect low levels of circulating complexes. Whether the assay had any practical applications was evaluated in breast cancer patients. Plasma levels of CD105-TGFbeta1 were significantly elevated in 59 patients with breast cancer compared to 52 age matched normal women (p < 0.001). Immunoprecipitation using a rabbit anti-CD105 antibody, which reacts with both dimeric and monomeric CD105, and immunoblotting showed that three molecular forms of CD105-TGFbeta1 complexes > 200, 195, and 125 kDa existed in the plasma. We believe these represent the oligomer, dimer and probably the protease degraded form of CD105 complexed to TGFbeta1. The resistance to hypertonic solution, SDS and heat treatment suggested that the soluble CD105-TGFbeta1 complex may be linked by covalent bonds. The measurement of CD105-TGFbeta complexes in the circulation may have important clinical applications not only in cancer but also in patients with other angiogenic diseases such as rheumatoid arthritis, myocardial infarction and stroke.
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PMID:Immunodetection and characterisation of soluble CD105-TGFbeta complexes. 981 25


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