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

Vascular endothelial growth factor (VEGF)-C plays an important role in lymphangiogenesis; however, functional responses of lymphatic vessels to VEGF-C have not been characterized. We tested the hypothesis that VEGF-C-induced activation of VEGF receptor (VEGFR)-3 increases lymphatic pump output. We examined the in vivo pump activity of rat mesenteric collecting lymphatics using intravital microscopy during basal conditions and during treatment with 1 nM recombinant VEGF-C, the selective VEGFR-3 agonist VEGF-Cys(156)Ser mutation (C156S; 1 nM), or 0.1 nM VEGF-A. Their specific responses were also analyzed during selective inhibition of VEGFR-3 with MAZ-51. Contraction frequency, end-diastolic diameter, end-systolic diameter, stroke volume index, pump flow index, and ejection fraction were evaluated. We also assessed arteriolar diameter and microvascular extravasation of FITC-albumin. The results show that both VEGF-C and VEGF-C156S significantly increased contraction frequency, end-diastolic diameter, stroke volume index, and pump flow index in a time-dependent manner. VEGF-A caused a different response characterized by a significantly increased stroke volume after 30 min of treatment. MAZ-51 (5 muM) caused tonic constriction and decreased contraction frequency. In addition, 0.5 and 5 muM MAZ-51 attenuated VEGF-C- and VEGF-C156S-induced lymphatic pump activation. VEGF-A caused vasodilation of arterioles, whereas VEGF-C and VEGF-C156S did not significantly alter arteriolar diameter. Also, VEGF-A and VEGF-C caused increased microvascular permeability, whereas VEGF-C156S did not. Our results demonstrate that VEGF-C increases lymphatic pumping through VEGFR-3. Furthermore, changes in microvascular hemodynamics are not required for VEGFR-3-mediated changes in lymphatic pump activity.
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PMID:Vascular endothelial growth factor-C stimulates the lymphatic pump by a VEGF receptor-3-dependent mechanism. 1740 Jul 13

Increased endogenous neurogenesis has a significant regenerative role in many experimental models of cerebrovascular diseases, but there have been very few studies in humans. We therefore examined whether there was evidence of altered endogenous neurogenesis in an 84-year-old patient who suffered a cerebrovascular accident 1 week prior to death. Using antibodies that specifically label neural stem/neural progenitor cells, we examined the presence of immunopositive cells around and distant from the infarcted area, and compared this with a control, age-matched individual. Interestingly, a large number of neural stem cells, vascular endothelial growth factor-immunopositive cells and new blood vessels were observed only around the region of infarction, and none in the corresponding brain areas of the healthy control. In addition, an increased number of neural stem cells was observed in the neurogenic region of the lateral ventricle wall. Our results suggest increased endogenous neurogenesis associated with neovascularization and migration of newly-formed cells towards a region of cerebrovascular damage in the adult human brain and highlight possible mechanisms underlying this process.
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PMID:Endogenous neurogenesis in the human brain following cerebral infarction. 1746 77

Cardiovascular disease refers to the class of diseases that involve the heart and/or blood vessels (arteries and veins). Most Western countries face high and ever-increasing rates of cardiovascular disease. Each year, more Americans are killed by heart disease than by cancer. Diseases of the heart alone cause 30% of all deaths, with other diseases of the cardiovascular system causing substantial further deaths and disability. Indeed, cardiovascular disease is the major cause of death and disability in the USA and most European countries. The development of the vascular systems requires an intricate interplay of molecules such as vascular endothelial growth factor and endothelial progenitor cells. A defective vascular repair/regeneration is thought to be responsible for propagation of atherosclerosis, a key feature of cardiovascular disease. This is partly attributed to a reduction in the circulating endothelial progenitor cells in peripheral blood. Patients with rheumatoid arthritis (RA) have a higher than average incidence of cardiovascular disease in comparison with the general population, with an increased risk of stroke and myocardial infarction, and an increased risk of fatality following myocardial infarction. This review focuses on the current evidence linking the role played by endothelial progenitor cells to the development of cardiovascular disease and why this might relate to the increased risk observed in RA patients.
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PMID:Circulating endothelial progenitor cells as a link between synovial vascularity and cardiovascular mortality in rheumatoid arthritis. 1747 12

Growth factors and their respective receptors are key regulators during development and for homeostasis of the nervous system. In addition, changes in growth factor function, availability or downstream signaling is involved in many neuropathological disorders like Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, stroke and brain tumours. Research of the recent years revealed that some growth factors, initially discovered as neural growth factors are also affecting blood vessels [e.g. nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF)]. Likewise, vascular growth factors, such as vascular endothelial growth factor (VEGF), which was previously described as an endothelial cell specific mitogen, also affect neural cells. The discovery of shared growth factors affecting the vascular and the nervous system is of relevance for potential therapies of vascular and neurological diseases. This review aims to give an overview about the growing field of common growth factors and receptors within the two different networks.
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PMID:Different networks, common growth factors: shared growth factors and receptors of the vascular and the nervous system. 1749 93

Recombinant human erythropoietin (rhEPO), a neurovascular protective agent, therapeutically supports angiogenesis after stroke by enhancing endogenous up-regulation of vascular endothelial growth factor (VEGF). Increased VEGF expression has been characterized to negatively impact the integrity of the blood brain barrier (BBB), causing brain edema and secondary injury. The present study investigated the rhEPO-induced BBB protection after stroke and how it might be achieved by affecting VEGF pathway. rhEPO treatment (5,000 U/kg, i.p., 30 min before stroke and once a day for three days after stroke) reduced Evans blue leakage and brain edema after ischemia. The expression of the BBB integrity markers, occludin, alpha-catenin and beta-catenin, in the brain was preserved in animals received rhEPO. rhEPO up-regulated VEGF expression; however, the expression of VEGF receptor-2 (fetal liver kinase receptor, Flk-1) was significantly reduced in rhEPO-treated animals three days after stroke. We propose that, disregarding increased VEGF levels, rhEPO protects against ischemia-induced BBB damage at least partly by down-regulating Flk-1 expression and the response to VEGF signaling in the acute phase after stroke.
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PMID:Erythropoietin prevents blood brain barrier damage induced by focal cerebral ischemia in mice. 1756 65

Cell injury leads to exposure of intracellular material and is associated with increased permeability of vessels in the vicinity of the damage. Here, we demonstrate that natural extracellular RNA as well as artificial RNA (poly-I:C), or single-stranded RNA but not DNA, significantly increased the permeability across brain microvascular endothelial cells in vitro and in vivo. RNA-induced hyperpermeability of tight monolayers of endothelial cells correlated with disintegration of tight junctions and was mediated through vascular endothelial growth factor (VEGF), reminiscent of heparin's activities. Antisense oligonucleotides against VEGF-receptor 2 (VEGF-R2) prevented the permeability-inducing activity of extracellular RNA and heparin completely. Hence, these polyanionic substances can lead to mobilization/stabilization of VEGF with the subsequent activation of VEGF-R2. In accordance with these functional data, strong binding of VEGF as well as other growth factors to RNA was demonstrable. In in vivo rat models of FeCl(3)-induced sinus sagittal is superior thrombosis and stroke/brain edema, pretreatment of animals with RNase (but not DNase) resulted in a significant reduction of vessel occlusion, infarct volume, and prevention of brain edema formation. Together, these results identify extracellular RNA as a novel natural permeability factor, upstream of VEGF, whereas counteracting RNase treatment may serve as new vessel-protective modality.
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PMID:Extracellular RNA mediates endothelial-cell permeability via vascular endothelial growth factor. 1757 19

Stroke rehabilitation is effective in some patients, however not so effective in others. Our ultimate aim is to use the clinical laboratory assessment as a tool for effectiveness discrimination in rehabilitation. Subjects were 15 stroke patients (68.1 +/- 12.7 years old) who were admitted to our convalescent rehabilitation wards. Fasting blood samples were analyzed for serum concentrations of hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and insulin-like growth factor-I (IGF-I) which are considered to be involved in hypermyotrophy using ELISA methods on admission and at discharge. Sixteen healthy control subjects (63.0 +/- 7.6 years old) were also employed. As accuracy control of these analyses, decrease of serum HGF after keeping at -20 degrees C for 499 days were measured. The concentration was 0.66ng/mL from 0.71 ng/mL and residual ratio was 94.0%. Reaction specificity to MW 60 kDa HGF antibody using the Western blot method was confirmed. Average HGF and VEGF were higher in stroke patients than those in control subjects. Average IGF-I was lower in stroke patients. The correlations between HGF, VEGF, and IGF-I and the score of activities of daily living expressed by the Functional Independence Measure (FIM) were calculated. Highest correlation coefficient of 0.67 (p < 0.01) was obtained between HGF at discharge and the FIM efficiency (the gain of the FIM during hospitalization divided by length of stay). The correlation coefficients related to VEGF or IGF showed lower value. High FIM efficiency denotes rapid recovery with vigorous exercise. HGF at discharge would reflect the result of high activity.
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PMID:[Relationship between cytokine concentration and activities of daily living in rehabilitation patients with stroke]. 1765 84

Buyang Huanwu Decoction is a classic formula for treating stroke-induced disability in traditional Chinese medicine (TCM). To explore its pharmacological basis, we investigated the effects of the whole formula and its herbal components on the neurological behavior performance and infarction volume in focal cerebral ischaemia rats. The neurological deficit scores and infarction volume were measured at days 3, 7 and 14 after 30 min of occlusion of middle cerebral artery. The results showed that Buyang Huanwu Decoction and its herbal components significantly improved the neurological behavior performances and reduced the infarction volume in the ischaemic brains. To elucidate the potential therapeutic mechanisms, we investigated the proliferation of progenitors by detecting the immunohistochemical staining of thymidine analog 5-bromo-2'-deoxyuridine (BrdU) and found that the formula stimulated the proliferation of the progenitors at hippocampus and subventricular zone (SVZ) in the ischaemic brains. As vascular endothelial growth factor (VEGF) and its receptor fetal liver kinase (Flk1) are important neurotrophic, neuroprotective and neuroproliferative factors, we studied the expressions of VEGF and Flk1 in the hippocampus, SVZ and cortex in the ischaemic brains and found that the formula led to increase the numbers of VEGF-positive and Flk1-positive cells in the SVZ and cortex in the ischaemic brains. The results indicate that the therapeutic effects of Buyang Huanwu Decoction for recovery of neurological deficits are associated with the stimulation of the proliferation of progenitors and the enhancement of the expressions of VEGF and Flk in ischaemic brains.
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PMID:Buyang Huanwu Decoction can improve recovery of neurological function, reduce infarction volume, stimulate neural proliferation and modulate VEGF and Flk1 expressions in transient focal cerebral ischaemic rat brains. 1769 86

Angiogenesis within human atherosclerotic plaques has an important role in plaque progression as immature blood vessels leak red blood cells and inflammatory mediators into the plaque center. Accumulation of free cholesterol from red blood cell membranes potentially increases the size of the necrotic core and triggers a chain of events that promote plaque destabilization. Antiangiogenic agents have been shown to prune some tumor vessels and 'normalize' the structure and function of the remaining vasculature, thereby improving the access of chemotherapeutic agents to tumors. We propose that antiangiogenic therapy can similarly stabilize vulnerable 'rupture-prone' plaques by pruning and normalizing immature intraplaque vessels, preventing further intraplaque hemorrhage. This normalization would limit necrotic core enlargement, further luminal narrowing and the degree of inflammation. Such normalization has been realized using vascular endothelial growth factor antagonists for the treatment of cancer and age-related macular degeneration. The development of this novel approach to prevent plaque progression might add to the armamentarium of preventive measures for acute myocardial infarction, stroke and sudden cardiac death.
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PMID:Antiangiogenic therapy for normalization of atherosclerotic plaque vasculature: a potential strategy for plaque stabilization. 1771 62

Spontaneous intracerebral hemorrhage (ICH) is one of the most devastating subtypes of stroke. Since angiogenesis is a fundamental process to brain development and repair by new blood vessel formation from pre-existing ones, mediated by numerous angiogenic factors including vascular endothelial growth factor (VEGF), the goal of the present work is to establish whether there is cerebral angiogenesis in rat brains with collagenase-induced ICH. Investigations were also performed to evaluate whether ICH alters expression of VEGF and its receptors Flt-1 and Flk-1. ICH was induced on adult male Sprague-Dawley rats by stereotactic injection of collagenase type VII into right globus pallidus. Angiogenesis was identified by hematoxylin-eosin stain and double immunolabeling method, and expression of VEGF and the receptors was evaluated by immunohistochemistry and quantitative real time reverse transcription-polymerase chain reaction. New vessels appeared around the hematoma and extended into it from 7 days, and 5-Bromo-2-Deoxyuridine-labeled nuclei in cerebral endothelial cells resided around the hematoma and the labeling peaked from 7 to 14 days. Expression of VEGF, Flt-1 and Flk-1 was observed in cerebral endothelial cells at the hemorrhagic basal ganglion, and increases of their mRNA persisted to 28 days. These findings suggest that ICH can induce cerebral angiogenesis and upregulation of VEGF, Flt-1 and Flk-1 and that modulation of angiogenesis via altering expression of VEGF and its receptors may be a potential strategy for promoting ICH repair.
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PMID:Cerebral angiogenesis after collagenase-induced intracerebral hemorrhage in rats. 1788 90


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