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

The effect of bicuculline-induced seizures on Na+,K+-ATPase activity of mouse cerebral cortex homogenates, using two different procedures of sample preparation (freezing in situ or decapitation of animals without freezing) is described. Regardless of tissue treatment Na+,K+-ATPase activities during bicuculline-induced seizures did not differ significantly from the appropriate controls when vanadate-free ATP was used as substrate. The response of Na+,K+-ATPase to K+ activation was also similar; the increase in potassium concentration from 2 to 20 mM caused a 33.0 and 32.3% increase of enzyme activity in cortical homogenates from control and convulsing mice, respectively. Vanadate added to the assay medium inhibited Na+,K+-ATPase activity in a dose-dependent manner; with both types of tissue treatment there was, however, a tendency towards lesser inhibition of the enzyme from convulsing mice and at 1 X 10(-7) M vanadate this difference, though slight, was statistically significant: -22.59 vs -27.55% (freezing) and -28.73 vs -38.42% (decapitation) for seizures vs controls, respectively. The reduced sensitivity of Na+,K+-ATPase towards vanadate inhibition in cortical homogenates prepared from mice with convulsions suggests that vanadate might play a role in the modulation of enzyme activity during seizures in vivo.
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PMID:The effect of vanadate on Na+,K+-ATPase activity of mouse cerebral cortex during bicuculline-induced seizures. 300 42

There has been increasing biochemical evidence since 1970 that one of the targets for convulsion-induced changes is the cell membrane of neurons. This is partly based on the observation that following seizures, there are increased levels of diacylglycerols and free fatty acids, which are products of the degradation of the major component of cell membranes, phospholipids. In addition, the production of prostaglandins from the free fatty acid, arachidonic acid, is activated after convulsions. This implies that alterations in the metabolism of lipids in brain are a major effect of seizures, and that the further study of these biochemical pathways may reveal important information pertinent to defining the basic mechanism of seizures and seizure-related pathology and may help in the development of potentially effective treatments. The effects of seizures on brain lipid metabolism and some recent studies from our laboratory are described in this chapter. Our results demonstrate that in rat brain, dexamethasone--a phospholipase A2 inhibitor--attenuates bicuculline-induced free fatty acid accumulation in a dose-dependent manner; bicuculline-induced status epilepticus does not alter the activation (synthesis of arachidonoyl coenzyme A) or acylation of fatty acids as assayed in vitro, indicating that the availability of high-energy cofactors (ATP) may be the critical factor responsible for decreased fatty acid acylation in vivo; bicuculline-induced fatty acid accumulation is localized mainly in the synaptosomal fraction of the rat brain; induction of seizures in the rat by bicuculline treatment produces a marked stimulation of lipoxygenase activity in synaptosomes that, in turn, results in a large increase in the synthesis of hydroxyeicosatetraenoic acids (HETEs). This effect is also observed following membrane depolarization with 45 mM K+, and bicuculline-induced status epilepticus stimulates the synthesis of prostaglandin D2. Possible mechanisms and consequences of alterations in specific lipids are described. Also, the possible involvement of a stimulated arachidonic acid cascade, particularly of hydroxylated products, in the release of neurotransmitters is discussed. Other aspects of the interaction between neurotransmission and the production of eicosanoids are reviewed. The metabolic pathways leading to the "lipid effect"--i.e., the production of free fatty acids, diacylglycerols, and arachidonic acid metabolites (eicosanoids)--are numerous and involve a wide variety of enzymes. The mechanism of this "lipid effect" may involve a seizure-induced overstimulation of normal lipid pathways that operate in neurotransmission.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The accumulation of free arachidonic acid, diacylglycerols, prostaglandins, and lipoxygenase reaction products in the brain during experimental epilepsy. 301 Jun 83

In ventilated rats, levels of phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), diacylglycerol (DAG), triacylglycerol (TAG), free fatty acids (FFA) and phosphatidic acid, as well as their fatty acid contents, were measured in forebrain tissue after 1, 20 and 60 min of seizures induced by bicuculline. Cerebral energy state was also measured. PI decreased progressively throughout 60 min of seizures, whereas the levels of PIP and PIP2 did not change. DAG increased modestly and persistently. FFA increased markedly during the early seizure period, but decreased later. Following an initial drop, TAG rose above control. Phosphatidic acid did not change. The levels of ATP and energy charge potential decreased slightly and lactate accumulated. Stearic acid (18:0) and arachidonic acid (20:4) primarily accounted for the changes in the levels of the lipids. At the onset of seizures, the decrease of 18.0 and 20:4 in PI occurred in parallel with an enrichment of these fatty acids in FFA and DAG. Despite the fact that the losses of 18:0 and 20:4 from PI were quantitatively similar to each other at all times examined, the increase in free 18:0 was much larger than the increase in free 20:4 at 20 min of seizures. Concurrently there was a rise of 20:4 in TAG. As the FFA levels declined thereafter, 20:4 and docosahexaenoate (22:6) in TAG continued to increase. The results are consistent with the view that seizure activity stimulates the hydrolytic breakdown of brain phosphoinositides--the pathway catalyzed by phosphodiesterase of the phospholipase C type followed by lipases, and probably the pathway catabolized by phospholipases A as well. Preferential incorporation of polyunsaturated fatty acids into TAG-acyl residues may represent a mechanism to reduce the level of their free forms when the latter are produced in large amounts.
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PMID:Cerebral phosphoinositide, triacylglycerol and energy metabolism during sustained seizures induced by bicuculline. 303 62

An infant with the acute neonatal form of pyruvate carboxylase deficiency (cross-reacting material negative) presented with severe intractable lactic acidosis within 4 h after birth. He also had hyperammonemia, hypercitrullinemia, and hyperlysinemia. Plasma glutamine was not elevated. He had a rapidly deteriorating clinical course with severe liver dysfunction, repeated septicemia and seizures; he was comatose and was on a ventilator throughout; death occurred at 8 wk of age. Skin fibroblast study confirmed the enzyme deficiency. Detailed biochemical parameters and histopathology of the brain and liver are presented. The evidence from this infant suggests that disturbances of intracellular oxaloacetate levels as a result of the primary enzyme defect might also contribute to deficiency in ATP generation which may explain the various other biochemical changes and liver pathology.
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PMID:Biochemical and histologic pathology in an infant with cross-reacting material (negative) pyruvate carboxylase deficiency. 308 60

The cerebral metabolic response to bicuculline (BC)-induced status epilepticus (SE) was studied in two-week-old ketamine-anesthetized marmoset monkeys. During 30-min clonic seizures, mean blood pressure, plasma glucose and paO2 did not decrease and plasma lactate doubled. Brains were funnel-frozen and punch biopsies of frontoparietal cortex, temporal cortex and thalamus were analyzed for ATP, phosphocreatine (PCr), glucose and lactate. There were marked reductions of ATP (to 56-77% of controls), PCr (to 23-28% of controls) and glucose (to 1-4% of controls), and lactate increased 3- to 6-fold in seizure animals. NADH fluorescence increased during seizures in cerebral cortex, thalamus, amygdaloid nuclei, hippocampus, posterior striatum and hemispheric white matter. This suggests a reduced tissue redox state in these regions and is correlated with the high energy phosphate depletion and elevated lactate in cortex and thalamus. Our results demonstrate a significant depletion of energy reserves and glucose in cerebral cortex and thalamus during neonatal seizures in the absence of adverse systemic factors. These seizure-induced metabolic changes in brain could have adverse long-term effects on brain development and function.
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PMID:Generalized seizures deplete brain energy reserves in normoxemic newborn monkeys. 313 58

A new NMR technique for nondestructive, noninvasive, nonradioactive concurrent measurements of blood flow and several energy-dependent metabolites were applied to in situ cat brain during high cerebral blood flow states (seizures) and low flow states (carotid occlusion plus hemorrhagic shock). An inductively coupled, quadruple-tuned surface coil with a 50-ohm match at all relevant frequencies was used for both excitation and receiving. A broadband spectometer was used to measure the 31P spectrum (PCr, ATP, Pi, and pH), a water-suppressed 1H spectrum (lactate), 23Na, and 19F (blood flow via CHF3 washout). Each nucleus was excited at an independently determined rate. Sodium, with a short T1, was excited more frequently than phosphorus. The results qualitatively agreed with other techniques. Blood flow greatly increased during seizures with a 10% decrease in the Na signal, minimal lactate accumulation, no pH shift, and a change in the PCr-to-Pi ratio from 3.4 to 1.7. During carotid occlusion plus hypotension blood flow, PCr and ATP decreased to less than 10% of baseline values. Changes in PCr and Pi preceded parallel changes in Na and ATP. These experiments demonstrated the feasibility of concurrent measurements of physiologically induced changes in high-energy phosphates, lactate, sodium, and blood flow from the same volume of brain, in a nondestructive manner using NMR spectroscopy.
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PMID:Concurrent measurements of cerebral blood flow, sodium, lactate, and high-energy phosphate metabolism using 19F, 23Na, 1H, and 31P nuclear magnetic resonance spectroscopy. 317 56

Glycerol, the end product of phospholipid degradation, was measured in cat brains under pathophysiological conditions known to cause activation of lipolysis, namely, bicuculline-induced seizures, permanent focal cerebral ischemia (2 hr of middle cerebral artery occlusion), and global cerebral ischemia (15 min of complete cerebral ischemia with or without 2 hr of recirculation). In addition, ATP and lactate were measured in order to correlate the activation of lipid degradation with disturbances in the energy-producing metabolism. A highly significant increase in the tissue glycerol content was observed after 1 hr of bicuculline-induced seizures (from 0.29 +/- 0.07 mumol/g in control animals to 1.30 +/- 0.06 mumol/g in seizure animals; P less than 0.001) or after 15 min of complete cerebral ischemia (from 0.29 +/- 0.07 to 1.17 +/- 0.14 mumol/g; P less than 0.01). Furthermore, a close correlation was found between the increase in glycerol and the increase in lactate or decrease in ATP after permanent focal ischemia. In contrast, following recirculation after complete cerebral ischemia, restoration of the energy pool did not lead to a reduction of the glycerol formed during ischemia. It is concluded that glycerol is a useful indicator of lipid degradation under pathological conditions. Since glycerol formed during vascular occlusion is trapped in brain cells, presumably owing to low glycerol kinase activity, it can be used as a stable postischemic indicator of ischemia-induced lipid degradation.
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PMID:Glycerol as an indicator of lipid degradation in bicuculline-induced seizures and experimental cerebral ischemia. 350 34

Rats treated intravenously with an organophosphorus anticholinesterase compound, paraoxon or soman, were sacrificed 2 to 131 min later, using 0.7 sec of focused microwave irradiation (25 kW at 915 MHz). Brain regional rates of glucose utilization during 3-min intervals were determined with labeled glucose and fluorodeoxyglucose as tracers. Levels of glucose, lactate, ATP, and creatine phosphate were assayed in the same samples. The two compounds differed markedly in their effects on brain metabolism. Paraoxon (0.8 LD50) depressed rates of glucose use in all brain regions, without causing consistent changes in brain metabolite levels. This depressant effect was most pronounced during the first 30 min after toxin exposure and had largely disappeared by 2 hr. Soman (0.8-0.95 LD50) was variable in its effects. Animals that showed seizure-like behavior had marked increases in glucose use in diencephalon and cerebrum but no changes in cerebellum or brain stem. Rapid rates of glucose use were associated with high levels of lactic acid and lower levels of creatine phosphate. In cerebrum, but not diencephalon, levels of ATP fell by as much as 50% in strongly affected animals by 30-130 min after soman. All of these effects were reversible with atropine. Soman-treated animals that did not have seizure-like activity did not exhibit these brain metabolic changes. These results and those of others show that cholinergic compounds vary greatly in their effects on brain glucose and energy metabolism. Although noncholinergic mechanisms are a possibility, the most parsimonious explanation for these findings is that cholinesterase inhibitors vary in their affinity for different central nervous system (CNS) acetylcholine receptor populations.
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PMID:Cerebral metabolic effects of organophosphorus anticholinesterase compounds. 350 39

In order to assess the early regional changes in energy metabolism in bicuculline induced seizures, mice were injected and sacrificed before the onset of overt seizure activity, and shortly after clonic-tonic seizures began. The energy metabolites glucose, ATP, and phosphocreatine were measured in layers of the motor cortex and the cerebellar vermis. Results showed minimal metabolite changes in the cerebellum, whereas changes in energy metabolism in the motor cortex were largely localized to the layers containing pyramidal cells. These results are in agreement with previous studies showing a relative sparing of the cerebellum, and suggest early cortical changes occur in pyramidal cells.
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PMID:Regional cerebral energy metabolism in bicuculline induced seizures. 358 95

The effect of electroconvulsive shock on the labeling of phospholipids and neutral lipids in mice brains was examined after intracerebral injection of [1-14C] arachidonic acid or [1-14C]palmitic acid. Electroconvulsive shock reduced greatly the removal of radiolabeled arachidonic acid from the free fatty acid pool. At the same time, the incorporation of arachidonic acid was partially inhibited in triacylglycerol, diacylglycerol, and phosphatidylinositol, whereas the incorporation of [1-14C]palmitic acid was not affected. Pretreatment with desipramine and pargyline potentiated the lipid effect of electroconvulsive shock in neutral glycerides. These electroconvulsive shock-induced changes reflect alterations in the metabolism of intracerebrally injected arachidonic acid, but not of similarly injected palmitic acid. From the available data whether decreased ATP, enzyme inhibition or other factors are involved cannot be ascertained. Moreover, the electroconvulsive shock-enhanced endogenous free arachidonic acid may possibly dilute the injected radiolabeled fatty acid, thus decreasing its availability for arachidonoyl-coenzyme A synthesis. Hence, a partial inhibition of the activation-acylation of these fatty acids, primarily arachidonic acid, also may be involved in the seizure-induced accumulation of free fatty acids in the brain.
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PMID:Reduced labeling of brain phosphatidylinositol, triacylglycerols, and diacylglycerols by [1-14C]arachidonic acid after electroconvulsive shock: potentiation of the effect by adrenergic drugs and comparison with palmitic acid labeling. 370 2


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