Gene/Protein Disease Symptom Drug Enzyme Compound
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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) has shown a neurotrophic effect in the neurons of several CNS areas. In vivo, it contributes to restore neurochemical and morphological deficits in different rodent models of brain damage, including rats with brain damage induced by hypoxia/ischemia when FGF was intramuscularly (i.m.) administered. Toxicological and immunological studies performed in rats, mice and volunteers showed no evidence of side-effects. Bovine FGF was i.m. administered in children with mental retardation caused by perinatal hypoxia, aged 1-15 years, at dosages of 0.4 or 0.28 microgram kg-1, once or twice a month, over 7-12 months. Group A [n = 12; 6 treated (T), 6 controls (Ct)], group B (n = 16; 8 T, 8 Ct) and group C (n = 67; 45 T, 22 Ct) were evaluated with the P. A. R. scale, the WISC-RM and the Gesell scale, respectively. Development increased significantly in treated children from groups A (P < 0.02) and C (P < 0.001), and IQ rose by more than 10 points (P < 0.001) in group B patients.
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PMID:Psychometric analysis in children with mental retardation due to perinatal hypoxia treated with fibroblast growth factor (FGF) and showing improvement in mental development. 812 97

Basic fibroblast growth factor is a polypeptide with potent multipotential trophic effects on central nervous system cells, including neurons, glia, and endothelial cells. In particular, it promotes the survival of a wide variety of brain neurons in vitro, and protects these neurons against the effects of several neurotoxins, including excitatory amino acids, hypoglycemia, and calcium ionophore. Since lack of substrate delivery, excitatory amino acid toxicity, and calcium entry into cells appear to be important processes in neuronal death after ischemia, we tested the hypothesis that pretreatment with basic fibroblast growth factor limits infarct size in a model of focal cerebral ischemia in vivo. Mature male Long-Evans rats received either continuous intraventricular infusion of basic fibroblast growth factor (1.2 micrograms/day; with or without heparin, added to stabilize the growth factor) or vehicle alone for 3 days before focal ischemic infarcts were made in the right lateral cerebral cortex by permanent distal middle cerebral artery occlusion and temporary (45-minute) bilateral carotid occlusion. Intraoperative measurements of core temperature, arterial blood pressure and blood gases, blood glucose concentration, and hematocrit, and postoperative measurements of temperature revealed no differences among vehicle- versus basic fibroblast growth factor-treated animals. Twenty-four hours later, animals were killed, brains were removed and stained to visualize cortical infarcts, and infarct volume was determined by image analysis. Overall, we found a 25% reduction in infarct volume in basic fibroblast growth factor- (N = 25) versus vehicle-treated (N = 23) animals (p < 0.01). This reduction was not enhanced by the addition of heparin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pretreatment with intraventricular basic fibroblast growth factor decreases infarct size following focal cerebral ischemia in rats. 815 72

An aberrant elevation in intraneuronal calcium levels resulting from energy failure and excitatory amino acid receptor activation is believed to play a major role in the neuronal damage and death that occur in stroke. We have found that several growth factors can protect cultured rat hippocampal and septal neurons and human cortical neurons from excitotoxic damage caused by glucose deprivation or hypoxia. Using the calcium indicator dye fura 2 and whole-cell patch-clamp recording, we found that glucose deprivation initially results in calcium current inhibition and a reduction in intraneuronal free calcium levels without morphological signs of cell damage. After 12 to 16 hours of glucose deprivation, a large elevation in intraneuronal calcium levels occurred that involved N-methyl-D-aspartate receptor activation and mediated the cell damage and death. Basic fibroblast growth factor (bFGF), nerve growth factor (NGF), and insulin-like growth factors (IGF-I and IGF-II) each prevented, in a dose-dependent manner, glucose deprivation-induced loss of calcium homeostasis and neuronal damage. The growth factors were effective to varying degrees when added up to 12 hours after the onset of glucose deprivation. NGF, bFGF, and IGFs also protected neurons against damage caused by exposure to a hypoxic environment. By stabilizing intraneuronal calcium levels within a window of concentrations conducive to neuronal survival, growth factors can protect neurons against the damaging effects of ischemia-like insults. Because ATP levels are expected to be reduced under ischemia-like conditions, we determined whether the growth factors would protect neurons against a more selective reduction in ATP levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth factors protect neurons against excitotoxic/ischemic damage by stabilizing calcium homeostasis. 824 11

Basic fibroblast growth factor (bFGF) has been shown to have neuroprotective effects in animal models of ischemia. To determine whether bFGF is protective against seizure-induced brain damage, we administered bFGF through osmotic pumps prior to, and after treatment with kainic acid (KA). Recombinant bFGF, CS23, a modified human bFGF, was infused into the lateral ventricles in rats for 2 days before and 5 days after the injection of KA. Control rats received equal volumes of phosphated saline over the same period of time. Infusion of 5 micrograms/ml of bFGF (0.5 microliter/h) did not modify the latency and duration of seizures induced by intraperitoneal injections of KA. However, bFGF prevented cell loss in the hippocampus in 80% of the rats. In control rats, cell loss in the hippocampus was found in all rats. These results indicate that bFGF has a substantial neuroprotective effect.
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PMID:Neuroprotective effect of chronic infusion of basic fibroblast growth factor on seizure-associated hippocampal damage. 828 47

We have established an in vitro model of ischemia incorporating the combination of anoxia with glucose deprivation, which is toxic to PC12 cells. In this model, nerve growth factor (NGF), basic fibroblast growth factor (bFGF), and epidermal growth factor (EGF) improve PC12 cell survival. K252a, a specific inhibitor of NGF-induced trk p140 autophosphorylation, did not alter the neuroprotection provided by EGF or bFGF, yet it completely abolished the protection provided by NGF. Activation of protein kinase A (PKA) with dibutyryl-cAMP also protected during ischemia, although it was not additive with the effect provided by growth factors. Furthermore, growth factors protected a PKA-deficient mutant as effectively as the parental cell line; thus, activation of PKA is protective against ischemia but is not necessary for the action of peptide growth factors. Neither the stimulation of protein kinase C (PKC) with acute phorbol ester treatment nor the downregulation of PKC with chronic high-dose phorbol ester treatment resulted in an altered response to growth factors in either the PC12 wild type or PKA-deficient mutant. Thus, protection by peptide growth factors depends on neither PKA nor PKC. Furthermore, downregulation of PKC alone was protective, indicating that PKC may contribute to toxicity. Interestingly, treatment with the kinase inhibitor H-7 was neuroprotective and may have enhanced the neuroprotective effect of NGF. In contrast, staurosporine, a broadly acting kinase inhibitor, inhibited the neuroprotective effect of NGF, but not of EGF or FGF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth factors protect PC12 cells against ischemia by a mechanism that is independent of PKA, PKC, and protein synthesis. 841 Jan 84

Basic fibroblast growth factor (bFGF) is a polypeptide that promotes neuronal survival and blocks excitatory amino acid (EAA) neurotoxicity in vitro at very low concentrations. In the present study, we examined whether systemically administered bFGF could prevent neuronal damage induced by either EAAs or hypoxia-ischemia in vivo. Neuroprotective effects were examined in a neonatal model of hypoxia-ischemia (unilateral ligation of the carotid artery followed by exposure to 8% oxygen for 1.5 h) and following intrastriatal injection of N-methyl-D-aspartate (NMDA) in 7-day-old rats. Intraperitoneal administration of a single dose of bFGF (50-300 micrograms/kg) 30 min before intrastriatal injection of NMDA showed a dose-dependent neuroprotective effect. Repeated doses of bFGF (100 micrograms/kg) both before and after intrastriatal NMDA injection produced a much greater significant protective effect than a single dose administered prior to the injection. Intraperitoneal injection of single dose of 100 micrograms/kg of bFGF 30 min before hypoxia-ischemia reduced neuronal damage by 38% (p = 0.14), while administration of bFGF at a dose of 100 micrograms/kg i.p. three times, 30 min before and 0 and 30 min after hypoxia-ischemia, significantly reduced neuronal damage by 64% (p = 0.004). Systemic administration of bFGF did not change body temperature for up to 3 h. These results show that systemic administration of bFGF can exert neuroprotective effects against both NMDA-induced excitotoxicity and hypoxia-ischemia in vivo.
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PMID:Basic fibroblast growth factor protects against hypoxia-ischemia and NMDA neurotoxicity in neonatal rats. 843 14

Iron is believed to contribute to the process of cell damage and death resulting from ischemic and traumatic insults by catalyzing the oxidation of protein and lipids. Exposure of cultured rat hippocampal neurons to iron (FeSO4) caused a dose-dependent reduction in neuronal survival, which was potentiated by ascorbate. Damage to neurons was associated with a significant level of oxygen radical in the culture medium. The iron chelator desferal prevented both the neuronal degeneration caused by FeSO4 and the production of oxygen radical, demonstrating that ionic iron was responsible for the cell damage. Iron neurotoxicity was associated with an elevation of [Ca2+]i and was attenuated by NMDA receptor antagonists. Since recent findings demonstrated neuroprotective effects of growth factors in cell culture and in vivo models of ischemia, we examined the effects of growth factors on iron-induced damage. Basic fibroblast growth factor (bFGF), nerve growth factor (NGF), and insulin-like growth factors (IGF-I and IGF-II) each protected neurons against iron-induced damage. Both rat hippocampal and human cortical neurons were protected by these growth factors. Taken together, the data suggest that the neuroprotective effects of growth factors against excitotoxic/ischemic insults may result, in part, from a prevention or attenuation of oxidative damage.
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PMID:Basic FGF, NGF, and IGFs protect hippocampal and cortical neurons against iron-induced degeneration. 847 96

We examined the effects of treatment with basic fibroblast growth factor (b-FGF) on hippocampal CA1 neuronal damage following 3 min of forebrain ischemia in the gerbil. Continuous infusion of b-FGF (24 or 240 ng/day over 4 days) using an implanted osmotic minipump into the lateral ventricle prevented CA1 neuronal damage in a dose-dependent manner.
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PMID:Protective effects of basic fibroblast growth factor against hippocampal neuronal damage following cerebral ischemia in the gerbil. 848 88

Polyclonal antibodies directed against human recombinant basic fibroblast growth factor (bFGF) were used in immunohistochemical studies to localize this growth factor in normal and wounded rat skeletal muscles. bFGF immunoreactivity was found mainly in the extracellular matrix, primarily in the endomysium, including the heparin-containing basal lamina and also in the capillary basal membrane of both normal and wounded muscles, however the signal intensity was much stronger in normal muscles. After 4-hour ischemia, about 40% of skeletal muscle fibers lost their bFGF immunoreactivity. Muscles which experienced 4-hour ischemia and 24 reperfusion had only a weaker bFGF immunoreactivity. The pathological results supported the concept of destroyed cell connection and fiber necrosis in ischemia and reperfused muscles. The mechanisms involved in this reduced concentration of bFGF in wounded muscles included oxygen radical activation, inflammatory response and reduced secretion of endogenous bFGF. These results were only partially compatible with the established mitogenic role of this protein and suggested that a reduction of endogenous FGF may partly contribute to a delay in wound healing.
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PMID:Ischemia and reperfusion reduce the endogenous basic fibroblast growth factor (bF GF) in rat skeletal muscles. 857 38

Basic fibroblast growth factor (bFGF) is a polypeptide with potent trophic effects on brain neurons, glia, and endothelial cells. In the current study, we used Northern blotting, in situ hybridization, and immunohistochemical techniques to examine bFGF expression in brain following focal infarction due to permanent occlusion of the proximal middle cerebral artery in mature Sprague-Dawley rats. We found a four-fold increase in bFGF mRNA in tissue surrounding focal infarcts at 1 day after ischemia. In situ hybridization showed that this increase was found throughout several structures in the ipsilateral hemisphere, including frontoparietal, temporal, and cingulate cortex, as well as in caudoputamen, globus pallidus, septal nuclei, nucleus accumbens, and olfactory tubercle. Increased bFGF mRNA expression was associated with cells having the distinct morphological appearance of astroglia in these structures. Immunohistochemistry showed an increase in the size and number of bFGF-immunoreactive (IR) nuclei in these same structures, as well as a shift from nuclear to nuclear plus cytoplasmic localization of immunoreactivity, beginning at 1 day, and peaking at 3 days after ischemia. Double immunostaining identified bFGF-IR cells as astroglia in these structures. (An exception was the piriform cortex, in which both increased bFGF mRNA levels and increased bFGF-IR was found in neurons at 1 day after ischemia). Overall, the peak of increased bFGF expression preceded the peak in expression of the astroglial marker GFAP within the ipsilateral hemisphere. Increased bFGF expression may play an important role in the glial, neuronal, and vascular changes occurring after focal infarction.
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PMID:Increased expression of basic fibroblast growth factor (bFGF) following focal cerebral infarction in the rat. 880 11


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