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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basic fibroblast growth factor (bFGF) is a potent neurotrophic and vasoactive peptide. Previous studies have shown that intraventricularly-administered bFGF reduces the size of cerebral infarcts following focal ischemia. In the current study, we tested the effects of intravenously-administered bFGF in a model of focal ischemia/reperfusion. The right middle cerebral artery of mature male Wistar rats was occluded by intraluminal suture. After 2 h of occlusion, the suture was removed and intravenous infusion of bFGF in vehicle (45 micrograms/kg/h) or vehicle alone was begun, lasting 3 h. Animals were weighed and evaluated neurologically until sacrifice 7 days after ischemia. The volume of cerebral infarcts was then determined by H and E staining and image analysis. We found a 40% reduction in infarct volume in bFGF- vs. vehicle-treated rats (n = 11 vs. 11, P < 0.05). Reduction in infarct volume was associated with improved neurological outcome and regained body weight in bFGF-treated animals (both P < 0.05). No change in blood pressure was found during bFGF treatment. These results show that the delayed intravenous administration of bFGF reduces infarct size in this model of focal ischemia/reperfusion. The mechanisms of infarct reduction may include direct cytoprotective and/or vasoactive effects.
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PMID:Delayed intravenous administration of basic fibroblast growth factor (bFGF) reduces infarct volume in a model of focal cerebral ischemia/reperfusion in the rat. 885 49

Basic fibroblast growth factor (bFGF), a prototypic member of a family of heparin-binding growth factors, is angiogenic both in vitro and in vivo. Increased levels and activity of bFGF have been documented in a variety of diseases, including tumors. We sought to determine whether bFGF might be similarly elevated in patients with clinical evidence of limb ischemia. Serum was obtained at the time of percutaneous revascularization from patients with symptomatic peripheral vascular disease (46 procedures were performed on 40 patients). An enzyme-linked immunoassay specific for bFGF was used (limit of detection, 1 pg/ml; range in normal subjects, 0 to 5 pg/ml). Among the 40 patients (28 men, 12 women, mean age 70 years) studied, elevated circulating bFGF (> or = 10 pg/ml) was detected in 36 samples (78%); levels ranged from 10 to 310 pg/ml (mean +/- SEM = 62 +/- 12). In 16 (89%) of 18 patients with both rest pain and nonhealing ischemic ulcers, serum bFGF levels were elevated up to 30 times normal values. In conclusion, circulating levels of bFGF are elevated in patients with vascular insufficiency and may reflect a physiologic response to limb ischemia.
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PMID:Elevated levels of basic fibroblast growth factor in patients with limb ischemia. 889 77

Basic fibroblast growth factor (bFGF) is a potent neurotrophic agent that promotes neuronal survival and outgrowth. Previous studies have shown that bFGF, administered intraventricularly or intravenously before or within hours after ischemia, reduces infarct size and neurological deficits in models of focal cerebral ischemia in rats. In the current study, we tested the hypothesis that bFGF, administered at later time points after ischemia, might improve behavioral recovery without affecting infarct size. Mature Sprague-Dawley rats received bFGF (1 microgram/injection) or vehicle by biweekly intracisternal injection for 4 weeks, starting at 1 day following permanent proximal middle cerebral artery (MCA) occlusion. Animals were examined every other day using four different behavioral tests to assess sensorimotor and reflex function. At 4 weeks after ischemia, there was no difference in infarct volume between bFGF- and vehicle-treated animals. There was, however, an enhancement in the rate and degree of behavioral recovery among bFGF-treated animals, as measured by all four tests. There were no apparent side effects of bFGF treatment, except that bFGF-treated animals tended to recover body weight more slowly than did vehicle-treated animals following stroke. The mechanisms of enhancement of behavioral recovery by bFGF require further study, but may include protection against retrograde neuronal death and/or stimulation of neuronal sprouting.
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PMID:Intracisternal basic fibroblast growth factor (bFGF) enhances behavioral recovery following focal cerebral infarction in the rat. 896 92

Basic fibroblast growth factor (bFGF) is a heparin-binding polypeptide with potent trophic and protective effects on brain neurons, glia and endothelia. In previous studies, we showed that intravenously administered bFGF reduced the volume of cerebral infarcts following permanent occlusion of the middle cerebral artery in rats. In the current study, we examined the time dependence of bFGF infusion on infarct reduction, and the effect of co-infusion of bFGF with heparin. We found a significant reduction in infarct volume when the bFGF infusion (50 microg/kg per h for 3 h) was begun up to 3 h, but not 4 h after the onset of ischemia. The infarct reducing effects of bFGF were not altered by co-infusion of heparin. These results are potentially important in light of the ongoing clinical trials of intravenous bFGF in acute stroke.
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PMID:Time window of infarct reduction by intravenous basic fibroblast growth factor in focal cerebral ischemia. 918 30

Basic fibroblast growth factor (bFGF) has been implicated in the changes in gene expression that, under pathological conditions such as ischemia or volume overload, lead to adult cardiomyocyte hypertrophy. In many tissues, one of the first events following cell activation by growth factors is an enhancement of the intracellular free calcium concentration, generated by fluxes from internal storage compartments and through channels of the plasma membrane. The present study was undertaken to determine whether cardiac myocytes isolated from adult rat ventricles express Ca2+-permeable channels activated by bFGF. Using the cell-attached mode of the patch-clamp technique, we observed that bFGF (from 0.1-10 nM) induced an increase of fast burst openings, mediated by Ca2+-permeable channels with low conductance (15 pS) and voltage-independence. Inside-out patch-clamp experiments revealed that inositol 1,4,5-trisphosphate (5 microM) enhanced the opening of Ca2+-permeable channels with similar properties as the bFGF-induced channels, indicating that IP3 may be a second messenger of this process. Confocal fluorescence imaging of intracellular free calcium provided direct evidence that bFGF induced an increase of cytoplasmic and nucleoplasmic free Ca2+ concentrations which were generated, in part, by Ca2+ influx through the plasma membrane. In conclusion, this study supports the presence, in the plasma membrane of adult cardiac myocytes, of messenger-activated calcium channels which could play key roles in the calcium-dependent pathways that are activated in response to growth factors.
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PMID:Basic FGF enhances calcium permeable channel openings in adult rat cardiac myocytes: implication in the bFGF-induced increase of free Ca2+ content. 934 63

Basic fibroblast growth factor (bFGF) is a biologically active polypeptide with mitogenic, angiogenic, and neurotrophic properties. In the present study, we examined the temporal and spatial expression profiles of bFGF mRNA and protein concentration in a focal cerebral ischemia model induced by transient occlusion of the right middle cerebral artery (MCA) and both common carotid arteries (CCAs). Results of Northern blot analysis shows a transient 2.5-fold increase in the 6.0 kb transcript of bFGF mRNA within the ischemic cortex of rats subjected to 60 min ischemic insult followed by 12 h of reperfusion. Although enhanced expression of bFGF mRNA was also noted in the ipsilateral hippocampus, the temporal induction profile appeared to be different from that of the ischemic cortex. A significant increase in bFGF mRNA was observed as early as 60 min following ischemia and remained elevated for up to 2 weeks after the onset of reperfusion. In situ hybridization studies revealed constitutive expression of bFGF mRNA in discrete brain regions of sham-operated animals. Following 60 min ischemia and 12 h reperfusion, increased expression of bFGF mRNA was observed in the ischemic cortex (both peri-infarct and infarct area). Increased expression of bFGF mRNA within the infarcted area is largely confined rostrally to the outer cortical layers of the infarct, an area with increased density of blood vessels. bFGF-like immunoreactivity was also detected in areas expressing bFGF mRNA. Furthermore, a striking increase in bFGF-like immunoreactivity was observed in the ipsilateral hippocampus. Double-staining with anti-GFAP antibody indicated that the majority of the bFGF-like immunoreactivity was localized in the astrocytes, however, not all astrocytes showed bFGF-like immunoreactivity. Some GFAP negative cell also showed bFGF-like immunoreactivity. In summary, increased expression of both bFGF mRNA and immunoreactivity following ischemia were located in the same brain regions. An increase in bFGF-like immunoreactivity after ischemic insult is likely due to an increase in the expression of its 6.0 kb bFGF mRNA transcripts. Although increased bFGF mRNA was observed in both ischemic cortex and ipsilateral hippocampus after ischemic insult, the temporal expression profiles differed. Results from the present study raise the possibility that increased expression of bFGF in the peri-infarcted area may limit the spread of ischemic injury.
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PMID:Induction of basic fibroblast growth factor (bFGF) expression following focal cerebral ischemia. 938 85

The effects of acidic fibroblast growth factor (FGF-1) and basic fibroblast growth factor (FGF-2) and a non mitogenic form of FGF1 on myocardial ischemia and reperfusion were assessed. Rats underwent 10 minutes of coronary artery occlusion followed by 24 hours of reperfusion. Creatinine kinase content of the affected myocardium showed that both fibroblast growth factors 1 and 2 effectively protected against ischemia reperfusion injury (p < 0.01), and that the vasoactive but nonmitogenic form of the FGF1 was equally protective (p < 0.01 versus control + vehicle). The results were confirmed by light and electron-microscopy histological studies. Histological evaluations after treatment with the non-mitogenic fibroblast growth factor 1 showed that it did not generate the severe hyperplasia and connective tissue disorganization observed with the native mitogenic proteins. The possibility of using a non-mitogenic form of fibroblast growth factor for cardio-protection circumvents many of the potentially undesirable effects that may derive from systemically introducing broad spectrum acting fibroblast growth factors in vivo. This myocardial protection observed 24 hours after the treatment with fibroblast growth factors, and the efficacy of the non-mitogenic form of the protein, also suggest that the protective effect of fibroblast growth factors may be due to the increased blood flow rather than to angiogenesis.
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PMID:Protection of rat myocardium by mitogenic and non-mitogenic fibroblast growth factor during post-ischemic reperfusion. 940 16

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have shown strong angiogenetic effects in ischemic animals; however, whether such a beneficial effect could be achieved using low doses remains to be determined. The effects of identical low-level doses of these substances on the creation of collateral circulation in canine acute hind limb insufficiency were evaluated. Anesthetized dogs that had undergone left femoral artery occlusion received 20 microg (2 microg/kg) intravenous boluses of either bFGF or VEGF 3 times at 2-day intervals for the first week only, animals on vehicle saline injection served as controls. All groups, control (n=8), bFGF-treated (n=8), and VEGF-treated (n=6) underwent angiography, blood flow measurement (in ml/min) on the day of ligation (day 0), and at 7, 14 and 28 days, then underwent ischemic limb muscle biopsy at 28 days. Angiogenic-treated groups showed remarkable enhanced collateral circulation at 7 days, which was maintained up to 28 days, and the main collateral source artery of the angiogenic-treated groups dilated by 14 days. Many neovascularized arterioles in specimens of the angiogenic groups were recognized without any tissue edema or necrosis. Even low doses of bFGF or VEGF were enough to augment collateral circulation with no side-effects, and short treatment after acute ischemia was effective. Low-dose bFGF or VEGF may be therapeutical effective options in patients with acute lower limb vascular disease.
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PMID:Low-dose basic fibroblast growth factor and vascular endothelial growth factor for angiogenesis in canine acute hindlimb insufficiency. 989 Feb 8

Basic fibroblast growth factor (bFGF) has been shown to induce angiogenesis in various animal models, but the methods of administration used experimentally are not clinically feasible. The objective of this study was to determine whether a single intracoronary bolus injection of bFGF would improve coronary perfusion in a porcine ischemic model that mimics clinical chronic ischemia. A copper coil studded with gold was delivered into the proximal right coronary artery of juvenile Yorkshire pigs and deployed by interventional techniques. After a four-week interval for stenosis maturation, bFGF (100 micrograms) was administered by bolus injection into the left coronary artery in five animals, and vehicle alone was administered in four animals. Angiogenesis and change in right coronary perfusion area were assessed two weeks later by angiography, myocardial contrast echocardiography and immunohistochemistry. The right coronary perfusion area increased significantly after treatment in all but one of the animals that received bFGF but not in any of the controls. Intimal hyperplasia was not induced by bFGF. Capillary density determined histochemically was not different in the two groups. In conclusion, in a porcine ischemic model, bFGF administered by a single bolus intracoronary injection into the contralateral artery improved antegrade perfusion into the ischemic territory although without histological evidence of angiogenesis. This preliminary work merits further investigation.
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PMID:Effect of a single bolus of intracoronary basic fibroblast growth factor on perfusion in an ischemic porcine model. 1037 18

The induction of growth factor synthesis in brain tissue by beta2-adrenoceptor agonists, such as clenbuterol, is a promising approach to protect brain tissue from ischemic damage. Clenbuterol (0.01-0.5 mg/kg) reduced the cortical infarct volume in Long-Evans rats as measured 7 days after permanent occlusion of the middle cerebral artery. Dosages of clenbuterol higher than 1 mg/kg showed no cerebroprotective effect due to a decrease in blood pressure and an increase in plasma glucose level. The increase in the mRNA level of nerve growth factor (NGF), basic fibroblast growth factor (basic FGF), and transforming growth factor-beta1 (TGF-beta1) mRNA in cortical and hippocampal tissue occurred earlier after middle cerebral artery occlusion and was more pronounced in animals treated with clenbuterol than in controls. In addition, glial fibrillary acidic protein (GFAP) mRNA expression was enhanced in astrocytes 6 h after ischemia in clenbuterol-treated animals. The results suggest that growth factor synthesis is enhanced in activated astrocytes and that this could be the mechanism of clenbuterol-induced cerebroprotection after ischemia.
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PMID:Clenbuterol induces growth factor mRNA, activates astrocytes, and protects rat brain tissue against ischemic damage. 1049 69


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