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

The renal growth hormone--insulin-like growth factor-I system in acute ischemic renal failure. Recovery from acute tubular necrosis (ATN) is accelerated by IGF-I therapy. Furthermore, the local renal growth hormone-IGF-I system may participate in the natural repair. We examined the IGF-I system in rat kidneys subjected to 60 minute ischemia compared to sham operated controls. Two days after injury, growth hormone receptor mRNA and IGF-I mRNA levels fell approximately 9 to 33% of control values. This was associated with a reduction in kidney immunoreactive IGF-I levels. In contrast, IGF-I receptor mRNA abundance was unchanged. However, plasma membrane IGF-I receptor binding on day 2 and day 7 was near double the control values (P < 0.01). Scatchard analysis revealed a near twofold increase in receptor number. Since receptor mRNA levels were unchanged, this implies receptor protein up-regulation. In contrast to unchanged IGF-I receptor mRNA levels, the abundance of mRNA levels of insulin-like growth factor binding proteins (IGFBP) -2, -3, -4 and -5 fell approximately 14 to 62% of control levels day 2 after injury (P < 0.05), suggesting reduced IGFBP production. Thus, the renal response to ischemic ATN, namely, low IGFBP mRNA levels and high IGF-I receptor number, may function to increase IGF-I bioavailability and thereby enhance the reparative actions of local and circulating IGF-I in ischemic ATN.
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PMID:Renal growth hormone--insulin-like growth factor-I system in acute renal failure. 754 60

Binding of 125I-insulin-like growth factor-1 (125I-IGF-1) to rat brain slices was studied after 15 min of two-vessel occlusion ischemia and 1 h to 4 days of recirculation. Ligand binding in the hippocampus increased at 6 h post ischemia in the CA1 and CA3 regions and the dentate gyrus, suggesting that the IGF-1 receptors were up-regulated, while no change was seen in neocortex and striatum. Intracerebroventricular injections of IGF-1 (2 micrograms) prior to and after transient cerebral ischemia did not reduce neuronal damage. The increased up-regulation on IGF-1 receptors and the absence of neuroprotection by IGF-1 suggest that the intracellular signal transduction chain activated by the IGF-1 receptor may be interrupted.
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PMID:Changes in insulin-like growth factor 1 receptor density after transient cerebral ischemia in the rat. Lack of protection against ischemic brain damage following injection of insulin-like growth factor 1. 836 Feb 96

Prolonged cold ischemia time and the generation of free oxygen radicals during reperfusion are risk factors for allograft arteriosclerosis. Growth factors are the main pro-proliferative mediators of smooth muscle cells in classical and in allograft arteriosclerosis. Superoxide dismutase is an enzyme that catalyzes the dismutation of superoxide anions into hydrogen peroxide. This study was designed to investigate which smooth muscle cell growth factor contribute to the formation of arteriosclerosis in syngenic vascular grafts with prolonged ischemia time, and whether perioperative intravenous administration of recombinant human superoxide dismutase (rh-SOD) prevents arteriosclerosis in these grafts. DA aortas were transplanted into DA recipients. One group of transplants was made with a short ex vivo ischemia time (15 min), while the other group transplant grafts was stored for 24 hr in cold saline. In addition to morphometric quantitation of the histological alterations, RNA isolated from grafts with short cold ischemia time in a semiquantitative polymerase chain reaction specific for various known smooth muscle cell growth factors. Syngeneic grafts with prolonged cold ischemia time showed severe intimal thickening and prominent medical necrosis, which were not seen in control groups. Approximately 3-fold levels of insulin-like growth factor-1 were found in ischemic syngeneic grafts compared with non-ischemic syngenic grafts, whereas epidermal growth factor levels were slightly lower. No changes in other growth factor mRNAs were found. Perioperative treatment with rh-SOD did not have significant effect on the extent of intimal thickening nor on the intensity of medial necrosis in grafts with prolonged ischemia time, and administration of rh-SOD did not change the expression level of insulin-like growth factor-1 in the grafts, either.
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PMID:Lack of effect of recombinant human superoxide dismutase on cold ischemia-induced arteriosclerosis in syngeneic rat aortic transplants. 862 79

The insulin-like growth factor (IGF) system has a role in repair following hypoxic-ischemic injury in many tissues including the brain. To study the involvement of the IGF system following head trauma, we used a rat contusion model, which produces a focal lesion of the cerebral cortex. Molecules in the IGF system were analyzed using in situ hybridization at different times following impact. We observed a dramatic up-regulation of insulin-like growth factor binding protein-2 (IGFBP-2) mRNA in cortical areas adjacent to the injury 24 h after impact, with a peak 10-fold increase engaging most of the ipsilateral cortex 2 and 3 days post-contusion. Seven days after the contusion, IGFBP-2 expression was only moderately up-regulated and again concentrated around the injury. IGFBP-4 mRNA levels increased 4-fold ipsilateral to the site of injury, with retained pattern of cortical expression. IGFBP-3, IGFBP-5 and IGFBP-6 mRNA all displayed distinct expression patterns in the brain but no significant changes were observed following injury. In contrast, IGF-1 mRNA levels were very low prior to contusion, but increased markedly at the site of injury with a peak at day 3. We were unable to detect any changes in the type 1 IGF-receptor or IGF-2 mRNA following contusion. The neuropeptide cholecystokinin (CCK) mRNA was clearly up-regulated following contusion, with an even distribution over the ipsilateral cortex. The expression pattern of molecules in the IGF system post-contusion differs in part to changes observed following hypoxic-ischemia or ischemia alone, perhaps reflecting different regulatory mechanisms depending on the type of injury.
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PMID:Increase of insulin-like growth factor (IGF)-1, IGF binding protein-2 and -4 mRNAs following cerebral contusion. 879 17

The effect of exogenous insulin-like growth factor (IGF)-I and growth hormone (GH) was examined in a rat model of intestinal ischemia-reperfusion (I/R). Animals were anesthetized, vascular catheters were placed, and intestinal ischemia was induced for 60 min. Thereafter, the intestine was reperfused, and rats received a primed, constant infusion of either IGF-I or GH (500 microg/rat + 500 microg/day) for the remainder of the study; control rats received an equal volume of vehicle. The plasma IGF-I concentration gradually declined after I/R in the vehicle-shock group and was reduced 30% at 48 h. GH infusion completely prevented this reduction, whereas the effect of IGF-I was intermediate. The IGF-I content in liver was increased by IGF-I (78%) and further enhanced in the GH-treated group (140%). Comparable increases were seen for the abundance of IGF-I mRNA in liver in these two treatment groups, compared to the vehicle control. In contrast, while both IGF-I and GH elevated the IGF-I content in skeletal muscle similarly (80%), no increase in IGF-I mRNA expression was observed in this tissue. Neither treatment altered the IGF-I content in small intestine. At the time tissues were sampled (48 h), the plasma concentration of glucose and corticosterone was not different among the three groups. However, plasma insulin was reduced 50% in the IGF-I-infused animals, compared to values in either the shock-GH or shock-vehicle group. These data demonstrate that chronic administration of GH and, to a lesser extent, IGF-I, after intestinal I/R maintains levels of IGF-I in the blood, liver, and muscle. Thus, adjunct treatment with these anabolic agents may help blunt the increased catabolism observed in individuals following intestinal I/R.
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PMID:Insulin-like growth factor-I and growth hormone administration in intestinal ischemia shock in the rat. 968 93

Intensive efforts are presently directed toward developing pharmacologic therapy to protect the ischemic brain. Preclinical data from animal models indicate that insulin, already available for human use, may reduce damage in both global and focal ischemia. Two kinds of mechanisms may be involved: one in which insulin interacts directly with brain tissue and one in which insulin acts indirectly by reducing peripheral blood glucose levels. Animal data indicate that part of the former, direct mechanism is mediated by insulin-like growth factor-1 receptors. The direct effect appears to predominate in global ischemia. In focal ischemia, unlike global ischemia, the effect of insulin is predominantly via peripheral hypoglycemia, because neuroprotection is largely annulled by co-administration of glucose. The two clinical counterparts of global and focal ischemic models are, respectively, cardiac arrest encephalopathy and focal ischemic stroke. Insulin use in both of these clinical situations could be evaluated in clinical trials that attempt to reduce ischemic brain damage, because insulin has a long and safe history of human use in diabetes treatment.
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PMID:Insulin, blood glucose levels, and ischemic brain damage. 974 32

The central nervous system (CNS) contains a large amount of zinc; a substantial fraction of it is located inside synaptic vesicles of glutamatergic terminals in chelatable forms and released in a calcium-dependent manner with intense neuronal activity. Recently, it has been shown that excessive zinc influx can kill neurons in rats subjected to transient forebrain ischemia. On the other hand, severe depletion of zinc has been also reported to induced cell death in certain nonneuronal cells. Since decreases in tissue zinc have been associated with Alzheimer's disease (AD) and senile macular degeneration, we examined whether depletion of intracellular zinc with a zinc chelator can directly induce neuronal death in mouse cortical cultures. Exposure of cortical cultures to a cell-permeant zinc-chelator, N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine (TPEN, 0.5-3.0 microM) induced gradually developing neuronal degeneration accompanied by various features of apoptosis: cell body shrinkage, nuclear condensation and fragmentation, and internucleosomal DNA breakage. At higher concentrations, TPEN induced additional glial cell death. TPEN-induced cell death was completely blocked by coaddition of zinc. Addition of a protein synthesis inhibitor cycloheximide as well as a caspase inhibitor carbobenzoxy-valyl-alanyl-aspartyl-fluoromethyl ketone (zVAD-fmk) markedly attenuated TPEN-induced neuronal death. On the other hand, brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), phorbol 12-myristate 13-acetate (PMA), high K+, or an antioxidant, trolox, did not show any protective effect. The present results demonstrated that depletion of intracellular zinc induces protein synthesis-dependent neuronal apoptosis in cortical culture. Combined with the findings that extracellular zinc may promote extracellular beta-amyloid (A beta) aggregation and that total tissue zinc is reduced in AD, present results suggest a possibility that redistribution of zinc from intracellular to extracellular space may synergistically contribute to neuronal apoptosis in AD.
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PMID:Depletion of intracellular zinc induces protein synthesis-dependent neuronal apoptosis in mouse cortical culture. 987 67

For the past decade, an attempt has been made by many research groups to define the roles of the growing number of Bcl-2 gene family proteins in the apoptotic process. The Bcl-2 family consists of pro-apoptotic (or cell death) and anti-apoptotic (or cell survival) genes and it is the balance in expression between these gene lineages that may determine the death or survival of a cell. The majority of studies have analysed the role/s of the Bcl-2 genes in cancer development. Equally important is their role in normal tissue development, homeostasis and non-cancer disease states. Bcl-2 is crucial for normal development in the kidney, with a deficiency in Bcl-2 producing such malformation that renal failure and death result. As a corollary, its role in renal disease states in the adult has been sought. Ischaemia is one of the most common causes of both acute and chronic renal failure. The section of the kidney that is most susceptible to ischaemic damage is the outer zone of the outer medulla. Within this zone the proximal tubules are most sensitive and often die by necrosis or desquamate. In the distal nephron, apoptosis is the more common form of cell death. Recent results from our laboratory have indicated that ischaemia-induced acute renal failure is associated with up-regulation of two anti-apoptotic Bcl-2 proteins (Bcl-2 and Bcl-XL) in the damaged distal tubule and occasional up-regulation of Bax in the proximal tubule. The distal tubule is a known reservoir for several growth factors important to renal growth and repair, such as insulin-like growth factor-1 (IGF-1) and epidermal growth factor (EGF). One of the likely possibilities for the anti-cell death action of the Bcl-2 genes is that the protected distal cells may be able to produce growth factors that have a further reparative or protective role via an autocrine mechanism in the distal segment and a paracrine mechanism in the proximal cells. Both EGF and IGF-1 are also up-regulated in the surviving distal tubules and are detected in the surviving proximal tubules, where these growth factors are not usually synthesized. As a result, we have been using in vitro methods to test: (i) the relative sensitivities of renal distal and proximal epithelial cell populations to injury caused by mechanisms known to act in ischaemia-reperfusion; (ii) whether a Bcl-2 anti-apoptotic mechanism acts in these cells; and (iii) whether an autocrine and/or paracrine growth factor mechanism is initiated. The following review discusses the background to these studies as well as some of our preliminary results.
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PMID:Bcl-2 genes and growth factors in the pathology of ischaemic acute renal failure. 1036 Dec 61

Phosphate-activated glutaminase (PAG) activity decreases markedly in the early period of ischemia. The decrease of the enzyme activity is reversible if the ischemic period is relatively short, but it becomes irreversible after 90 minutes of ischemia. The deterioration is a functional damage of the retinas caused by ischemia. We studied effects of growth factors and neurotrophic factors on protection of PAG in the ischemic and reperfused rat retinas. Before ischemia, 1 microl of growth factors or neurotrophic factors (0.1 microg/microl for insulin-like growth factor-I [IGF-I], insulin-like growth factor-II [IGF-II], brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF]; 1 microg/microl for basic fibroblast growth factor [bFGF]) were injected into the vitreous cavity of the left eyes of anesthetized Sprague Dawley rats. As a control, phosphate buffered saline was injected to the right eyes. To induce ischemia, we clamped left eyes for 90 minutes after bulbar conjunctival incision all around limbus. The rat retinas were homogenized with distilled water 1 day after reperfusion and used for PAG assay. Retinal ammonia concentration was also determined as a ischemic marker. About 80% decrease of retinal PAG activity and 50% increase of retinal ammonia concentration were observed after 90 minutes of ischemia and 1 day of reperfusion as compared with unoperated normal eyes. IGF-II, BDNF and NGF had protective effects on the retinal PAG activity, whereas IGF-I, bFGF, stable bFGF were less effective. In addition, IGF-II and BDNF suppressed elevation of retinal ammonia concentration. BDNF, NGF and IGF-II have marked effect on the protection of PAG activity in the ischemic and reperfused rat retinas, whereas bFGF, which is very effective for the protection of ischemic cell death, shows moderate effect.
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PMID:Administration of nerve growth factor, brain-derived neurotrophic factor and insulin-like growth factor-II protects phosphate-activated glutaminase in the ischemic and reperfused rat retinas. 1045 79

Severe perinatal asphyxia can lead to injury and dysfunction of the basal ganglia. Post insult administration of insulin-like growth factor-1 is neuroprotective, particularly in the striatum. Insulin-like growth factor-1 is also known to be a neuromodulator of several types of striatal neurons. The striatum comprises various phenotypic neurons with a complex neurochemical anatomy and physiology. In the present study, we examined the specificity of neuronal rescue with insulin-like growth factor-1 on different striatal neurons. Bilateral brain injury was induced in near term fetal sheep by 30 min of reversible carotid artery occlusion. A single dose of 3 microg of insulin-like growth factor-1 was infused over 1 h into the lateral ventricle 90 min following ischemia. The histological and immunohistochemical outcome were examined after 4 days recovery using paraffin tissue preparations. Insulin-like growth factor-1 treatment (n = 11) significantly reduced the percentage of neuronal loss in the striatum compared with the vehicle treated group (n = 10, 28.3+/-5.1% vs 55.5+/-17.3%, P < 0.005). Immunohistochemical studies showed that ischemia resulted in a significant loss of calbindin-28kd, choline acetyltransferase, parvalbumin, glutamate acid decarboxylase, neuronal nitric oxide synthase and neuropeptide Y immunopositive neurons, compared with sham controls. Insulin-like growth factor-1 markedly prevented the loss of calbindin-28kd (n = 7, P < 0.05), choline acetyltransferase (n = 7, P < 0.05), neuropeptide Y (n = 7, P < 0.05), neuronal nitric oxide synthase (n = 8, P < 0.05) and glutamate acid decarboxylase (n = 9, P < 0.05) immunopositive neurons, but failed to protect parvalbumin (n = 6) immunopositive neurons. The present study indicates that the therapeutic effect of insulin-like growth factor-1 in the basal ganglia is selectively associated with cholinergic and some phenotypic GABAergic neurons. These data suggest a potential role for insulin-like growth factor-1 in preventing cerebral palsy due to perinatal asphyxia.
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PMID:Selective neuroprotective effects with insulin-like growth factor-1 in phenotypic striatal neurons following ischemic brain injury in fetal sheep. 1067 Apr 51


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