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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemia is associated with the pathological changes caused by the accumulation of reactive oxygen metabolites (ROM) in cerebrovascular accident (CVA). The aim of this study was to determine red cell copper/zinc-superoxide dismutase (Cu/Zn-SOD) and catalase activities and copper and zinc concentrations both in plasma and in red cells in CVA. Cu/Zn-SOD and catalase activities of 16 patients, with an average age of 64 yr, were measured spectrophotometrically; copper and zinc concentrations were determined by atomic absorption spectrophotometer. The results showed that Cu/Zn-SOD activity was increased markedly in patients compared to the young controls and reached a peak on the d 5 of the disease, whereas the catalase activity of the patients on d 3 and d 5 were in the normal range, but higher on d 10. The enzyme activities of the elderly group were generally increased compared to the young controls. Copper and zinc concentrations showed corresponding alterations. These findings suggested that the effects of oxidative stress in CVA might be reflected in red cell and plasma parameters.
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PMID:Antioxidant status in cerebrovascular accident. 1143 77

It has recently been shown that transition metal cations Zn2+ and Cu2+ bind to histidine residues of nerve growth factor (NGF) and other neurotrophins (a family of proteins important for neuronal survival) leading to their inactivation. Experimental data and theoretical considerations indicate that transition metal cations may destabilize the ionic form of histidine residues within proteins, thereby decreasing their pK(a) values. Because the release of transition metal cations and acidification of the local environment represent important events associated with brain injury, the ability of Zn2+ and Cu2+ to bind to neurotrophins in acidic conditions may alter neuronal death following stroke or as a result of traumatic injury. To test the hypothesis that metal ion binding to neurotrophins is influenced by pH, the effects of Zn2+ and Cu2+ on NGF conformation, receptor binding and NGF tyrosine kinase (trkA) receptor signal transduction were examined under conditions mimicking cerebral acidosis (pH range 5.5-7.4). The inhibitory effect of Zn2+ on biological activities of NGF is lost under acidic conditions. Conversely, the binding of Cu2+ to NGF is relatively independent of pH changes within the studied range. These data demonstrate that Cu2+ has greater binding affinity to NGF than Zn2+ at reduced pH, consistent with the higher affinity of Cu2+ for histidine residues. These findings suggest that cerebral acidosis associated with stroke or traumatic brain injury could neutralize the Zn2+-mediated inactivation of NGF, whereas corresponding pH changes would have little or no influence on the inhibitory effects of Cu2+. The importance of His84 of NGF for transition metal cation binding is demonstrated, confirming the involvement of this residue in metal ion coordination.
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PMID:The binding of zinc and copper ions to nerve growth factor is differentially affected by pH: implications for cerebral acidosis. 1148 54

Pyruvate has a remarkable protective effect against zinc neurotoxicity. Because zinc neurotoxicity is likely one of the key mechanisms of ischemic brain injury, the neuroprotective effect of pyruvate was tested in a rat model of transient forebrain ischemia. Control experiments in mouse cortical culture showed that pyruvate almost completely blocked zinc toxicity but did not attenuate calcium-overload neuronal death. Adult rats subjected to 12 min forebrain ischemia exhibited widespread zinc accumulation and neuronal death throughout hippocampus and cortex 72 hr after reperfusion. However, rats injected intraperitoneally with sodium pyruvate (500-1000 mg/kg) within 1 hr after 12 min forebrain ischemia showed almost no neuronal death. In addition, the mortality was markedly decreased in the pyruvate-protected groups (3.8%) compared with the NaCl-injected control group (58.1%). The neuroprotective effect persisted even at 30 d after the insult. The spectacular protection without noticeable side effects makes pyruvate a promising neuroprotectant in human ischemic stroke.
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PMID:Protection by pyruvate against transient forebrain ischemia in rats. 1158 1

Oxidative stress generated during stroke is a critical event leading to blood-brain barrier (BBB) disruption with secondary vasogenic edema and hemorrhagic transformation of infarcted brain tissue, restricting the benefit of thrombolytic reperfusion. In this study, the authors demonstrate that ischemia-reperfusion-induced BBB disruption in mice deficient in copper/zinc-superoxide dismutase (SOD1) was reduced by 88% ( P < 0.0001) and 73% ( P < 0.01), respectively, after 3 and 7 hours of reperfusion occurring after 1 hour of ischemia by the inhibition of matrix metalloproteinases. Accordingly, the authors show that local metalloproteinase-generated proteolytic imbalance is more intense in ischemic regions of SOD1 mice than in wild-type litter mates. Moreover, active in situ proteolysis is, for the first time, demonstrated in ischemic leaking capillaries that produce reactive oxygen species. By showing that oxidative stress mediates BBB disruption through metalloproteinase activation in experimental ischemic stroke, this study provides a new target for future therapeutic strategies to prevent BBB disruption and potentially reperfusion-triggered intracerebral hemorrhage.
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PMID:Matrix metalloproteinase inhibition prevents oxidative stress-associated blood-brain barrier disruption after transient focal cerebral ischemia. 1174 Feb

Hypertension is the most common medical complication of pregnancy in South Africa and a major cause of maternal and perinatal morbidity and mortality worldwide. At King Edward VIII Hospital in Durban, 18% of all admissions to the obstetric unit have some degree of high blood pressure. Hypertension in its most severe form produces convulsions, proteinuria, and edema and may lead to fetal and maternal death. High-risk groups for preeclampsia are teenage mothers, primigravidas, and women with a history of elevated blood pressure, previous preeclampsia, molar pregnancies, multiple pregnancies, or hydrops fetalis. Methods used to prevent preeclampsia include a low-salt diet supplemented with calcium, magnesium, zinc, fish, and pharmacological manipulation. In developing countries, prevention and detection of preeclampsia is difficult since women seek antenatal care late in their pregnancies. In Durban, the average gestational age at first antenatal attendance is 28 weeks, and 80% of patients presenting with eclampsia have defaulted antenatal care. Treatment includes admission to hospital to establish the etiology of the hypertension and maternal renal function tests . Fetal condition is a sensitive index of hypertension and is judged by 1) clinical evidence of fetal growth, 2) weekly antepartum cardiotocography, and 3) ultrasonographic screening. Patients are managed according to three clinical groups: 1) those identified before 36 weeks, 2) those identified after 36 weeks, and 3) patients in hypertensive crisis. Dihydralazine is the drug of choice for imminent eclampsia. If the patients has a ripe cervix, delivery is induced with 6-8 hours. Steroid contraception use in the older hypertensive patient should be avoided because of possible development of atherosclerosis and stroke. Puerperal tubal ligations in the hypertensive patient ought to be avoided because of the risks of thromboembolic phenomena and pulmonary embolism. Methyldopa is the treatment of choice in cases of moderate to severe hypertension. Intravenous dihydralazine is relatively safe for the rapid reduction of high blood pressure.
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PMID:Coping with hypertension in pregnancy. 1234 38

Radiation hazards in outer space present an enormous challenge for the biological safety of astronauts. A deleterious effect of radiation is the production of reactive oxygen species, which result in damage to biomolecules (e.g., lipid, protein, amino acids, and DNA). Understanding free radical biology is necessary for designing an optimal nutritional countermeasure against space radiation-induced cytotoxicity. Free radicals (e.g., superoxide, nitric oxide, and hydroxyl radicals) and other reactive species (e.g., hydrogen peroxide, peroxynitrite, and hypochlorous acid) are produced in the body, primarily as a result of aerobic metabolism. Antioxidants (e.g., glutathione, arginine, citrulline, taurine, creatine, selenium, zinc, vitamin E, vitamin C, vitamin A, and tea polyphenols) and antioxidant enzymes (e.g., superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidases) exert synergistic actions in scavenging free radicals. There has been growing evidence over the past three decades showing that malnutrition (e.g., dietary deficiencies of protein, selenium, and zinc) or excess of certain nutrients (e.g., iron and vitamin C) gives rise to the oxidation of biomolecules and cell injury. A large body of the literature supports the notion that dietary antioxidants are useful radioprotectors and play an important role in preventing many human diseases (e.g., cancer, atherosclerosis, stroke, rheumatoid arthritis, neurodegeneration, and diabetes). The knowledge of enzymatic and non-enzymatic oxidative defense mechanisms will serve as a guiding principle for establishing the most effective nutrition support to ensure the biological safety of manned space missions.
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PMID:Free radicals, antioxidants, and nutrition. 1236 82

Intracerebral infusion of lysed erythrocytes causes brain edema without inducing ischemic cerebral blood flow. Reports have indicated that oxidative damage contributes to secondary brain injury in stroke. In the present study, we investigated whether erythrocyte lysis after intracerebral hemorrhage (ICH) might result in oxidative brain damage. This study had four parts. Male Sprague-Dawley rats received an infusion of autologous lysed erythrocytes into the right striatum. Control rats only had a needle insertion. Neurological deficits, brain water and ion contents were determined in the first part. In the second part, hemoxygenase-1 (HO-1), manganese superoxide dismutase (Mn-SOD), copper/zinc SOD (CuZn-SOD) and protein carbonyl levels were determined by Western blot analysis. In the third part, immunohistochemistry was performed for HO-1. DNA damage was examined using DNA polymerase I-mediated biotin-dATP nick-translation (PANT) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) in the fourth part. Infusion of lysed RBCs induced marked edema in the ipsilateral striatum and profound neurological deficits. Western blot analysis and immunohistochemistry indicated that HO-1 was upregulated 24 h after infusion of lysed red blood cells. Both Mn-SOD and CuZn-SOD contents decreased, protein carbonyl levels increased in the ipsilateral striatum, and there was the appearance of PANT- and TUNEL-positive cells suggesting oxidative mechanisms in the erythrocyte-induced brain injury. In conclusion, oxidative stress caused by components of the lysed erythrocytes contributes to the brain injury after ICH.
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PMID:Oxidative brain injury from extravasated erythrocytes after intracerebral hemorrhage. 1238 37

Zinc ions seem to be important to several neurological functions and have been connected to the pathophysiology of epilepsy, neuronal cell death after seizure or stroke, and Alzheimer's disease. Both epilepsy and Alzheimer's disease are clinical conditions believed to involve the olfactory bulb. The mammalian olfactory bulb is densely innervated by zinc-enriched (ZEN) neurons, and the distribution of the ZEN terminals in the mouse olfactory bulb has previously been described. The aim of this study was to describe the origins of ZEN terminals projecting into the main olfactory bulb of the rat. Selective labeling of ZEN terminals was accomplished by intracerebral infusion of sodium selenide, whereby zinc selenium clusters are created in the ZEN terminals. Some of these clusters move by retrograde axonal transport to the somata where they can be silver-enhanced by autometallography (AMG). After infusion of sodium selenide into the main olfactory bulb, retrogradely labeled ZEN somata were found (1) ipsilaterally in all anterior olfactory nuclei, taenia tecta, piriform cortex and lateral entorhinal cortex, and (2) contralaterally in anterior olfactory nuclei except the external division. The ipsilateral anterior olfactory nucleus had the densest population of ZEN somata, and it was found that these somata originated mainly from pyramidal neurons in layers II and III of each area. The olfactory-related centrifugal afferents to the main olfactory bulb are discussed.
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PMID:Retrograde tracing of zinc-enriched (ZEN) neuronal somata projecting to the olfactory bulb. 1244 90

This article is dedicated to the mechanisms of ischaemic brain damage. The processes of glutamate-calcium cascade connected with formation of focal brain necrosis within the period of therapeutic window (the first 3-6 h after the induction of cerebral ischaemia) are discussed. The basis mechanisms of energy-dependent ionic pumps failure, development of glutamate excitotoxicity, disorders of calcium metabolism are analyzed. The results of own investigations are presented. The significant increases in the concentrations of excitatory aminoacidergic neurotransmitters (glutamate and aspartate) in the cerebrospinal fluid were demonstrated in patients with acute ischaemic strokes from the first hours of illness with no dependency on vascular origin of strokes. The extent and duration of these increases were of prognostic value for determining the severity and outcome of the stroke. It was showed that along with "excitotoxicity", the pathogenesis of ischaemic stroke also involves a deficiency of protective inhibitory GABAergic mechanisms and developing imbalance between the excitatory and inhibitory neurotransmitters systems. The significant increase of the level of the specific autoantibodies to phencyclidine-binding protein of glutamate NMDA-receptors was found out in blood serum of patients beginning from the first 3 h after stroke onset and it directly correlated with the severity of ischaemic stroke. The great attention is paid to the role of astroglia in energy metabolism and glutamate neurotransmission, to the mechanisms of regulation of concentrations of neurotransmitter amino acids in the synaptic cleft, as well as to the mechanisms of spreading depression waves and zinc neurotoxicity.
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PMID:[Glutamate neurotransmission and calcium metabolism in cerebral ischaemia and under normal conditions]. 1244 9

Compared with other regions in the United States, the southern region has had the highest stroke mortality rate and a more prevalent and resistant hypertension. We designed this analysis of the data obtained from the National Health and Nutritional Examination Survey III (NHANES-III), which is a community-based cross-sectional survey, to describe regional variations in blood pressure and the reported consumption of nutrients, focusing on those linked to blood pressure, in the United States. We selected the following variables from the NHANES-III data for this analysis: systolic and diastolic blood pressures, protein, carbohydrates, total fatty acids, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, cholesterol, fiber, sodium, potassium, calcium, magnesium, zinc, copper, iron, riboflavin, niacin, thiamin, alcohol and vitamins C, E, B-6 and B-12. Of the 17,752 participants in the survey who were 18 y of age or older, the south had the highest systolic and diastolic blood pressures (P < 0.005 for each) and reported the highest consumption of monounsaturated fatty acids, polyunsaturated fatty acids and cholesterol (P < 0.05 for all) and the least amount of fiber in the multivariate analysis (P < 0.005). The highest reported sodium consumption was in the south region (3.4 +/- 0.02 g), and the lowest was in the west (3.2 +/- 0.03 g; P < 0.05). The south also consumed the least potassium, calcium, phosphorous, magnesium, copper, riboflavin, niacin, iron and vitamins A, C and B-6 (P < 0.005). There was no difference among the four regions in frequency of "adding salt on the table." The region of the United States that includes the "stroke belt" has dietary patterns that may contribute to the high prevalence of hypertension and cardiovascular disease.
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PMID:Regional variations of blood pressure in the United States are associated with regional variations in dietary intakes: the NHANES-III data. 1251 92


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