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

Both generalized and focal seizures dissociate brain polyribosomes and severely inhibit brain protein synthesis. This effect is found in freely convulsing animals and in animals that have been paralyzed and oxygen-ventilated in order to prevent hypoxemia, cerebral hypoxia, and other systemic changes associated with convulsions. Recent autoradiographic studies have shown that generalized seizures can result in striking focal inhibition of brain protein synthesis in adult rats and newborn marmoset monkeys. Local cerebral glucose metabolism and local cerebral blood flow were also studied in newborn marmosets by autoradiography. Although flow and metabolism are closely matched in control marmosets, seizures result in large local increases in 2-deoxyglucose metabolism, with lesser or no increases in local cerebral blood flow resulting in a relative mismatch. Those regions in which protein synthesis was most severely inhibited were those in which the relative mismatch between blood flow and metabolism was most marked. The molecular mechanisms regulating protein biosynthesis are not known. Translational regulation during seizures appears to be exerted, in large part, at the initiation step. A likely mechanism is the inhibition of ternary complex formation, one of the early steps in the initiation process, by increases in the intracellular ratio of [GDP]:[GTP]. This ratio is related to the cells' energy charge. Reduced levels of ATP during seizures can lead to an increased ratio of [GDP]:[GTP] via of the enzyme nucleoside diphosphate kinase (E.C. 2.7.4.6) and to inhibition of protein synthesis initiation. Regulation of protein biosynthesis during seizures is likely to be complex and exerted at many sites; some of these possibilities are discussed.
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PMID:Brain protein metabolism in epilepsy. 242 96

Inbred DBA/2 (D2) mice have an inherited susceptibility to audiogenic seizures (AGS), whereas inbred C57BL/6 (B6) mice are resistant to these seizures. AGS susceptibility is genetically associated with a reduction of a brain Ca2+-ATPase activity. A novel apparatus was used for monitoring simultaneously the electrical activity and ATP release from brain slices. The amount of extracellular ATP detected in hippocampal slices following the electrical stimulation of Schaffer collaterals is significantly greater in D2 mice than in B6 mice. We suggest that the increased level of extracellular ATP in D2 mice is associated with reduced brain Ca2+-ATPase activity.
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PMID:Increased amount of extracellular ATP in stimulated hippocampal slices of seizure prone mice. 253 11

Hyper- but not normoglycemic cats exposed to 8 min of anoxia show neurologic signs (fasciculations, myoclonic jerks, seizures) that develop after a symptom-free period. We examined brain mitochondrial function and metabolite concentrations at 0, 1, 3, and 5 h following exposure to anoxia, to correlate biochemical findings with the presence ("symptomatic") or absence ("presymptomatic") of neurologic signs. Brain mitochondria isolated postexposure only from symptomatic cats showed markedly decreased (-50%), state 3 (ADP-stimulated), and uncoupler-stimulated respiration rates with NAD- and FAD-linked substrates. Respiratory control and ADP/oxygen (ADP/O) ratios remained unchanged, indicating, respectively, that coupling and efficiency of ATP synthesis were preserved. Thus, inhibition of electron transport chain function, not phosphorylative activity, may be rate limiting for respiration. During anoxia, hyperglycemic cats showed higher brain lactate levels (26 versus 20 mumol/g), but similar ATP and phosphocreatine concentrations, compared with normoglycemic cats. After exposure, in all animals lactate and phosphocreatine were restored to control levels, whereas ATP remained at 85%. Cats that became symptomatic demonstrated four- to sixfold increases in lactate and 50% reductions in phosphocreatine. At 3 and 5 h postexposure, symptomatic animals showed significant reductions in ATP concentrations. We conclude that although initially asymptomatic, hyperglycemic cats exposed to anoxia undergo a neurologic deterioration over several hours following reoxygenation that is correlated with inhibition of mitochondrial respiration, increases in tissue lactate, and decreases in energy state.
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PMID:Delayed neurologic deterioration following anoxia: brain mitochondrial and metabolic correlates. 256 72

Neuronal firing during experimental convulsions triggered a large increase in brain eicosanoid synthesis. Mature astrocytes are an important source of cerebral prostanoids. Endogenously formed prostaglandins possess anticonvulsive properties of biological relevance. These conclusions suggest new ideas that might explain the formation and functions of prostanoids in the brain. First, as augmented neuronal discharge is a prerequisite for enhanced prostanoid synthesis during seizures, a functional coupling between firing neurons and prostanoid-forming astrocytes may be expected. Second, the anticonvulsive effects of endogenous prostanoids suggest that astroglia-derived substances might regulate neuronal activity. The phenomenon of convulsion-induced prostanoid synthesis may, therefore, represent a new example of neuron-glia interaction. Neither K+-induced membrane depolarization nor receptor activation by drugs with affinity to alpha or beta adrenoceptors, dopamine, serotonin, muscarine, histamine, GABA, glutamate, aspartate, adenosine, and opioid receptors evoked eicosanoid synthesis in astrocytes. The only physiologically relevant ligand that induced prostanoid synthesis concentration dependently in astrocytes was ATP and related nucleotide triphosphates, as well as nucleotide disphosphates. In peripheral nerves ATP serves as a cotransmitter. The effect of the P2 agonists was reduced by pertussis toxin. The mechanism by which eicosanoids regulate neuronal activity remains to be elucidated.
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PMID:Formation and function of eicosanoids in the central nervous system. 267 46

Clinical studies using 31P and 1H MRS with a whole body 2.0 T MRI/MRS system are described. In most cases, techniques to quantitate absolute molar concentrations of metabolites in various organs were used. In the brain, AIDS, chronic stroke, and white matter lesions were associated with alterations of brain 31P metabolites. Epilepsy was associated with increased pH in the seizure focus. In the heart, dilated cardiomyopathy was associated with increased PDE/ATP while PCr/ATP was unchanged. In the liver, alcoholic hepatitis and cirrhosis were associated with diminished hepatic ATP while alcoholic hepatitis had increased pH and cirrhosis had decreased pH. This allowed differentiation of normal liver, alcoholic hepatitis, and alcoholic cirrhosis without biopsy. In the prostate, malignancy was associated with increased PME/ATP and decreased PCr/ATP. The PME/PCr was greatly increased in malignant prostate with no overlap in normals. Other cancers outside the brain had increased PME and effective treatment was often associated with diminished PME. 1H MRS of the brain was performed using ISIS and outer volume suppression pulses for volume localization. Excellent high resolution 1H water-suppressed spectra were obtained at echo times as short as 30 ms, showing well resolved peaks for lactate, N-acetylaspartate, glutamate, choline, creatinine, and inositol. 1H MRS demonstrated that the uptake of ethanol by the brain was slower than the rise of ethanol in blood. 31P spectroscopic imaging of the brain with resolution of 2.25 x 2.25 x 2.5 cm produced metabolic images and high resolution spectra from desired regions of interest.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical magnetic resonance spectroscopy of brain, heart, liver, kidney, and cancer. A quantitative approach. 270 9

Improvement of energy metabolism in ischemic cerebral tissue benefits the therapy of occlusive cerebrovascular disorders. In the present study, the effects of 6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (idebenone) on neurological signs, such as ischemic seizures, lactate and ATP contents of the cerebral cortex, and local cerebral blood flow, were assessed in stroke-prone spontaneously hypertensive rats (SHRSP) with experimentally induced cerebral ischemia. Experimental cerebral ischemia was caused by bilateral carotid artery occlusion (BCAO) in male SHRSP (8-10 weeks old). Pretreatment with idebenone (10-100 mg/kg, p.o.) for 3 or 10 days delayed the onset of ischemic seizure (acute stroke) and prolonged survival time in SHRSP roughly in a dose-dependent manner. When the compound (100 mg/kg, i.p.) was given once 30 min after BCAO, it exerted similar ameliorating effects on the neurological deficits. When idebenone (100 mg/kg for 3 days) was given orally, it did not significantly inhibit the decrease in regional cerebral blood flow induced by BCAO. However, the same treatment markedly inhibited increases in the lactate content and lactate/pyruvate ratio and the decrease in ATP content of the cerebral cortex. The compound did not affect cerebral blood flow in normal rats. These results suggest that idebenone ameliorates the neurological deficits related to cerebral ischemia, and that this effect is mediated by improving cerebral energy metabolism.
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PMID:Effects of idebenone on neurological deficits, local cerebral blood flow, and energy metabolism in rats with experimental cerebral ischemia. 276 37

In this study, the cerebral hemisphere content of calcium as well as selected parameters of oxidative metabolism and electrophysiological function were assessed in normoglycemic and hyperglycemic rats that were exposed to ischemia produced by electrocautery of the vertebral arteries and reversible occlusion of the carotid arteries. In hyperglycemic animals, 0.5 h of ischemia was associated with large accumulations of lactate (27 mmol/kg), whereas normoglycemic animals showed lesser lactate accumulation (17 mmol/kg). At this sampling time (0.5 h of ischemia), both groups of ischemic animals showed tissue calcium contents that were unchanged from preischemic control levels. In normoglycemic animals, release of the carotid clamps and recirculation for 1.5-24 h was associated with normalization of lactate, ATP and phosphocreatine, clinical behavior, and EEG. During this 24 h of recirculation, cerebral calcium levels showed no changes. Hyperglycemic ischemic animals recirculated for 1.5-24 h showed a persistent lactic acidosis, depressed ATP and phosphocreatine, gross EEG abnormalities, seizures, and a high mortality rate. Again, during this 24 h period, cerebral calcium content showed no changes from preischemic control or from the matched saline-treated group. These data suggest that significant accumulation of calcium in brain tissue is not an early event in ischemic-hyperglycemic brain damage, and thus does not provide support for a role of calcium in the production of this form of ischemic damage.
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PMID:Influence of lactate accumulation on calcium content of ischemic and postischemic brain. 277 33

Cats were subjected to a 3.5-atm fluid percussion impact administered to the cerebral cortex. Near-infrared spectrophotometry (NIRS) was used to measure the quantity of oxyhemoglobin and total hemoglobin in the illuminated tissue as well as the cytochrome a, a3 redox state. Corroborative data were obtained by freezing brains with liquid nitrogen and measuring cortical concentrations of ATP, creatine phosphate (CP), and lactate. Immediately postimpact there was a rise in mean arterial pressure with a 38% increase of highly oxygenated blood and a shift toward oxidation in the cytochrome a, a3 redox state. By 4 hours postimpact, cytochrome a, a3 was becoming progressively reduced despite the persistence of hyperemia. This was associated with a significant (p less than 0.01) decrease in ATP and CP concentration. Additional studies in which a 0.5-sec, 100-v electrical seizure was induced before and after fluid percussion demonstrated significant differences in seizure response, indicating a failure of autoregulation.
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PMID:Failure of autoregulation after closed head injury: an experimental model. 283 18

Status epilepticus was induced in paralyzed, ventilated rats using bicuculline and was maintained for 50 to 120 minutes. Cerebral cortex, hippocampus, and cerebellum were assayed for calmodulin kinase II activity in vitro using [gamma-32P]ATP and polyacrylamide gel electrophoresis. Seizures resulted in a 3.2 fold decrease in calmodulin kinase activity in crude synaptic membranes of cortex and in a 8.2 fold decrease in hippocampal membranes. Cytosolic calmodulin kinase activity was slightly increased in rats in status epilepticus but statistical significance was not reached. Status epilepticus did not affect calcium/calmodulin-dependent kinase activity in cerebellar membranes or cytosol. These data suggest that intense firing associated with continuous seizure activity decreases calmodulin kinase activity in cortical and hippocampal synaptic membranes, which may result in altered neuronal excitability.
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PMID:Decreased calmodulin kinase activity after status epilepticus. 283 95

The main objective of these studies was to determine whether adenosine inhibits choline kinase in rat striata, leading to a decreased incorporation of choline into phosphorylcholine, a mechanism that may mediate seizure-induced increases in the levels of free choline in brain. Incubation of particulate and soluble fractions of striatal synaptosomes with adenosine or its metabolically stable analogues significantly inhibited enzyme activity. The inhibition was noncompetitive versus choline and competitive versus MgATP. Inhibitor constants for adenosine, 2-chloroadenosine, and 2',5'-dideoxyadenosine at the MgATP site were 94, 49, and 207 microM, respectively; these values were less than the Michaelis constant for MgATP (340 microM). To determine whether adenosine altered the phosphorylation of choline in an intact preparation, synaptosomes were incubated with [3H]choline in the presence or absence of adenosine or its analogues and the amount of [3H]-phosphorylcholine formed from the [3H]choline taken up was measured. All compounds tested significantly reduced the synthesis of [3H]phosphorylcholine. Results suggest that following seizures or hypoxia, when levels of adenosine increase and the concentration of ATP decreases, inhibition of choline phosphorylation may be manifest, resulting in increased levels of free choline in brain.
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PMID:Adenosine inhibits choline kinase activity and decreases the phosphorylation of choline in striatal synaptosomes. 283 62


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