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

Glutamate mediated excitotoxicity is a major area of experimentation due to the potential for prevention of morbidity and brain damage associated with stroke and brain trauma. We have developed a simple rapid method to study excitotoxicity in primary cortical neuronal cultures using propidium iodide (PI) fluorescence read by a multiwell fluorescence scanner. Transient (25 min) or continuous N-methyl-D-aspartate (NMDA) treatment led to progressive neuronal death over 24 h that was blocked by 1 microM MK-801, 10 microM ifenprodil, and 200 mM ethanol. Results with PI fluorescence were identical to those found using the lactate dehydrogenase (LDH) release and trypan blue staining assays of excitotoxicity. This method provides a simple rapid means to test the effects of drugs during glutamate excitotoxicity and to do accurate time course experiments of delayed neuronal death.
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PMID:Use of a multiwell fluorescence scanner with propidium iodide to assess NMDA mediated excitotoxicity in rat cortical neuronal cultures. 912 86

1. To observe the effect of nitric oxide (NO) on the myocardium, the NO synthesis inhibitor NG-nitro-L-arginine (L-NNA) was administered to hypercholesterolaemic stroke-prone spontaneously hypertensive (SHRSP) rats. 2. Hypercholesterolaemic SHRSP were produced by feeding SHRSP a high fat and high cholesterol diet (HFC) for 2 weeks. The rats were then divided into three groups: (i) the N group, which were fed the HFC diet containing 0.023% L-NNA and 1% NaCl in their drinking water (n = 10); (ii) the NH group, which were fed the HFC diet containing 0.023% L-NNA and 1% NaCl in their drinking water which also contained 80 mg/L hydralazine (n = 10); and (iii) the C group, which were fed the HFC diet and 1% NaCl in their drinking water (n = 10). 3. All rats in the N and NH groups died within 35 days of the initiation of L-NNA administration. Rats in the N and NH groups had significantly increased serum creatine phosphokinase, lactate dehydrogenase, glutamic oxaloacetic transaminase and serum total cholesterol levels compared with rats in the C group. 4. Fibrosis in response to necrosis was histopathologically observed in the hearts of all rats in the N and NH groups without exception. Occlusion or intimal thickening in the arteries adjacent to the necrotic regions was also observed. 5. These results suggest that nitric oxide deficiency induces myocardial infarction in hypercholesterolaemic SHRSP. These NO-deficient hypercholesterolaemic SHRSP offer a new model of myocardial infarction in rats.
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PMID:Nitric oxide deficiency induces myocardial infarction in hypercholesterolaemic stroke-prone spontaneously hypertensive rats. 914 85

We evaluated postoperative myocardial enzymes and function associated with cryoablation in 20 patients with Wolff-Parkinson-White syndrome undergoing surgical treatment for a single left-sided accessory conduction pathway. Ten patients underwent endocardial atrial incision with cryoablation using CO2 at -60 degrees C for 120 sec (group A), while the remaining 10 patients did not receive cryoablation (group B). Levels of aspartate aminotransferase (GOT), lactate dehydrogenase (LDH), and creatine kinase (CK-MB) on postoperative days 1, 2, and 3 were higher in patients in group A than in group B (p < 0.05). However, mean values remained low (GOT, 120.5 IU/L; LDH, 1105.1 IU/L; CK-MB, 76.3 IU/L). No electrocardiographic changes were detected. Parameters of cardiac function, including cardiac index, stroke volume index, systemic vascular resistance, and ejection fraction, remained unchanged during the postoperative period in both groups. Furthermore, 201Tl cardiac scintigraphy demonstrated no evidence of myocardial perfusion defects due to cryoablation in group A. In conclusion, myocardial damage induced by cryoablation is very minor and is not associated with any clinical impairment of cardiac function.
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PMID:Postoperative influences of surgical cryoablation for Wolff-Parkinson-White syndrome--a analysis of myocardial enzymes and function. 919 39

We measured serum creatine kinase (CK), lactate dehydrogenase (LD), aspartate aminotransferase (AST), and serum alanine aminotransferase (ALT) in 26 heat stroke (HS) victims and 10 control (non-heat-exhausted) subjects during annual Hajj in Makkah, Saudi Arabia. On admission to the HS treatment unit, serum CK, AST, ALT, and LD were higher in HS victims than controls (P < 0.05), and at 6, 12, and 24 h were higher than baseline concentration. The patient group was divided into three groups, (a) those who had a quick recovery, (b) those who were critically ill until the end of the Hajj period (7 days), and (c) those who died. Serum enzymes at the time of admission were significantly higher (P < 0.05) in the nonsurviving group (n = 6) and the severely ill (n = 9) than in those who had a quick recovery (n = 11). ROC curves were plotted for each enzyme. The most useful indicator was LD, as it could distinguish significantly between the groups who died and those who had a quick recovery (area under the curve = 0.991 +/- 0.0286). It was followed by CK and AST as useful prognostic factors. When compared with ROC curves for body temperature, anion gap, and serum potassium, the enzyme results were superior prognostic indicators.
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PMID:Serum enzymes in heat stroke: prognostic implication. 921 54

Administration of adenosine A1 receptor agonists in vivo is neuroprotective in various stroke models. Experiments using either mixed cultures of neurons and astrocytes or brain slices, in which several cell types are present, have demonstrated that activation of A1 receptors also id protective against hypoxia and/or hypoglycemia in vitro. In this study, we have examined the effect of the A1 agonist cyclopentyladenosine (CPA) on cellular damage, measured by efflux of lactate dehydrogenase (LDH), in highly enriched primary cultures of either neurons of astrocytes exposed to different metabolic insults. CPA reduced neuronal LDH release induced by a combination of hypoxia and substrate deprivation ("simulated ischemia"; IC50 = 28 nM) of by hypoxia alone (IC50 = 170 nM). In contrast, CPA had no effect on neuronal damage induced by substrate deprivation alone, not did it affect ischemic death to astrocytes. The neuroprotective effect of CPA during simulated ischemia and hypoxia were reversed by the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). These data demonstrate that activation of an adenosine A1 receptor on neurons, but not astrocytes, is protective against cellular damage of death induced specifically by hypoxia as opposed to other metabolic insults such as hypoglycemia.
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PMID:Adenosine A1 receptor activation preferentially protects cultured cerebellar neurons versus astrocytes against hypoxia-induced death. 937 19

Glutamate-mediated excitotoxicity is associated with adenosine triphosphate (ATP) degradation and generation of oxygen radicals. Hypoxanthine and lactate depict energetic impairment, while xanthine and uric acid reflect activity of radical producing xanthine oxidase. Cerebrospinal fluid (CSF) glutamate, hypoxanthine, lactate, xanthine, and uric acid were investigated in neurological patients. In multiple sclerosis, myelopathy, stroke, epilepsy and viral meningitis glutamate, hypoxanthine, xanthine, and uric acid are increased 2-3-fold compared to controls. Lactate is only elevated in meningitis. Normal lactate dehydrogenase (LDH) levels and absent correlation between the albumin ratio and neurochemical parameters exclude an artificial increase due to cell lysis and barrier damage. Absent correlation between neurochemical parameters within each patient group is most likely related to preserved glial and neuronal uptake mechanisms. CSF hypoxanthine, xanthine, and uric acid levels appear superior to lactate in reflecting glutamate-mediated excitotoxicity in neurological patients.
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PMID:Cerebrospinal fluid hypoxanthine, xanthine and uric acid levels may reflect glutamate-mediated excitotoxicity in different neurological diseases. 946 46

1. Incubation of bovine adrenal chromaffin cells with veratridine (10-100 microM) during 24 h, caused a concentration-dependent release of the cytosolic lactate dehydrogenase (LDH) into the bathing medium, an indicator of cell death. Lubeluzole or its R(-) enantiomer, R91154, did not enhance LDH release. Both lubeluzole and R91154 (0.3-10 microM) decreased the veratridine-induced LDH release. 2. Penfluridol did not increase LDH release at concentrations 0.003-1 microM; 3-10 microM increased LDH release to 50-60%, after 24 h exposure. Penfluridol (0.03-0.3 microM) did not protect against the cytotoxic effects of veratridine; at 1 microM, 15% protection was produced. Higher concentrations (3-10 microM) enhanced the cytotoxic effects of veratridine. 3. Ba2+ ions caused a concentration-dependent increase of LDH release. This cytotoxic effect was partially prevented by 3 microM lubeluzole and fully counteracted by 1 microM penfluridol. R91154 was less potent than lubeluzole and only protected against the lesion induced by 0.5 mM Ba2+. 4. Ouabain (10 microM during 24 h) increased LDH release to about 30%. Both lubeluzole (0.3-10 microM) and the lower concentrations of penfluridol (0.003-0.3 microM) prevented the ouabain cytotoxic effects. At higher concentrations (3 microM), penfluridol increased drastically the ouabain cytotoxic effects. 5. 6-Hydroxydopamine (6-OHDA) caused significant cytotoxic effects at 30 and 100 microM. Lubeluzole (3-10 microM) or penfluridol (0.03-0.3 microM) had no cytoprotective effects against 6-OHDA. 6. Lubeluzole (3 microM), R91154 (3 microM) and penfluridol (1 microM) blocked the current through Na+ channels in voltage-clamped chromaffin cells (I(Na)) by around 20-30%. Ca2+ current through Ca2+ channels (I(Ca)) was inhibited 57% by lubeluzole and R91154 and 50% by penfluridol. The effects of penfluridol were not washed out, but those of lubeluzole and R91154 were readily reversible. 7. Lubeluzole (3 microM) induced reversible blockade of the oscillations of the cytosolic Ca2+, [Ca2+]i, in fura-2-loaded cells exposed to 30 or 100 microM veratridine. Penfluridol (1 microM) inhibited those oscillations in an irreversible manner. 8. The results suggest that lubeluzole and its R-isomer caused cytoprotection against veratridine cell damage, by blocking the veratridine stimulated Na+ and Ca2+ entry, as well as the [Ca2+]i oscillations. The Ba2+ and ouabain cytotoxic effects were prevented more efficiently by penfluridol, likely by blocking the plasmalemmal Na+/Ca2+ exchanger. It remains dubious whether these findings are relevant to the reported neuroprotective action of lubeluzole in stroke; the doubt rests in the stereoselective protecting effects of lubeluzole in in vivo stroke models, as opposed to its lack of stereoselectivity in the in vitro model reported here.
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PMID:Effects of the neuroprotectant lubeluzole on the cytotoxic actions of veratridine, barium, ouabain and 6-hydroxydopamine in chromaffin cells. 972 Jul 90

Peroxynitrite triggers DNA single-strand breakage, which activates the nuclear enzyme poly(ADP-ribose) synthetase (PARS). Activation of PARS depletes its substrate, NAD+, slowing the rate of glycolysis, electron transport, and ATP formation, resulting in cell necrosis. Here, we demonstrate that inhibition of PARS with the novel, potent PARS inhibitor 5-iodo-6-amino-1,2-benzopyrone (INH2BP) protects against peroxynitrite-induced cell death (as measured by measurement of mitochondrial respiration and release of lactate dehydrogenase) in C6 glioma cells in vitro, and in a murine stroke model in vivo. Inhibition of PARS with INH2BP may represent a novel approach for the experimental therapy of stroke.
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PMID:Protective effects of 5-iodo-6-amino-1,2-benzopyrone, an inhibitor of poly(ADP-ribose) synthetase against peroxynitrite-induced glial damage and stroke development. 972 Oct 31

Ischemia-reperfusion injuries can occur with diseases such as myocardial infarction and stroke and during surgical procedures such as organ transplantation and correction of aortic aneurysms. We developed a murine model to mimic abdominal aortic aneurysm repair with cross-clamping of the aorta distal to the renal artery. After model development, we compared the normal complement BALB/c mouse with the C5-deficient DBA/2N mouse. To assess quantitative differences, we measured neuromuscular function up to 72 h after ischemia with a subjective clinical scoring system, as well as plasma chemistries, hematology, and histopathology. There were significant increases in clinical scores and creatine phosphokinase, lactate dehydrogenase, and muscle histopathology scores in BALB/c mice compared with those in DBA/2N mice and sham-surgery mice. Muscle histopathology scores of the cranial tibialis and quadriceps correlated well with clinical signs, creatine phosphokinase, and lactate dehydrogenase, and indicated the greatest pathology in these muscle groups. We developed a murine model of skeletal muscle ischemia-reperfusion injury that can utilize the benefits of murine genetic and transgenic models to assess therapeutic principles of this model. Additionally, we have shown a significant reduction in clinical signs, plasma muscle enzyme concentrations, and muscle pathology in the C5-deficient DBA/2N mouse in this model.
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PMID:A murine skeletal muscle ischemia-reperfusion injury model: differential pathology in BALB/c and DBA/2N mice. 980 69

The purpose of this study was to assess the possible relationship between maximal running speed, serum isoenzyme patterns of creatine kinase (CK) and lactate dehydrogenase (LDH) and echocardiographic indices of left ventricular function. A group of 15 healthy, 3-year-old Maremmano stallions were given a 100 day training programme. At the end of this the animals carried out a maximum speed test and were divided into 2 groups (A and B) according to whether or not they had attained a speed of 15 m/s. Venous blood samples were taken from each horse before exercise (T0), 2 min (T1) and 24 h (T2) after exercise. Total serum activity of CK and LDH was measured and their isoenzyme distribution pattern determined. The day before the speed test echocardiographic examination was carried out at rest to assess the left ventricular function by calculating telediastolic, telesystolic and stroke volume, ejection fraction and stroke index. Statistically significant differences were found for the CK isoenzyme pattern at T2, where Group A showed an increase in the MM fraction (P = 0.003) and a decrease in the MB fraction (P = 0.014). These changes were thought to be linked to an increased membrane leakage due to exercise and not to muscle fibre disruption because the CK and LDH total activities remained within the normal range. In Group A there was also greater left ventricular telediastolic volume (P = 0.044) and length (P = 0.033) at rest as well as a greater stroke index (P = 0.032). We concluded that the evaluation of CK pattern after exercise and of echocardiographic left ventricular function indices at rest made it possible to select for the fastest horses (Group A).
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PMID:Relationship between running speed, isoenzymes of serum creatine kinase and lactate dehydrogenase and left ventricular function in stallions. 1065 43


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