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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leukocytes play an important role in the development of ischemia-reperfusion injury. This study was conducted to ascertain whether synthetic peptides corresponding to the cell- and heparin-binding sequences of fibronectin that disturb leukocyte adhesion molecules were effective in neuronal protection after transient focal cerebral ischemia in rats. The authors evaluated the efficacy of peptides on infarction size, leukocyte infiltration in the ischemic tissue, and neurological outcome in rats subjected to 1 hour of cerebral ischemia and 48 hours of reperfusion. Twenty-one animals were divided into three groups: transient ischemia without treatment (Group I), transient ischemia with administration of vehicle (Group II), and transient ischemia with administration of fibronectin peptides (Group III). The mean myeloperoxidase activity (U/g wet wt) in the ischemic area was as follows: Group I, 0.19% +/- 0.05; Group II, 0.21% +/- 0.03; and Group III, 0.08% +/- 0.02. The mean size of the infarction as a percentage of the total hemispheric volume was as follows: Group I, 38.35% +/- 1.34%; Group II, 39.21% +/- 2.42%; and Group III, 25.81% +/- 4.87%. Group III showed a significant decrease in myeloperoxidase activity in the lesion and the infarction size was smaller when compared to Groups I and II (p < 0.05). The neurological grade in Group III was significantly better than in Groups I and II at 48 hours after reperfusion (p < 0.01). This study is the first to explore the therapeutic potential of synthetic fibronectin peptides in brain protection after transient focal ischemia, and the results also serve as a basis for studies of important cellular and molecular events that contribute to tissue damage.
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PMID:Synthetic fibronectin peptides and ischemic brain injury after transient middle cerebral artery occlusion in rats. 868 61

Leukocytes play an important role in the development of ischemia/reperfusion injury. Recent work in our laboratory has demonstrated that a mixture of synthetic fibronectin peptides to leukocyte adhesion molecules reduces ischemic brain damage after transient focal cerebral ischemia. The purpose of this study was to evaluate the efficacy of the individual peptides on leukocyte accumulation, infarct size, and neurological outcome in rats subjected to 1 h of cerebral ischemia and 48 h of reperfusion. Thirty-five animals were divided into five groups: transient ischemia without treatment (Group I), treatment with arginyl-glycyl-aspartic acid (RGD) peptide (Group II), connecting segment (CS)-1 peptide (Group III), fibronectin (FN)-C/H-V peptide (Group IV), and scrambled FN-C/H-V peptide (Group V). Groups III and IV showed a significant decrease in the degree of leukocyte infiltration in the lesion and in the infarct size (p < 0.05) when compared to Groups I, II, and V. The neurological grade of Groups III and IV was significantly better than in Groups I, II, and V at 48 h after reperfusion (p < 0.01). Thus, in addition to demonstrating the potential efficacy of synthetic peptides as therapeutic agents for ischemia-reperfusion, these results also offer new insights into the mechanisms of leukocyte arrest and recruitment in ischemia/reperfusion injury.
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PMID:Neuronal protection from cerebral ischemia by synthetic fibronectin peptides to leukocyte adhesion molecules. 889 83

Postischemic cerebral inflammation has been reported to contribute to ischemic brain damage. During inflammation, constituents of the extracellular matrix such as fibronectin and laminin are recognized by certain integrins or proteoglycans and play an important role in the cell adhesion process. The purpose of this study was to evaluate the efficacy of peptides derived from laminin on leukocyte accumulation, infarct size, and neurological outcome in rats subjected to 1 h of cerebral ischemia and 48 h of reperfusion. Forty-four animals were included in this study: transient ischemia without treatment (Group I), treatment with TG-1 peptide (Group II), GD-1 peptide (Group III), and GD-6 peptide (Group IV). Group II showed a significant reduction of the leukocyte accumulation (p < 0.001) and infarct size (p = 0.015) when compared with Group I. The neurological grade of Group II was also significantly better than in Group I at 48 h after reperfusion (p = 0.012). Based on these data, which are the first to explore the therapeutic potential of this peptide in cerebral ischemia, laminin peptide may offer a novel therapeutic approach to allaying injury in ischemic stroke.
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PMID:Laminin peptide ameliorates brain injury by inhibiting leukocyte accumulation in a rat model of transient focal cerebral ischemia. 923 17

Fibronectin performs essential roles in embryonic development and is prominently expressed during tissue repair. Two forms of fibronectin have been identified: plasma fibronectin (pFn), which is expressed by hepatocytes and secreted in soluble form into plasma; and cellular fibronectin (cFn), an insoluble form expressed locally by fibroblasts and other cell types and deposited and assembled into the extracellular matrix. To investigate the role of pFn in vivo, we generated pFn-deficient adult mice using Cre-loxP conditional gene-knockout technology. Here we show that pFn-deficient mice show increased neuronal apoptosis and larger infarction areas following transient focal cerebral ischemia. However, pFn is dispensable for skin-wound healing and hemostasis.
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PMID:Plasma fibronectin supports neuronal survival and reduces brain injury following transient focal cerebral ischemia but is not essential for skin-wound healing and hemostasis. 1123 23

In patients with thrombotic stroke, the occluded artery often reopens over time. This results through a natural dissolution of the occluding material, and fragments of the material may move downstream to obstruct distal arteries. The current study was undertaken to investigate the patency of brain microvessels at varying time intervals after injection of a preformed clot into the right internal carotid artery of rats. Cerebral microvessels in brain sections were visualized using immunohistochemistry for fibronectin (detecting existing microvessels) and Evans blue (visualizing perfused microvessels). The percentage of patent microvessels was calculated as the number of Evans blue-positive microvessels divided by the number of fibronectin-positive microvessels. In normal control animals, results showed that 98% +/- 3% (mean +/- SD) of microvessels in the cortex and 94% +/- 14% in the striatum were patent. In the ischemic animals, immediately after clot injection, microvessels in the cortex and striatum were occluded, mainly in the territory irrigated by the middle cerebral artery. One hour after clot injection, microvessels had reopened in most of the cortex but remained occluded in some portions of the striatum, possibly as a result of downstream movement of fragments formed from the original clot. By 3 hours after clot injection, microvessels in the cortex were patent in all animals, whereas in the striatum microvessels were patent in 50% of the animals. In the other 50%, small striatal perfusion deficits persisted. At 24 hours after clot injection, microvessels were patent in both the cortex and striatum of all animals except one. These findings suggest that intracerebral clots dissolve spontaneously in a relatively short period of time, but that fragments formed from the clot may obstruct more distal blood vessels. It is likely that clot fragments lodge in arteries with lower blood flow and poor collateral perfusion, where they continue to cause ischemia for a longer duration. These results may in part explain the resistance of the striatum to neuroprotective strategies used for the treatment of focal cerebral ischemia.
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PMID:Patency of cerebral microvessels after focal embolic stroke in the rat. 1132 27

TGF-beta1 has been demonstrated to be up-regulated in response to ischemic events both in animal models and in man. Demonstration of this up-regulation in the kidney following experimentally induced acute renal failure and in renal transplants complements similar findings in coronary and cerebral ischemia. Activation of TGF-beta1 occurs as a direct consequence of hypoxia, angiotensin II signaling and loss of extra cellular matrix (ECM) integrity, all of which occur in renal ischemia-reperfusion injury. TGF-beta1 thus up-regulates the synthesis of extracellular matrix components such as fibronectin and collagen IV providing a basis for the restoration of epithelial coverage in the regenerating tubule. TGF-beta1 also regulates epithelial tubular cell proliferation and differentiation. This response is quickly closed down in response to recovery of the kidney. This review examines the evidence linking TGF-beta1 activity to recovery from renal ischemia thereby constructing a hypothesis for the beneficial role of TGF-beta1 in the post ischemic kidney.
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PMID:Transforming growth factor-beta1 (TGF-beta1): a potential recovery signal in the post-ischemic kidney. 1221 20

Matrix metalloproteinases (MMPs) may contribute to the pathophysiology of cerebral ischemia by degrading matrix components in the neurovascular unit. In this study, the authors document a pathway by which MMPs interfere with cell-matrix interactions and trigger caspase-mediated cytotoxicity in brain endothelial cells. Hypoxia-reoxygenation induced endothelial cytotoxicity. Cytoprotection with zDEVD-fmk confirmed that cell death was partly caspase mediated. The temporal profile of caspase-3 activation was matched by elevations in MMP-2 and MMP-9. MMP inhibitors significantly decreased caspase-3 activation and reduced endothelial cell death. Degradation of matrix fibronectin confirmed the presence of extracellular proteolysis. Increasing integrin-linked kinase signaling with the beta1 integrin-activating antibody (8A2) ameliorated endothelial cytotoxicity. The results suggest that MMP-9 and MMP-2 contribute to caspase-mediated brain endothelial cell death after hypoxia-reoxygenation by disrupting cell-matrix interactions and homeostatic integrin signaling.
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PMID:Induction of caspase-mediated cell death by matrix metalloproteinases in cerebral endothelial cells after hypoxia-reoxygenation. 1524 Nov 80

Recent researches focused on the study of the role of the inflammation in the atherothrombotic pathogenesis of the acute cerebral ischemia. The aim of the study was to identify some acute phase proteins with possible role in the pathogenesis of the ischemic stroke. Some acute phase proteins were prospectively investigated by standard methods in sera of 78 patients with ischemic stroke in the first admission day. There were two groups according to neurological deficit one month after the ischemic stroke: good outcome and poor outcome. In the second group mean value of C-reactive protein (CRP) was 0.122 +/- 0.06 g/l (p < 0.01), mean value of C3 was 2.61 +/- 0.36 g/l (p < 0.01), mean value of C4 was 0.73 +/- 0.07 g/l (p < 0.05), mean value of alpha 1-antitrypsin (AAT) was 4.9 +/- 0.46 g/l (p < 0.01), mean value of alpha 1-antichymotrypsin (ACT) was 0.33 +/- 0.04 g/l (p < 0.01), mean value of alpha 1-acid glycoprotein (AGA) was 1.12 +/- 0.15 g/l, (p < 0.05), mean value of fibrinogen was 2.6 +/- 0.22 g/l (p < 0.01), mean value of haptoglobin was 2.8 +/- 0.33 g/l, (p < 0.05), mean value of transferrin was 2.8 +/- 0.26 g/l (p < 0.05), mean value of ferritin was 238 +/- 22.42 microg/l (p < 0.001), mean value of fibronectin was 2.14 +/- 0.17 g/l (p < 0.05), mean value of ceruloplasmin was 1.23 +/- 0.24 g/l (p < 0.01). High significant values of ferritine and significant values of CRP, C3, AAT, ACT and fibrinogen were observed in patients with poor outcome. The presented data suggest that the studied markers are useful to appreciate the role of the inflammatory reaction in the atherothrombotic pathogenesis of the ischemic stroke.
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PMID:Study of some markers of inflammation in atherothrombotic pathogenesis of acute ischemic stroke. 1552 46

Stroke is one of the leading causes of unnatural death and disability. No effective therapy is available. Recombinant human granulocyte colony-stimulating factor (rhG-CSF), as a mobilizing agent for bone marrow stem cells, can promote stem cell mobilization, homing to brain after cerebral ischemia. In the present study, the administration of G-CSF significantly increased number of CD34(+) cells in the marginal zone of the infarction. Rats receiving G-CSF had higher survival rate and lower infarction volume. Neurological behavior was improved, and the expression of fibronectin in the ischemic brain was increased, as compared to rats treated with vehicle. To mimic the ischemia-reperfusion injury in experimental animals, we employed hippocampal slice cultures that were first treated with oxygen and glucose deprivation (OGD) and then with oxygen-glucose resupply, finding that fibronectin significantly increased the neurite outgrowth of OGD hippocampal slices, upregulated the expression of Bcl-2 protein, and ameliorated the ultrastructure damage of OGD hippocampal slices.
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PMID:Fibronectin and neuroprotective effect of granulocyte colony-stimulating factor in focal cerebral ischemia. 1681 50

Local environmental conditions contribute to the activation state of cells. Extracellular matrix glycoproteins participate in cell-cell boundaries within the microvascular and extravascular tissues of the central nervous system and provide a scaffold for the local environment. These conditions are altered during focal cerebral ischemia (and other central nervous system disorders) when extracellular matrix boundaries are degraded or when matrix proteins in the vascular circulation enter the neuropil as the microvascular permeability barrier is degraded. Microglia in the resting state become activated after the onset of ischemia. During activation these cells can express a number of factors and proteases, including latent matrix metalloproteinase-9 (pro-MMP-9). Whereas MMP-9 and MMP-2 are generated early during focal ischemia in select models, their cellular sources in vivo are still under study. In vitro microglia cells activate and respond to exposure to specific matrix proteins (eg, vitronectin, fibronectin) that circulate. Certain MMP inhibitors, specifically tetracycline derivatives, can modulate microglial activation and reduce injury volume in limited studies. But, the injury reduction relies on preinjury exposure to the tetracycline. Other studies underway suggest the hypothesis that microglial cell activation and pro-MMP-9 generation during focal cerebral ischemia is promoted in part by matrix proteins in the circulation that extravasate into the neuropil when the blood-brain barrier is compromised. These matrix proteins are known to activate microglia through their specific cell surface matrix receptors.
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PMID:Microglial activation and matrix protease generation during focal cerebral ischemia. 1726 8


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