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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sustained, generalized seizure activity was induced in anaesthetized (70% N2O), paralyzed and artifically ventilated rats by i.p. DL-homocysteine thiolactone in a dose of 11 mmol/kg. Epileptic discharges in the EEG were accompanied by marked perturbation of tissue metabolites. There was a fall in phosphocreatine concentration to 40% of control but only moderate changes in adenine nucleotides, a marked rise in lactate concentration, and a pronounced increase in the lactate/pyruvate ratio. Excessive amounts of dihydroxyacetone phosphate (and glyceraldehyde phosphate) accumulated, indicating that depletion of NAD+ occurred. There was marked accumulation of ammonia, glutamine and alanine, and reduction in glutamate and aspartate concentrations. Administration of a subconvulsive dose of homocysteine (7.5 mmol/kg) gave rise to changes in ammonia and amino acids, qualitatively similar to those occurring during seizures. It is concluded that although changes in the metabolites of the energy reserve were mainly caused by the induced seizures, those affecting amino acid concentrations were significantly influenced by accumulation of ammonia, secondary to metabolism of injected homocysteine. Cerebral blood flow (CBF) and oxygen utilization (CMRO2) were measured during sustained seizures. CMRO2 rose to 150% of control, with a corresponding increase in CBF.
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PMID:Cerebral metabolic and circulatory changes in the rat during sustained seizures induced by DL-homocysteine. 50 26

A simple fluorescent spot screening test has been developed for the identification of individuals with arginase deficiency (hyperargininemia). The assay is based on the coversion of arginine to ornithine and urea by arginase present in 1/8 inch disc of dried blood on filter paper. The enzyme activity is visually estimated by the oxidation of NAD-H to NAD+ in a coupled kinetic reaction. In the absence of the enzyme, there is no oxidation of the NAD-H and consequently no loss of fluorescence. The screening assay has been used to identify successfully both heterozygous and homozygous arginase-deficient crabeater macaques (M. fascicularis) as well as three patients with hyperargininemia. This test can be used to screen large numbers of patients with mental retardation or seizure disorders rapidly to determine the frequency of this disorder more precisely.
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PMID:A simple screening test for arginase deficiency (hyperargininemia). 84 87

The effect of sodium cyanate (25, 50, 75, and 100 mg/kg body weight i.p. daily for 10 days) upon cerebral metabolism and the EEG of Wistar rats was studied. This treatment resulted in a dose-related carbamylation of hemoglobin and left shift in the oxygen dissociation curve. Animals receiving the highest dose of cyanate developed a significant systemic metabolic acidosis. In brain there was dose-dependent decrease in phosphocreatine, TCO2 and cytoplasmic NADH/NAD+ ratio, reflecting the calculated drop in intracellular pH. Glucose levels were elevated despite a normal calculated energy charge, which suggests a balanced slowing of the energy-producing and energy-utilizing systems. The higher doses of cyanate produced spontaneous seizure activity on the EEG.
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PMID:Effects of high-dose cyanate upon cerebral energy metabolism of the rat. 120 41

The objective of the present study was to assess metabolic changes in the neocortex and hippocampus of well-oxygenated or moderately hypoxic rats in which fluorothyl-induced seizures were sustained for 5 or 20 min, or which were allowed recovery periods of 5, 15, or 45 min following cessation of 20-min seizure activity by withdrawal of the convulsant gas. Sustained fluorothyl-induced seizures were found to cause metabolic alterations qualitatively and quantitatively similar to those previously observed with other commonly used convulsants. Thus, although the phosphorylation state of the adenine nucleotide pool remained only moderately perturbed, if at all, there were decreases in tissue concentrations of phosphocreatine and glycogen, and increases in those of cyclic AMP, lactate, and pyruvate, with a calculated fall in intracellular pH of about 0.15 units and a rise in the cytoplasmic NADH/NAD+ ratio. The enhanced metabolic rate was reflected in a marked reduction in the tissue-to-plasma glucose concentration ratio. Induced moderate hypoxia (arterial PO2 40-50 mm Hg) had no metabolic effect after 5 min of seizures but moderately increased lactate concentrations after 20 min (from about 10 to about 15 mumol X g-1). On cessation of seizure discharge cyclic AMP and phosphocreatine concentrations normalized already within 5 min, whereas glycogen and lactate concentrations normalized more slowly. In the neocortex (but not the hippocampus) postepileptic tissue-to-plasma glucose concentration ratios rose above control, probably reflecting metabolic depression. The results suggest that intracellular pH promptly returned to control, and that postepileptic alkalosis developed. They also suggest that some elevation of the NADH/NAD+ ratio persisted even after 45 min of recovery.
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PMID:Cerebral metabolic changes during and following fluorothyl-induced seizures in ventilated rats. 398 40

This study has investigated the feasibility of calculating the cytoplasmic free [NADP+]/[NADPH] ratio in rat brain. The time course of the change in the substrate ratios of the malate dehydrogenase (decarboxylating) [E.C. 1.1.1.40], NADP+-isocitrate dehydrogenase (decarboxylating) [E.C. 1.1.1.42] and 6-phosphogluconate dehydrogenase (decarboxylating) [E.C. 1.1.1.44] reactions was followed for up to 10 min after a single, unmodified electroconvulsive seizure. From the results it has been concluded that during periods of low flux, the direction and magnitude of the change in the cytoplasmic free [NADP+]/[NADPH] ratio can, in fact, be reasonably determined even though there is some uncertainty in the absolute value of the ratio itself. It is recommended that reliance not be placed on a single enzyme system but that one or both of the other systems also be observed under a given experimental condition to increase confidence in the determination. The results also demonstrate that seizure and anoxia have a far lesser effect on the cytoplasmic free [NADP+]/[NADPH] ratio than on the free [NAD+]/[NADH] ratio in the same compartment. These results suggest that the pathways using the nicotinamide-adenine dinucleotide phosphate system are relatively protected from the rapid fluctuations that seizure and anoxia can produce.
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PMID:The calculation of the cytoplasmic free [NADP+]/[NADPH] ratio in brain: effect of electroconvulsive seizure. 679 9

Experiments were done in vivo to determine the effect of oxygen at high pressure (OHP) on NAD+ and NADH in mouse brain cortex. A 7% decrease (N.S.) in NADH was found in brain cortex from mice exposed to 6 atm of 100% oxygen for 8 min, while a 20% decrease (P less than 0.01) in cortical NADH, when compared to controls, occurred when mice were exposed to this oxygen pressure for either 16 min or 48 min. A 20% decrease (P less than 0.05) in cortical NADH was also observed in mice which had been killed during hyperactivity (a state preceding convulsions), at seizure onset, or 10 s post-convulsions. No measurable change in cortical NAD+ was observed at any of these oxygen exposure times or stages of toxicity. When mice were exposed to either 3.5 atm or 6 atm of oxygen for 16 min, a statistically significant decrease in cortical NADH (P less than 0.01) coupled with an increase in the NAD+/NADH ratio was found only at 3.5 atm and 6 atm, and not at 1 atm. The decrease in cortical NADH and increase in the NAD+/NADH ratio were reversed when mice were decompressed and exposed to air for 30 min. Disulfiram, a drug found to delay the onset of oxygen seizures, did not prevent the oxygen-induced decrease in cerebral NADH or increase in the NAD+/NADH ratio. The decrease in cortical NADH in mice exposed to OHP did not correlate with the onset of oxygen-induced convulsions.
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PMID:NAD+ and NADH in brain cortex from mice exposed to high oxygen pressure. 692 50

This study is an investigation into the validity of calculating the mitochondrial redox state in brain in vivo using models of seizure and anoxia in rats. At six intervals following electroconvulsive seizure (0.5-10 min) and after 5 min of complete anoxia, multiple metabolites were measured in freeze-blown or freeze-clamped brain. From substrate ratios, the apparent changes in the mitochondrial free [NAD+]/[NADH] [H+] ratio were calculated from the L-glutamate dehydrogenase reaction [EC 1.4.1.3] and compared with shifts in the oxidized to reduced ratio of total ubiquinone (a component of the mitochondrial phosphorylation chain). During complete anoxia the calculated mitochondrial free [NAD+]/[NADH] [H+] ratio and the ubiquinone redox ratio both became more reduced by a factor of approximately 7. In contrast, following seizure the two indicators of the mitochondrial redox state moved in opposite directions. Mainly because of a large increase in tissue NH4+, the calculated mitochondrial free [NAD+]/[NADH] [H+] ratio paradoxically became more oxidized, plateauing between 2 and 10 min post seizure at a value approximately double that of the control. At the same time, however, the ubiquinone redox state fell to one-half the control value at two min and moved back towards normal between 5 and 10 min after the onset of the seizure. The results have been taken to be evidence against the applicability of the calculation of the mitochondrial free [NAD+]/[NADH] [H+] ratio from the L-glutamate dehydrogenase reaction in brain at least under conditions of rapid change. The results also suggest the possibility that the NH4+ produced during seizure is extra-mitochondrial and has relatively little tendency to diffuse into the matrix.
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PMID:The calculation of the mitochondrial free [NAD+]/[NADH][H+] ratio in brain: effect of electroconvulsive seizure. 709 92

Several processes by which astrocytes protect neurons during ischemia are now well established. However, less is known about how neurons themselves may influence these processes. Neurons release zinc (Zn2+) from presynaptic terminals during ischemia, seizure, head trauma, and hypoglycemia, and modulate postsynaptic neuronal function. Peak extracellular zinc may reach concentrations as high as 400 microM. Excessive levels of free, ionic zinc can initiate DNA damage and the subsequent activation of poly(ADP-ribose) polymerase 1 (PARP-1), which in turn lead to NAD+ and ATP depletion when DNA damage is extensive. In this study, cultured cortical astrocytes were used to explore the effects of zinc on astrocyte glutamate uptake, an energy-dependent process that is critical for neuron survival. Astrocytes incubated with 100 or 400 microM of zinc for 30 min showed significant decreases in ATP levels and glutamate uptake capacity. These changes were prevented by the PARP inhibitors benzamide or DPQ (3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone) or PARP-1 gene deletion (PARP-1 KO). These findings suggest that release of Zn2+ from neurons during brain insults could induce PARP-1 activation in astrocytes, leading to impaired glutamate uptake and exacerbation of neuronal injury.
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PMID:Zinc inhibits astrocyte glutamate uptake by activation of poly(ADP-ribose) polymerase-1. 1772 43