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

Reduce nicotinamide adenine dinucleotide (NADH) fluorescence was recorded from an avascular area on the squirrel monkey cortex prior to, during, and after focal incomplete ischemia. By using the instrumentation described, stable recordings were obtained free from hemoglobin artifact and with only minimal photodecomposition. Pentobarital was compared to urethane and halothane as the anesthetic agent and was found acceptable for these types of studies in the dosages used. NADH levels were constant prior to ischemia, increased during ischemia, returned to pre-ischemic levels after restoration of blood flow, and then increased greatly at death produced by anoxia. The use of the infrared microscope for semiquantitative measurements of cortical blood flow throughout the duration of these acute studies was investigated and found to the reliable.
Stroke
PMID:Reduced nicotinamide adenine dinucleotide fluorescence and cortical blood flow in ischemic and nonischemic squirrel monkey cortex. 1. animal preparation, instrumentation, and validity of model. 16 72

The fluorescence of reduced nicotinamide adenine dinucleotide (NADH) from cerebral cortex was measured before, during, and after middle cerebral artery (MCA) occlusion and then at death of the animal. In normal cortex, NADH remained constant throughout a wide range of variations in blood pressure and Paco2. In ischemic cortex, NADH levels were higher in hypovolemic hypotensive animals than in normotensive normovolemic animals. Neither hypercapnia nor hypocapnia was effective in decreasing NADH in regions of ischemia, but the latter was associated with a degree of hypotension that interfered with interpretation of data. NADH returned to normal with restoration of flow, supporting the reversibility of this degree of ischemia. The high levels of NADH at death, compared to those during ischemia, are consistent with incomplete ischemia in this model of cerebral infarction.
Stroke
PMID:Reduced nicotinamide adenine dinucleotide fluorescence and cortical blood flow in ischemic and nonischemic squirrel monkey cortex. 2. effects of alterations in arterial carbon dioxide tension, blood pressure, and blood volume. 16 73

Two infants who had clinical and radiographic findings consistent with Leigh syndrome were found to have deficiency of complex I (reduced nicotinamide-adenine dinucleotide--coenzyme Q reductase) activity. Significant abnormalities were found on computed tomographic scans and magnetic resonance images of the brain. Lactate and pyruvate concentrations in blood and cerebrospinal fluid were elevated, and muscle biopsy specimens showed abnormal mitochondria. These data indicate that Leigh syndrome, as well as MELAS syndrome (mitochondrial encephalopathy, myopathy, lactic acidosis, and stroke-like episodes) may result from complex I deficiency.
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PMID:Complex I (reduced nicotinamide-adenine dinucleotide-coenzyme Q reductase) deficiency in two patients with probable Leigh syndrome. 210 30

To clarify the mechanism of its effect on ischemic stroke, we investigated the effect of nimodipine, a dihydropyridine calcium antagonist, on changes in cytosolic free calcium, cortical blood flow, and histologic changes following focal cerebral ischemia and reperfusion in 14 cats. Using indo-1, a fluorescent intracellular Ca2+ indicator, we simultaneously measured changes in the Ca2+ signal ratio (400:506 nm), reduced nicotinamide adenine dinucleotide fluorescence (464 nm), and reflectance (340 nm) during an ultraviolet excitation (340 nm) directly from the cat cortex in vivo. In six cats treated with vehicle only, the calcium signal ratio increased from 5 minutes after middle cerebral artery occlusion to 30 minutes into reperfusion. The elevation of cytosolic free calcium was significantly attenuated by nimodipine, which was administered by intravenous infusion in eight cats starting 5 minutes after occlusion. Nimodipine had no effect on cortical blood flow during ischemia but induced a hyperperfused state following reperfusion. Nimodipine did not modify changes in the mitochondrial oxidation-reduction state. Nimodipine proved to have beneficial effects on recovery of the electroencephalogram following reperfusion as well as on the extent of focal histologic damage. Our results suggest that nimodipine, when administered during the early stage of focal ischemia, can favorably modify the outcome of stroke by reducing the Ca2+ entry during both the ischemic and reperfusion periods.
Stroke 1989 Nov
PMID:Nimodipine attenuates both increase in cytosolic free calcium and histologic damage following focal cerebral ischemia and reperfusion in cats. 281 88

An increase in cytosolic free calcium concentration ([Ca2+]i) may trigger irreversible cell injury following cerebral ischemia. We have measured changes in [Ca2+]i in cat cortex in vivo during ischemia produced by 1 hour of middle cerebral artery occlusion and during 30 minutes of reperfusion. Indo-1, a fluorescent Ca2+ indicator, was loaded into the exposed cortex by superfusion, and changes in the [Ca2+]i signal (400/506 nm ratio) were measured microfluorometrically during ultraviolet excitation (340 nm). The nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD/NADH) redox state and hemodynamic changes were measured simultaneously. The animals showing severe deterioration in their electroencephalograms (EEG) showed a progressive increase in the [Ca2+]i signal during ischemia (baseline: 1.46 +/- 0.05; 60 minutes after occlusion: 2.99 +/- 0.37; n = 7). At 30 minutes following reperfusion, the animals showing little recovery in their EEG exhibited a further increase in [Ca2+]i (4.71 +/- 0.87, n = 3), whereas animals showing significant recovery in their EEG also showed recovery of [Ca2+]i (1.55 +/- 0.09, n = 4). By contrast, the moderate or mild stroke animals with less deterioration in their EEGs showed no increase in [Ca2+]i during either ischemia or reperfusion. These data suggest that the increase in [Ca2+]i might be closely related not only to deterioration of brain function during ischemia but also to poor recovery during the reperfusion period.
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PMID:In vivo measurement of cytosolic free calcium during cerebral ischemia and reperfusion. 314 14

The effect of arterial hypotension on cerebral cortical tissue levels of adenosine triphosphate (ATP), phosphocreatine (PGr), lactate, and reduced nicotinamide adenine dinucleotide (NADH) was studied in male Wistar rats with unilateral carotid ligation exposed to arterial by hypoxia (PaO2 25 torr) for 20 min. while the body temperature was maintained at 32 degrees C and 27 degrees C. Brain metabolite levels were normal in normotensive hypothermic animals exposed to hypoxia, but reduction in arterial pressure to 75 torr caused a significant (p less than 0.05) decrease in ATP and PCr values and a significant increase in lactate and NADH levels. These changes were comparable to those of normothermic normotensive, hypoxic animals. Furthermore, there was no significant differences in the brain metabolite levels between the two hypotensive hypoxic groups. These results indicate that arterial hypotension severely alters the cerebral protective effect of hypothermia against injury caused by hypoxia, and that further reduction in body temperature (from 32 degrees C to 27 degrees C) will not prevent the harmful effect of hypoxia upon the brain in hypotensive rats.
Stroke
PMID:Reduction of the cerebral protective effect of hypothermia by oligemic hypotension during hypoxia in the rat. 680 24

A previous study has shown that endogenous adenosine trapping during ischemia (by blocking adenine nucleoside transport and inhibiting adenosine breakdown) prevents myocardial stunning. In this study, we tested the hypothesis that delay of administration of inhibitors until reperfusion would similarly prevent myocardial stunning in the absence of entrapped adenosine. In both studies, a selective nucleoside transport blocker, p-nitrobenzyl-thioinosine, was used in combination with a potent adenosine deaminase inhibitor, erythro-9-(2-hydroxy-3-nonyl)adenine, to entrap adenosine (preischemic treatment) or inosine (postischemic treatment) in an in vivo canine model of reversible global ischemia. Twenty-five anesthetized adult dogs were instrumented (by sonomicrometry) to monitor left ventricular performance from the relationship between stroke work and end-diastolic length as a sensitive and load-independent index of contractility. Hearts of animals supported by cardiopulmonary bypass were subjected to 30 minutes of normothermic global ischemia and 60 minutes of reperfusion. Saline solution containing the pharmacologic agents were infused into the bypass circuit before ischemia (group 1) or during reperfusion (group 2). Control group (group 3) received saline before and after ischemia. Myocardial biopsy specimens were obtained before, during, and after ischemia, and levels of adenine nucleotides, nucleosides, oxypurines, and the oxidized form of nicotinamide-adenine dinucleotide were determined. Left ventricular contractility fully recovered within 30 minutes of reperfusion in the groups treated with erythro-9-(2-hydroxy-3-nonyl)adenine and p-nitrobenzyl-thioinosine (p < 0.05 versus control group). Myocardial adenosine triphosphate was depleted by 50% in all groups at the end of ischemia. Adenosine triphosphate recovered during reperfusion only in the group that was treated with inhibitors before ischemia (group 1). At the end of ischemia, adenosine levels were low (< 10% of total nucleosides) in the control group (group 3) and in the group treated only after ischemia (group 2). A high level of adenosine (> 90% of total nucleosides) was present in group 1. We infer that selective pharmacologic blockade of nucleoside transport, only after ischemic injury, accelerated functional recovery during reperfusion, even without trapping of endogenous adenosine during ischemia and without adenosine triphosphate recovery during reperfusion. Recovery of myocardial adenosine triphosphate required preischemic treatment and adenosine entrapment during ischemia and reperfusion. Therefore, nucleoside trapping may be used to prevent reperfusion-mediated injury after reversible ischemic injury.
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PMID:Nucleoside trapping during reperfusion prevents ventricular dysfunction, "stunning," in absence of adenosine. Possible separation between ischemic and reperfusion injury. 804 Nov 75

65 patients with ischaemic stroke were treated for 6 weeks by intramuscular injections of Sygen--monosialoganglioside 40 mg daily. The results were double-blinded and compared with those in placebo group (Vitamin PP). The results evaluated by Mathew scale did not show any significant differences between both groups. However in the Sygen group we have noticed more patients with very good therapeutic results (almost complete recovery of functions). Immunological studies have not revealed any reaction, which may be considered as a result of allergogenic action of monosialoganglioside.
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PMID:[Trials of monosialoganglioside (Sygen) treatment in ischemic stroke]. 850 57

Decreased activity of complex I (NAD:ubiquinone oxidoreductase) is the most frequent biochemical finding associated with mutation at the base pair 3243 of the mitochondrial DNA. The mutation has been previously shown to lead to a defective translation. We hypothesized that due to an imperfect assembly of complex I subunits the substrate affinity of this enzyme may be lowered and this may be counteracted by increasing the mitochondrial NAD+NADH concentration. Therefore, we studied the effect and mechanism of action of nicotinamide treatment in a MELAS patient with the base pair 3243 mutation. Nicotinamide treatment was initiated after his first stroke-like episode. The blood NAD concentration (representing the intracellular concentration in erythrocytes) increased linearly being 24-fold at 6 weeks of treatment. Blood lactate and pyruvate concentration decreased by 50% within three days and 24 h urine lactate content within 2 weeks and we observed a clinical improvement together with a decrease in the lesion volume in magnetic resonance imaging within the first month. The cellular NAD increase upon nicotinamide administration was probably universal, because it occurred in a time and dose-dependent manner in cultured fibroblasts from both the patient and the controls. Alleviation of the lactate accumulation during the nicotinamide treatment suggests that an increase in the cellular NAD+NADH concentration leads to enhancement of the oxidation of reducing equivalents. However, the Km of complex I for NADH in skeletal muscle from the patient was similar to that of controls. This may indicate that physiologically mitochondrial complex I operates at non-saturating substrate concentration, and this may explain the effect of nicotinamide treatment.
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PMID:Increase of blood NAD+ and attenuation of lactacidemia during nicotinamide treatment of a patient with the MELAS syndrome. 859 19

The purpose of this study was to assess the relationship between morphological and metabolic changes in brain edema using proton magnetic resonance systems. The serial changes during the first 24 hours in the cold-injury trauma rat brain model were investigated by proton magnetic resonance imaging (1H MRI) and high-resolution proton MR spectroscopy (1H MRS). We also analyzed the efficacy of AVS 1,2-bis (nicotinamide)-propane which can scavenge free radicals to the edema in this experiment. The edema was developing extensively via the corpus callosum in ipsi- and contralateral hemispheres as shown by gradually increased signal intensity on 1H MRI. 1H MRS initially showed accumulation of acetate and lactate, and transient increasing of glutamine. After 24 hours, the increased glutamine decreased below the control, alanine increased, and N-acetyl asparatate decreased with the edema development. AVS-treatment significantly suppressed edema development, increases of lactate and alanine and decreases of N-acetyl asparatate. We suggest that the cold-induced lesion contains anaerobic glycolysis deterioration and results in severe brain tissue breakdown. AVS is proved valuable for the treatment of this edema lesion. Clinical 1H MRS showed prolonged lactate elevation and significant decreases of other metabolites in human ischemic stroke edema. In peritumoral edema, decreased N-acetyl asparatate gradually improved, and slightly elevated lactate disappeared after tumor removal. 1H MRS feasibly characterizes the ischemic and peritumoral edema and makes a quantitative analysis in human brain metabolism. We believe the combined 1H MRI and MRS study is a practical method to monitor the brain conditions and will make it easy and possible to find new therapeutic agents to some brain disorders.
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PMID:[Sequential observations of brain edema with proton magnetic resonance imaging and spectroscopy]. 872 79


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