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

We compared the effects of glucose injection with those of saline or mannitol on ischemic brain damage and brain water content in a four-vessel occlusion (4-VO) rat model, which simultaneously causes severe forebrain ischemia and moderate hindbrain ischemia. Glucose given before onset of ischemia was followed by severe brain injury, with necrosis of the majority of neocortical neurons and glia, substantial neuronal damage throughout the remainder of forebrain, and severe brain edema. By comparison, saline injection before forebrain ischemia resulted in only scattered ischemic damage confined to neurons and no change in the brain water content. Mannitol injection before 4-VO or D-glucose injection during or after 4-VO produced no greater forebrain damage than did the saline injection. Morphologic damage in the cerebellum, however, was increased by D-glucose injection given either before or during 4-VO. The results demonstrate that hyperglycemia before severe brain ischemia or during moderate ischemia markedly augments morphologic brain damage.
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PMID:Moderate hyperglycemia augments ischemic brain damage: a neuropathologic study in the rat. 689 Jan 57

To identify the mechanism by which hyperglycemia impairs recovery after cerebral ischemia, cortical blood flow (CBF), cortical metabolic rate for oxygen (CMRO2), and the cortical phosphorylation rate for glucose (CPRg1c) were measured in rats 1 h after a global ischemic insult of the brain. A control group remained hyperglycemic after ischemia. The experimental group received insulin which reduced plasma glucose during the period of recirculation after ischemia. Thus, the brains of both groups were hyperglycemic before and during ischemia. The CMRO2 after ischemia was higher in insulin-treated rats than in hyperglycemic rats (250 vs 168 mumol . 100 g-1 . min-1) while the CPRg1c was lower (22 vs 58 mumol . 100 g-1 . min-1). We conclude that glucose-induced inhibition of oxygen consumption in brain contributes to the impaired recovery after ischemia.
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PMID:Hyperglycemic ischemia of rat brain: the effect of post-ischemic insulin on metabolic rate. 704 25

Hyperglycemia severely impairs the outcome from cerebral ischemia. In order to sort out whether impaired brain ion homeostasis contributes extracellular "K+], [Ca++], and [H+] concentrations, [K+]e, [Ca++]e and [H+]e, of the brain cortex, as well as the EEG, were monitored during and after 10 minutes of complete cerebral ischemia in normo- and hyperglycemic rats. In both groups, the EEG-activity disappeared in 10-20 seconds of ischemia, at a time when [K+]e, [Ca++]e and [H+]e started to increase. After about 1.5 min, [K+]e showed an abrupt increase and [Ca++]e a steep decrease in the normoglycemic group. In the hyperglycemic group the same event took place after about 3 min of ischemia. pHe decreased to 6.6 and 6.1 in the normoglycemic and hyperglycemic group, respectively. Following the ischemic episode [K+]e reached pre-ischemic level after 4 min, [Ca++]e after 13 min, and [H+]e after 30 min in both groups. Recovery of the EEG, however, was clearly different in the 2 groups. EEG-activity reappeared later in the hyperglycemic group and showed after one hour a pattern of burst-suppression activity while the normoglycemic group showed asynchronous activity resembling the control pattern. It is concluded that high glucose content in brain prior to ischemia - and hence lower brain pH during ischemia - does not interfere with the return of normal extracellular ion composition after cerebral ischemia, whereas the return and pattern of EEG activity is severely affected.
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PMID:Brain extracellular ion composition and EEG activity following 10 minutes ischemia in normo- and hyperglycemic rats. 723 72

This study explores the influence of severe lactic acidosis in the ischemic rat brain on postischemic recovery of the tissue energy state and neurophysiological parameters. Severe incomplete brain ischemia (cerebral blood flow below 5% of normal) was induced by bilateral carotid artery clamping combined with hypovolemic hypotension. We varied the production of lactate in the tissue by manipulating the blood glucose concentrations. A 30-min period of incomplete ischemia induced in food-deprived animals caused lactate to accumulate to 15-16 mumol g-1 in cortical tissue. Upon recirculation these animals showed: (1) a considerable recovery of the cortical energy state as evaluated from the tissue concentrations of phosphocreatine, ATP, ADP, and AMP; and (2) return of spontaneous electrocortical activity as well as of somatosensory evoked response (SER). In contrast, administration of glucose to food-deprived animals prior to ischemia caused an increase in tissue lactate concentration to about 35 mumol g-1. These animals did not recover energy balance in the tissue and neurophysiological functions did not return. In other experiments the production of lactate during 30 min of complete compression ischemia was increased from about 12 mumol g-1 (normoglycemic animals) to 20-30 mumol g-1 by preischemic hyperglycemia and, in separate animals, combined hypercapnia. The recovery of the cortical energy state upon recirculation was significantly poorer in hyperglycemic animals. It is concluded that a high degree of tissue lactic acidosis during brain ischemia impairs postischemic recovery and that different degrees of tissue lactic acidosis may explain why severe incomplete ischemia, in certain experimental models, is more deleterious than complete brain ischemia.
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PMID:Brain lactic acidosis and ischemic cell damage: 1. Biochemistry and neurophysiology. 732 45

Hyperglycemic rats were exposed to 10 min of complete cerebral ischemia. Rats with 26 mM (range 23-27 mM) plasma glucose levels died. Rats with the same degree of hyperglycemia, treated after ischemia with pentobarbital (75-95 mg/kg) or diazepam (10-13 mg/kg), survived the observation period of 21 days and recovered, albeit incompletely. The same treatment given to rats with higher degrees of hyperglycemia did not prevent death. It is concluded that postischemic treatment with anticonvulsive drugs may improve clinical restitution from ischemia in moderately hyperglycemic rats.
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PMID:Improvement of restitution from cerebral ischemia in hyperglycemic rats by pentobarbital or diazepam. 741 8

Release of angiogenic factors in response to the ischaemic retina is currently the most favoured hypothesis for the pathogenesis of proliferative diabetic retinopathy. Reducing the stimulus for angiogenesis by destroying the ischaemic retina also forms the basis of the most effective treatment of diabetic retinopathy by photocoagulation. Though ischaemia is undoubtedly important for neovascularization, there is recent evidence which cast doubts on ischemia being the sole mechanism for diabetic retinopathy. Many clinical observations viz. the protective effects of glaucoma, myopia, unilateral carotid stenosis on diabetic retinopathy; and its worsening after cataract extraction are not adequately explained by the present hypothesis. Moreover, the recent in vitro culture studies on retinal pigment epithelial cells have suggested an alternative explanation for the effectiveness of photocoagulation in proliferative diabetic retinopathy. Furthermore, hyperglycemia has been strongly correlated with the incidence and progression of diabetic retinopathy, but has only been indirectly indicted in its pathogenesis. These facts can be integrated into a more plausible hypothesis for the pathogenesis of diabetic retinopathy. It is hypothesized that a relative reduction in intra-ocular pressure caused by persistent or intermittent hyperglycemia may be the missing link that induces certain morphological changes in the retinal pigment epithelium. These changes, in addition to the ischaemic retina, may be important for the pathogenesis of diabetic retinopathy. Such a hypothesis also explains most of the hitherto unexplained features of diabetic retinopathy.
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PMID:Pathogenesis of diabetic retinopathy--the missing link? 750 46

Nerve ischemia/hypoxia has been linked to the pathogenesis of diabetic complications. Red blood cell 2,3-diphosphoglycerate is an important regulator of peripheral tissue oxygenation; however, the relationship between 2,3-diphosphoglycerate concentration and diabetic complications has not been studied in detail. This investigation focused on the relationship between red blood cell 2,3-diphosphoglycerate and diabetic neuropathy, by measuring motor nerve conduction velocity and sciatic nerve blood flow in streptozotocin-induced diabetic rats. The effect of treatment with niceritrol, a nicotinic acid derivative that acts as a vasodilator and reduces serum lipid concentrations, on 2,3-diphosphoglycerate concentration and diabetic neuropathy was also examined. Untreated diabetic rats had significantly lower concentrations of red blood cell 2,3-diphosphoglycerate, higher concentrations of serum total cholesterol and triglyceride, as well as reduced motor nerve conduction velocity and sciatic nerve blood flow, compared to untreated normal rats. Niceritrol prevented these abnormalities without correcting hyperglycemia in diabetic rats, but had no effect on these parameters in normal rats. Red blood cell 2,3-diphosphoglycerate concentration and motor nerve conduction velocity showed a positive correlation with sciatic nerve blood flow and 2,3-diphosphoglycerate, respectively. These observations suggest that ischemia/hypoxia plays an important role in the development of diabetic neuropathy, and that niceritrol has a therapeutic effect on this condition by improving endoneurial ischemia/hypoxia.
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PMID:Niceritrol prevents the decrease in red blood cell 2,3-diphosphoglycerate and neuropathy in streptozotocin-induced diabetic rats. 754 76

We tested the hypothesis that the exacerbation of post-ischemic brain tissue injury associated with hyperglycemia in rats is due to toxic metabolism of nitric oxide. We used magnetic resonance imaging (MRI) techniques to measure neuronal and cerebrovascular injury in a 2-h transient focal cerebral ischemia model in normoglycemic and hyperglycemic rats at 3 and 24 h post-ischemia onset. We determined the effect of low dose (3 mg/kg i.p.) treatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Compared to normoglycemia, preexisting hyperglycemia increased the volume of brain tissue exhibiting hyperintensity in diffusion weighted MRI (DWI) by factors of 5.6 and 6.2 at 3 h and 24 h post-ischemia, respectively. A similar increase in tissue volumes exhibiting hyperintense signal in T2-weighted MRI (T2WI) (3.3-fold and 5.6-fold) was observed. Cerebral blood volume MRI indicated a large focal no-reflow zone in hyperglycemic rats. Treatment with L-NAME eliminated the no-reflow zone in the hyperglycemic rats, and reduced tissue volumes of DWI hyperintensity by 86% and 93% at 3 h and 24 h, respectively. Similarly, tissue volumes of T2WI hyperintensity were reduced by 80% and 94% at 3 h and 24 h, respectively. Thus, nitric oxide is an important mediator in the exacerbation of post-ischemic brain injury in hyperglycemic rats. Inhibition of nitric oxide synthase limits edema formation, improves perfusion and reduces infarct volume.
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PMID:Nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester decreases ischemic damage in reversible focal cerebral ischemia in hyperglycemic rats. 755 44

The object of the study was to find out how preischemic hyperglycemia (in normocapnic animals) or excessive hypercapnia (in normoglycemic animals) affect the calcium transient during ischemia, as this can be assessed by measurements of the extracellular calcium concentration ([Ca2+]e). To that extent, normocapnic-normoglycemic control animals were compared with animals with induced hyperglycemia or hypercapnia, all being subjected to 10 min of forebrain ischemia, the [Ca2+]e and d.c. potential being measured with ion-sensitive glass microelectrodes. Hyperglycemia and hypercapnia delayed the loss of ion homeostasis following induction of ischemia. Furthermore, both hyperglycemia and hypercapnia reduced the delay of Ca2+ extrusion upon recirculation. As a result, both hyperglycemia and hypercapnia significantly reduced the ischemic calcium transient, as this was assessed by calculating the duration of maximal calcium load of cells. The results make it less likely that aggravation of brain damage by hyperglycemia or excessive hypercapnia is related to a further derangement of cell calcium homeostasis.
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PMID:Influence of hyperglycemia and of hypercapnia on cellular calcium transients during reversible brain ischemia. 758 97

There is great concern about the health effects of cocaine use during pregnancy. Cocaine alters maternal physiology and crosses the placenta to interact with fetal tissues including the brain. Neurotoxicity, defined as structural and/or functional changes which result in a neurobehavioral deficit, is not unequivocally documented in the human. It is difficult to ascertain duration, intensity and frequency of cocaine exposure in humans as well as the effects of multiple drug use, poor nutrition, lack of prenatal care, lead exposure and infectious diseases. In addition, plasticity of the central nervous system makes the postnatal environment as important as the intrauterine milieu for the developing organism. Animal studies, which allow quantitation of drug exposure and reduction of confounding variables, suggest several possible mechanisms for neurotoxicity induced by cocaine or its active metabolites. The possible mechanisms include: alteration of sodium channel and monoamine transporter development, release of epinephrine from the adrenal medulla with subsequent hyperglycemia, vasoconstriction with subsequent hypoxia and decrease of nutrient supply, calcium ion chelation, superoxide formation or infarction following repeated ischemia and reperfusion, enzyme inhibition, reduced neurotrophic activity, altered gene expression and plasma membrane changes. Alterations in the above parameters may cause acute and reversible effects as well as chronic and permanent effects. Not all alterations in structure and function are deficits, and no single mechanism may explain a given alteration.
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PMID:Potential mechanisms of cocaine-induced developmental neurotoxicity: a minireview. 760 37


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