UMLS:C0036572 - FACTA Search

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

Total, Mg2+-, Na+,K+-, and Ca2+-ATPase activities were studied in fresh brain membrane preparations from adult epileptic (El) mice and nonepileptic C57BL/6J (B6) mice. The El mice have an inherited type of temporal lobe epilepsy. No significant differences were observed between the El and B6 mice for any of the ATPase activities in the hippocampus, brain stem, or cerebellum. These findings indicate that seizure susceptibility in El mice is not associated with differences in the activities of these cationic ATPases and that seizure susceptibility in El mice and audiogenic DBA/2 mice may involve different biochemical mechanisms.
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PMID:Brain cationic ATPase activities in epileptic (El) mice. 283 Jan 30

Hemorrhage within the central nervous system (CNS) may be associated with subsequent development of seizure states or paralysis. Prior investigations indicate that hemoglobin, released from extravasated erythrocytes, may be toxic to the CNS by promoting peroxidation of lipids and inhibition of Na,K-ATPase. These deleterious effects are blocked both in vitro and in vivo by the Fe3+ chelator, desferrioxamine, indicating the involvement of free iron derived from hemoglobin. We now report that the Fe2+ chelator, ferene, also inhibits methemoglobin- and ferric iron-mediated CNS lipid oxidation, reflecting the reduction of Fe3+ by some component of the CNS. This reduction is apparent in the accumulation of the highly chromophoric ferene: Fe2+ chelate after the addition of Fe3+ salts to supernatants of murine brain homogenates. Because large amounts of ascorbic acid occur in mammalian CNS, we suspected that this reducing substance might be responsible. Indeed, the peroxidative effects of hemoglobin and iron on murine brain are blocked by washing of CNS membranes or by preincubation of crude homogenates with ascorbate oxidase. Furthermore, the addition of ascorbate to washed CNS membranes fully restores hemoglobin/iron-driven peroxidation. We conclude that posthemorrhagic CNS dysfunction may stem from damaging redox reactions between hemoglobin iron, ascorbic acid, and oxidizable components of the nervous system.
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PMID:Hemoglobin-mediated oxidant damage to the central nervous system requires endogenous ascorbate. 284 56

(Na+, K+)-ATPase (E.C.3.6.1.3) was partially purified from the cerebral cortex of audiogenic DBA/2 mice, from the primary and secondary epileptogenic foci of cats with a freeze lesion and from normal and epileptic human cortices. No differences in the specific activities of the microsomal enzyme were observed between normal and epileptic cortex. The influence of K+ ions and phenytoin, a potent antiepileptic drug, was then studied on the phosphorylation level of (Na+, K+)-ATPase alpha(+) (neuronal) and alpha(-) (non-neuronal) catalytic subunits resolved by SDS-gel electrophoresis. In normal cortex, the apparent affinity of the non-neuronal enzyme to K+ ions was reduced compared to the affinity of the neuronal enzyme. Phenytoin decreased the phosphorylation level of (Na+, K+)-ATPase purified from non-epileptogenic cortex of control C57/BL mice, cats and human patients. In fact, the drug induced the dephosphorylation of the (Na+, K+)-ATPase catalytic subunits, mainly of its alpha(-), non-neuronal subtype. In the cortex of audiogenic DBA/2 mice, K+ ions induced the dephosphorylation of (Na+, K+)-ATPase, with the same affinity as in control C57/BL mice. The dephosphorylating influence of phenytoin was however much decreased. In the primary and secondary foci of lesioned cats, both K+ and phenytoin dephosphorylating influences were decreased. Those changes were especially valid for the alpha(-), non-neuronal subunit. In human epileptic cortex, the (Na+, K+)-ATPase catalytic subunit had a decreased affinity to K+, as well as it lost its sensitivity to phenytoin dephosphorylation. Those results confirm the existence of two molecular forms of (Na+, K+)-ATPase in animal and human brain cortex. Those two forms, the neuronal and the non-neuronal or glial (Na+, K+)-ATPases, differ at least by their K+ regulation and their phenytoin sensitivity. Phenytoin studies also suggest that the drug stimulates the cortical (Na+, K+)-ATPase, mainly its glial form, providing central nervous system with an enhanced ability to regulate extracellular K+. In epileptic cortex, (Na+, K+)-ATPase and especially its glial form is altered in its K+ regulation and phenytoin sensitivity. That deficiency of glial (Na+, K+)-ATPase in focal epileptogenic cortex could be responsible for ictal transformation and seizure spread (Acta neurol. belg., 1988, 88, 257-280).
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PMID:Brain cortical (Na+ K+)-ATPase in epilepsy. A biochemical study in animals and humans. 285 92

Studies of various parameters of amino acid and catecholamine metabolism in human cerebral cortex have provided a number of biochemical markers that appear to delineate areas of focal epileptic activity. These observations have been consolidated further by investigations of a number of experimental models of epilepsy in animals. In appraising this data, it is important to take into consideration whether the tissue samples were obtained during an actual seizure state or in an interictal period. It is also important when possible to assess the extent of astrogliosis and neuronal loss. Sites of spontaneously active epileptic spiking in the cerebral neocortex have a somewhat different amino acid profile when compared to gray matter obtained from surrounding nonspiking gyri several centimeters away. There is an elevation in glycine content, a relative diminution in taurine, and a trend towards lowered glutamic acid levels. However, the concentrations of the eight amino acids measured appear in both the foci and surround to still be within the general range for normal tissue. Measurements of key enzymes involved in the synthesis and regulation of neurotransmitters provide a complementary method of evaluating functional changes in epileptic brain as they are generally less labile than their substrates. There is a moderate increase in the activity of glutamic acid dehydrogenase, an enzyme that plays an important role in the synthesis of glutamic acid from glucose. In some patients a decrease in glutamic acid decarboxylase has also been reported: this enzyme forms gamma-aminobutyric acid (GABA) from glutamic acid and is thus important for inhibition in the central nervous system. Moreover, there is a striking increase in the activity of tyrosine hydroxylase, the rate-limiting enzyme responsible for catecholamine synthesis. The possibility of a focal abnormality in catecholamine metabolism is reinforced by the simultaneous finding of a relative decrease in the number of alpha-1 postsynaptic receptor sites. An important marker of energy metabolism in neural tissue, Na+,K+-ATPase activity, has also been found to be decreased in actively spiking human cerebral cortex. Data from experimental animal foci produced by topical application of convulsant agents show a consistent drop in glutamic acid tissue content. This can be matched to an efflux of glutamic acid from the cortical surface, which in turn is proportional to the electrographic activity of the spike focus. In addition, there is often also a decrease in taurine and GABA in such foci, as well as an increase in the levels of a number of neutral amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Amino acid and catecholamine markers of metabolic abnormalities in human focal epilepsy. 287 18

The generation of focal cortical epilepsy as observed in human partial complex seizures is presumably due to enhanced physiologic responses or paroxysmal depolarization shifts (PDSs). However, the molecular mechanism that underlies these phenomena remains unknown. It could be due to a genetically determined error in a structural or regulatory protein or to posttranslational events that modulate membrane excitability. Since neither neuronal PDSs or interictal EEG spikes are sufficient to produce clinical epilepsy, the clinical expression of epilepsy may need the breakdown of neuronal or glial mechanisms that limit the spread of seizures. Hence, biochemical membrane studies of neurons and glia are necessary to understand the expression of human and experimental epilepsy. This chapter will review the role of glia in controlling neuronal excitability and neuron-glia relationships in experimental and human epilepsy. Data exploring the hypothesis that glial control of extracellular K+ or (K+)o is deficient in focal epilepsy induced by cold lesions will be reviewed. The role of glial carbonic anhydrase (CA) and glial control of putative amino acid transmitters in audiogenic epilepsy will be discussed. In the cold lesion, (K+)o activation constants of synaptosomal (Na+,K+)-ATPase are significantly decreased in the actively firing chronic focus, suggesting that the apparent affinity of the synaptosomal enzyme for K+ was increased within epileptic tissue that was actively firing. Interestingly, while sustained focal paroxysms could raise synaptosomal (Na+,K+)-ATPase, glial (Na+,K+)-ATPase and its activation by (K+)o remained decreased during sustained paroxysms in both acute and chronic lesions. Moreover, while the decrease of the absolute level of glial enzyme activity was less evident 45 days after lesion production, the poor response of glial enzyme to (K+)o never reversed to "normal" values. Hence, these experiments provided new information that glial (Na+,K+)-ATPase responds to K+ in a different manner when compared to synaptic enzyme. Glial ATPase and its activation by (K+)o remain decreased in either actively discharging acute lesions or in the indolent chronic foci. This could mean a reduction in the ability of glial membranes to maintain (K+)o homeostasis. As already suggested by Dichter, the impairment in glial control of elevated (K+)o could be mainly responsible for the transition of interictal discharges to ictal episodes, within the primary and the secondary foci.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuron-glia relationships in human and experimental epilepsy: a biochemical point of view. 287 19

Audiogenic seizure (AGS)-susceptible DBA/2 (D2) mice have a significant reduction in brain Ca2+-ATPase activity compared to AGS-resistant C57BL/6 (B6) mice. This reduction is inherited together with AGS susceptibility in B6 X D2 recombinant inbred strains. The Ca2+-ATPase reduction occurs in microsomes and synaptosomes, but not in mitochondria. This enzyme activity is measured at a high Ca2+ concentration (2 mM) with no added Mg2+ or EGTA. We further studied this Ca2+-ATPase activity and a Mg2+-dependent (Ca2+ + Mg2+)-ATPase activity in synaptic plasma membranes (SPM) from the B6 and D2 strains. Using EGTA or CDTA to adjust free Ca2+ concentrations, we measured Ca2+-ATPase activities at Ca2+ concentrations from 0.8 microM to 436 microM. The Ca2+-ATPase activity is consistently lower in the D2 than in the B6 SPM over all Ca2+ concentrations. The basal Mg2+-ATPase activity measured at 2 mM MgCl2, is also lower in SPM of D2 than B6 mice. Calcium stimulates the basal Mg2+-ATPase activity to the same extent in the SPM of the B6 and the D2 mice. Maximum stimulation in both strains occurs at 150 microM added CaCl2 (buffered with 100 microM EGTA). Higher Ca2+ concentrations inhibit this ATPase activity similarly in both strains. The EGTA-EDTA washing of SPM significantly reduces by 50% of the (Ca2+ + Mg2+)-ATPase activities of both strains, whereas calmodulin treatment restored these activities. Neither of these treatments, however, has any noticeable effects on the Ca2+-ATPase activities of the strains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Calcium ATPase activities in synaptic plasma membranes of seizure-prone mice. 293 83

Regional differences in Na,K-ATPase activity, and development of Na,K-ATPase activity were examined in rabbit hippocampus using a histochemical marker of enzyme activity. Stratum lucidum of CA3/CA2, corresponding to the mossy fiber terminal field, showed high Na,K-ATPase activity compared to stratum radiatum of CA1. A significant increase in Na,K-ATPase activity was found between 8 and 15 days postnatal. Tissues with limited Na,K-ATPase activity (immature hippocampus, the mature CA1 region) appear particularly prone to seizure-like abnormalities, perhaps reflecting an inability to regulate extracellular potassium.
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PMID:Developmental and regional differences in the localization of Na,K-ATPase activity in the rabbit hippocampus. 299 29

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

The effect of the ganglioside GM1 on amplitude of the electroencephalogram, neurologic function, and histology has been studied in chronic middle cerebral artery occlusion in cats. Ischemia was produced by a 2-hour occlusion of the left middle cerebral artery and was followed by a 7-day observation period. GM1 was intravenously administered 30 minutes after occlusion and daily during the observation period. Using the reduction in the electroencephalogram amplitude to measure stroke severity, three cats with mild, three cats with moderate, and three cats with severe stroke were treated with 5 mg/kg GM1. Nine cats, three in each group, were treated with 30 mg/kg GM1, while nine cats, three in each group, received middle cerebral artery occlusion but no treatment. In all cats there was a precipitous fall in mean electroencephalogram amplitude during occlusion, followed by a secondary fall during the observation period. Treated cats showed better recovery of electroencephalogram amplitude during the first 4 hours of reperfusion and a smaller secondary fall than untreated cats. Treated cats, especially those treated with 5 mg/kg GM1, showed significant recovery of neurologic deficits compared with untreated cats. Histologic damage was less in treated cats than in untreated cats. Some cats treated with 30 mg/kg GM1 exhibited convulsions, whereas no untreated cat showed any seizure activity. Our findings suggest that gangliosides may improve the recovery of both neurologic deficits and morphologic damage in the central nervous system. These positive effects might be tentatively explained by stimulation of enzymatic activities such as Na+, K+-ATPase and adenyl cyclase.
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PMID:Effect of the ganglioside GM1 on neurologic function, electroencephalogram amplitude, and histology in chronic middle cerebral artery occlusion in cats. 340 Jan 1

Previous studies have demonstrated that electrically induced seizures in rat result in an increased brain intracellular sodium which can be decreased by treatment with sodium diphenylhydantoin (DPH). The correlation of cation transport with membrane-oriented sodium-potassium-adenosine triphosphatase (Na-K-ATPase) prompted an investigation of the effect of DPH upon ATPase enzyme activity.Rat cerebral cortical synaptosomes isolated in Ficoll gradients were employed as the source for Na-K-ATPase. With 50 mM Na, 10 mM K, 7.5 mM Mg, and 1.8 mM ATP, the specific activity of the preparation was 70 mumoles P(i) released/mg synaptosomal protein per 30 min. The ionic and substrate concentrations yielding one-half maximal velocity were 0.5 mM K, 5 mM Na, and 8.5 x 10(-5) M ATP, respectively. At 50 mM Na and 0.2 mM K, DPH produced an average of 92% stimulation of P(i) release above control. The ratio of Na:K rather than the absolute levels of the ions was critical in determining the effect of DPH. DPH produced significant stimulation of enzyme activity under conditions of a high Na:K ratio (25-50:1). At ratios of 5-10:1, DPH produced little or no effect, and at low Na:K ratios (less than 5:1), DPH was inhibitory. Under all ionic conditions examined, DPH produced no apparent change in enzyme affinity for ATP. Assuming the proposed association of Na-K-ATPase with cation transport in brain, the data suggest the possibility that DPH may control seizures by its stimulation of Na-K-ATPase activity.
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PMID:Effect of diphenylhydantoin on synaptosome sodium-potassium-ATPase. 423 89

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