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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipid and carbohydrate metabolism abnormalities are reviewed with particular emphasis on the role of insulin and interrelationships between carbohydrate and lipid metabolism. The pathogenesis of atherosclerosis is discussed in terms of the association of abnormal circulating insulin levels. Some of the conditions associated with abnormal insulin levels and atherosclerosis are diabetes mellitis, hypertriglyceridemia, obesity, uremia, and oral contraceptive use. There is evidence that a proportion of subjects who have atherosclerosis or at risk have elevated circulating insulin levels. There is also increasing evidence that the arterial wall is an insulin-sensitive tissue. More women with myocardial infarction take oral contraceptives than controls do. Those who take the pill have 9 times the risk of others to develop cerebral ischemia or thrombosis. Many oral contraceptives cause abnormalities in glucose tolerance associated with elevated plasma insulin levels, and a degree of insulin resistance is induced. A number of the metabolic consequences of the pill may be caused by the elevated insulin levels.
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PMID:The relationship of abnormal circulating insulin levels to atherosclerosis. 85 12

Excitatory amino acids are implicated in the development of neuronal cell damage following periods of reversible cerebral ischemia or insulin-induced hypoglycemic coma. To explore the importance of glutamate receptor activation in the posthypoglycemic phase, we exposed rats to 20 min of insulin-induced severe hypoglycemia. The rats were treated immediately after the hypoglycemic insult with four regimes of glutamate receptor antagonists: (1) the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propriate)-receptor antagonist NBQX [2.3-dihydroxy-6-nitro-7-sulfamoyl-benzo (F) quinoxaline] given as a bolus dose of 30 mg.kg-1 i.p., followed by an i.v. infusion of 225 micrograms.kg-1.min-1 for 6 h; (2) the non-competitive NMDA-receptor antagonist, dizocilpine (MK-801) 1 mg.kg-1 given i.v.; (3) a combined NBQX treatment, (a bolus dose of 10 mg.kg-1 i.p., followed by an i.v. infusion of 225 micrograms.kg-1.min-1 for 6 h), with dizocilpine 0.33 mg.kg-1 given twice i.p. at 0 and 15 min after recovery and (4) the competitive NMDA-receptor blocker CGP 40,116 [D-(E)-2-amino-4-methyl-5-phosphono-3- pentenoic acid] 10 mg.kg-1 given i.p. In the striatum, all glutamate receptor blockers significantly decreased neuronal damage by approximately 30%. An approximately 50% decrease in neuronal damage was demonstrated in neocortex and hippocampus following the combined treatment with NBQX and dizocilpine, while protection was variable following the treatment with a single glutamate-receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebral protection by AMPA- and NMDA-receptor antagonists administered after severe insulin-induced hypoglycemia. 136 58

Perioperative GIK therapy has been advocated to ensure adequate energy substrate levels during cardiac surgery. However, hyperglycemia should be avoided because it may worsen neurologic outcome after cerebral ischemia. A prospective, randomized, clinical comparison was performed between two prebypass infusion regimens in 32 elective nondiabetic CABG patients. Sixteen patients (GIK group) received glucose, 0.6 g/kg/h, insulin, 0.12 U/kg/h, and KCl, 0.12 mmol/kg/h, from the induction of anesthesia to the start of CPB; while the remaining 16 patients (R group) received only Ringer's acetate. The pump prime was glucose free and a blood cardioplegia technique was used in both groups. No differences were found between the groups with regard to myocardial injury; the CK-MB enzyme fractions were elevated to a similar degree and the frequency of postoperative ECG changes were similar in both groups. Likewise, there were no differences in hemodynamic changes, need for inotropic support, arrhythmia frequency, or duration of ICU stay. The GIK patients had higher blood glucose (P < 0.05) and insulin levels (P < 0.01); blood glucose increased to 12.4 +/- 5.4 mmol/L (mean +/- SD) at cannulation, with a drop after starting bypass. Interindividual variation in GIK patients was great, with glucose values ranging between 20.1 mmol/L at cannulation to 2.0 mmol/L after starting CPB. A hyperglycemic response was seen in both groups during rewarming: 15.0 +/- 4.2 and 15.0 +/- 3.1 mmol/L in GIK and R patients, respectively. It is concluded that prebypass GIK infusion had no clinical benefits for elective CABG patients as compared to Ringer's acetate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prebypass glucose-insulin-potassium infusion in elective nondiabetic coronary artery surgery patients. 142 Oct 62

The pathogenesis of fetal brain damage caused by acute maternal hypoglycemia was investigated experimentally in cats: profound hypoglycemia (blood glucose concentration: less than 30 mg/dl) was induced in 12 pregnant cats at various stages of gestation by intravenous bolus injections of insulin. Maximal hypoglycemia was attained within 2-3 h, although the grade and duration in individual cats varied. The EEGs of all of seven maternal cats examined showed an increased frequency of slow high-voltage waves as hypoglycemia progressed, eventually becoming flat in 3 for a maximum period of 20 min. Some fetuses showed severe neuropathological changes, such as infarction or intrauterine death. Subventricular softening, cortical hemorrhage and ischemic neuronal changes also occurred, being distributed symmetrically in the parasagittal areas of the cerebrum, basal ganglia, thalamus and tegmentum of the brainstem. In general, these pathological changes were more marked in fetuses and neonates than in the maternal cats, in which only ischemic neuronal changes were present, and may have been due to fetal systemic hypotension and cerebral ischemia induced by hypoglycemia. In maternal cats, the distribution of neurons showing ischemic changes was widest in the cerebral cortex, and some were also present in the dentate gyri of the hippocampus. Moreover, ultrastructural examination of the ischemic neurons in maternal cats, unlike those of the fetuses, showed no mitochondrial swelling. Therefore, the distribution and ultrastructural nature of the ischemic neurons found in the maternal cats were considered to be characteristic of hypoglycemia, as proposed by Agardh et al. (1980).
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PMID:Pathological effects of maternal hypoglycemia on fetal development in cats. 163 33

The present study was designed to examine the effect of blood glucose level on survival and pathologic changes of the cortical neuronal cells during and after three-hour incomplete cerebral ischemia, which was induced by bilateral carotid artery ligation in spontaneously hypertensive rats (SHRs). Blood glucose levels were varied by intraperitoneal infusion of 50% glucose (hyperglycemia) or insulin with hypertonic saline (hypoglycemia) or hypertonic saline (normoglycemia). None of the hyperglycemic or normoglycemic animals died during three-hour ischemia, whereas 45% of hypoglycemic animals died (p greater than 0.001). The survival rate for twenty-four hours after recirculation was in the following ascending order: hypoglycemia, normoglycemia, and hyperglycemia. Neither hypoglycemia nor hyperglycemia (38-392 mg/dL) in nonischemic animals developed any morphologic changes in the cerebral cortex. However, both the ischemic and recirculated brains showed various degrees of histologic changes such as shrinkage of the neuronal cells with cytoplasmic vacuoles, perineuronal edema, and swelling of neuropils. Such ischemic damage of the brain was more marked in hypoglycemic animals than in hyperglycemic or normoglycemic ones during ischemia, as well as one hour after recirculation. The results suggest that cerebral ischemia and its outcome become more deleterious in hypoglycemic than in normoglycemic and hyperglycemic states. On the other hand, hyperglycemia is not necessarily a disadvantage in acute cerebral ischemia with or without reperfusion in this model.
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PMID:Effect of blood glucose level in acute cerebral ischemia in spontaneously hypertensive rats--survival and brain pathology. 186 14

Experimental and clinical studies have revealed a worsened neurologic outcome after cerebral ischemia in hyperglycemic subjects, including hyperglycemic diabetic subjects. A possible therapy to reduce the magnitude of ischemic brain injury in diabetic subjects would be to use an insulin infusion to reduce brain glucose concentrations to values found in those who are normoglycemic and non-diabetic. The present study, using hyperglycemic diabetic rats, examined the effect of an insulin infusion on plasma and brain glucose concentrations to determine their relationship while plasma glucose concentrations decreased. In addition, plasma and brain glucose concentrations were compared to those in diabetic and nondiabetic rats treated with saline. Saline had no effect on the plasma or brain glucose concentrations in the diabetic rats or nondiabetic rats. The saline-treated diabetic rats had increased plasma and brain glucose concentrations as well as an increased brain-to-plasma glucose ratio when compared to the saline-treated nondiabetic rats. When an insulin infusion was used in diabetic rats to decrease plasma glucose to nondiabetic levels over approximately 2 h, the brain glucose concentration decreased. However, the brain-to-plasma glucose ratio remained at the "diabetic" value, so that the brain glucose concentration tended to remain increased when compared to normoglycemic, nondiabetic rats. We conclude that if these results are applicable to humans, measurement of plasma glucose in diabetic patients will underestimate the amount of glucose in the brain and this relationship will not be influenced by acute insulin therapy.
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PMID:The effects of insulin infusion on plasma and brain glucose in hyperglycemic diabetic rats. A comparison with placebo-treated diabetic and nondiabetic rats. 192 77

The effects of magnesium, an endogenous inhibitor of calcium entry into neurons, upon ischemic brain damage were investigated using a well-characterized model of focal cerebral ischemia in rats. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride transcardiac perfusion 48 h after middle cerebral artery (MCA) occlusion. The area of ischemic damage was quantified by image analysis in coronal sections taken every 0.5 mm. MgCl2 (1 mmol/kg) was injected intraperitoneally just after MCA occlusion and again 1 h later. Posttreatment with MgCl2 (16 control and 16 treated rats) significantly reduced the cortical infarct volume. Compensation for the hyperglycemic effect of MgCl2 with insulin (17 rats) further reduced the infarct volume in the neocortex. No systemic effects of either treatment could account for the observed neuroprotection.
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PMID:Reduction of infarct volume by magnesium after middle cerebral artery occlusion in rats. 193 80

Although hyperglycemia has been shown to consistently exacerbate ischemia brain injury following global or diffuse cerebral ischemia, the effect of hyperglycemia in unilateral focal cerebral ischemia remains controversial. Recent advances in thrombolytic therapy have enhanced the clinical significance of postischemic reperfusion. We studied the effect of plasma glucose on ischemic brain injury in a newly developed focal cerebral ischemia-reperfusion model. Rats allowed free access to food until ischemic insult developed intra- and postischemic hyperglycemia and cortical infarction. Rats fasted for 24 hours had blunted hyperglycemic responses. Infarct volumes were correspondingly smaller. The protective effect of fasting was partially abolished by glucose loading during ischemia to induce intra-ischemic hyperglycemia. Glucose loading immediately or 3 hours after focal cerebral ischemia did not significantly alter the protective effect of fasting. Insulin treatment in fed rats before ischemia also reduced hyperglycemic responses and infarct volume. Timing of insulin treatment was also critical in the reduction of ischemic injury. These findings indicate that plasma glucose during the period of ischemia is an important determinant of brain injury in focal cerebral ischemia-reperfusion and there is a therapeutic window for normalization of plasma glucose to be efficacious.
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PMID:Effect of plasma glucose on infarct size in focal cerebral ischemia-reperfusion. 174 69

Although it has been well established that hyperglycemia increases cerebral damage following transient cerebral ischemia, its effect on permanent focal ischemia is controversial. We hypothesized that other factors associated with hyperglycemia, such as plasma insulin, may alter the brain's response to hyperglycemia. The objective of this study was to determine if hyperglycemia changes infarction size following 8 hr of middle cerebral artery occlusion in the anesthetized cat and to examine if changes in plasma insulin levels alter hyperglycemia's effects. Infarct size in hyperglycemic cats with increased plasma insulin (38.3 +/- 8.4, mean +/- SE) or in hyperglycemic cats without increased plasma insulin (30.5 +/- 7.6%) was not significantly different from that of ischemic controls (33.8 +/- 2.8%). However, the variability in infarct size tended to be greater (P = 0.0647) among all hyperglycemic cats compared to control animals. The source of the variability is unknown, but this observation is dependent on the exact nature of the focal ischemic insult (i.e., degree of collateral blood supply) and that this effect may vary greatly from individual to individual within a population.
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PMID:Focal cerebral infarction in cats in the presence of hyperglycemia and increased insulin. 208 16

Seizures are a documented complication to cerebral ischemia. After 10 min of forebrain ischemia in rats, preischemic hyperglycemia invariably leads to severe, most often fatal epileptic attacks. This outcome is related to the exaggerated lactic acidosis, which has been suggested as a possible contributor to severe membrane changes and widespread edema. To find out if circulating hormones or plasma energy substrates modulate this additive damage caused by the hyperglycemia, plasma concentrations of of corticosterone, epinephrine, norepinephrine, dopamine, glucagon, insulin, glucose, free fatty acids (FFA), 3-hydroxybutyrate, and acetoacetate were measured before and in the early recirculation period after 15 min of forebrain ischemia in the rat. Plasma corticosterone levels did not differ between the normo- and hyperglycemic groups. Although not significantly different from control, the catecholamine levels showed a tendency to be higher in the hyperglycemic groups. Therefore, because catecholamines have been reported to have a protective effect during ischemia the present result cannot explain why hyperglycemia aggravates the ischemic damage. Insulin levels seemed to increase during ischemia but not significantly. Levels quickly returned to normal after 30 min of recirculation. FFA concentrations were reduced after the induction of ischemia and appeared lower in all hyperglycemic groups. The level of one of the ketone bodies, 3-hydroxybutyrate, showed a significant decrease in hyperglycemic ischemia in all groups compared with normoglycemic ischemia. The same tendency was seen for acetoacetate. Results are compatible with a protective role of ketone bodies in ischemia. It is concluded that among the hormones and substrates studied only the ketone body concentrations qualify as a modulator of the exaggerated brain damage after ischemia in hyperglycemic subjects.
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PMID:Ischemia in normoglycemic and hyperglycemic rats: plasma energy substrates and hormones. 211 Apr 23


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