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

Adult C57BL/10Bg mice, normally resistant to audiogenic seizures, became susceptible when the mothers drank 10 per cent ethanol in water during pregnancy and for 14 days postpartem. Reserpine enhanced the incidence of seizures, and the effect was reversed by 5-hydroxytryptophan but not by dihydroxyphenylalanine. p-Chlorophenylalanine also enhanced the incidence of seizures, whereas alpha-methyl equals p equals tyrosine did not effect. Monsodium glutamate almost completely prevented seizures. These results are consistent with the interpretation that the serotonergic systems may be among those involved in the seizure mechanism induced by fetal and early exposure to ethanol.
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PMID:Effects of aminergic drugs and glutamic acid on audiogenic seizures induced by early exposure to ethanol. 12 3

The time course of changes in behaviour, seizure response and cerebral monoamine and gamma-aminobutyric acid (GABA) metabolism has been studied in relation to the anticonvulsant actions of di-n-propylacetic acid (DPA) and ethanolamine-O-sulphate (EOS) on sound-induced seizures in DBA/2 mice. Changes in cerebral monoamine metabolism after EOS (75 or 150 mug, intracerebroventricularly) were not related to its anticonvulsant action. The primary effect was GABA-transaminase inhibition (by 50-70%) leading to a 2-4 fold increase in cerebral GABA concentration. Increases in brain GABA concentration (maximally 36%), 5-hydroxyindoleacetic acid (5HIAA, maximally 134%) and homovanillic acid (HVA, maximally 183%) were seen after DPA (400-600 mg/kg, i.p.). The time course of the increases in HVA and 5HIAA did not correlate with the anticonvulsant effect. Elimination of these increases by the use of inhibitors of monoamine synthesis (alpha-methyl-p-tyrosine and p-chlorophenyl-alanine) did not alter the anticonvulsant effect of DPA. Experiments using probenecid suggested that the increases in 5HIAA and HVA after DPA result from inhibition of their active transport out of the brain.
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PMID:Monoamine and GABA metabolism and the anticonvulsant action of di-n-propylacetate and ethanolamine-O-sulphate. 13 17

Congenital carbamyl phosphate synthetase deficiency was diagnosed by liver biopsy in a 13-year-old girl, alpha-Keto analogues of essential amino acids have been shown to spare nitrogen by reducing urea formation; hence, they were given to this patient in the hope of reducing hyperammonemia and improving protein tolerance. After intravenous infusion of the keto analogues of valine, leucine, isoleucine, methionine and phenylalanine, the corresponding plasma amino acids, including alloisoleucine and tyrosine, rose sharply. Twenty-four hours later, fasting plasma ammonia had fallen from the preinfusion value of 0.050 to 0.028 mM. Protein intake was kept at 0.5 g per kilogram for two weeks. Addition of keto acids by mouth reduced plasma ammonia and alanine to normal or near normal levels. Seizures and episodes of vomiting and lethargy decreased in frequency. Urinary nitrogen decreased, suggesting that nitrogen balance improved. These data indicate that keto acids may be useful in the treatment of congenital hyperammonemia.
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PMID:Treatment of carbamyl phosphate synthetase deficiency with keto analogues of essential amino acids. 16 4

Brain levels of tyrosine, dopamine (DA), noradrenaline (NA), tryptophan, 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were measured after 30, 60 and 120 min of sustained seizure activity, induced in paralyzed, artificially ventilated and anaesthetized (70% N2O) rats by administration of bicuculline (1.2 mg/kg i.v.). In separate animals the rates of accumulation of DOPA and 5-hydroxytryptophan (5-HTP) were estimated in three different brain regions after blockage of the aromatic L-amino acid decarboxylase with NSD 1015 (100 mg/kg). The tissue level of NA was markedly reduced at 30 min and remained low during 120 min of sustained epileptic seizures. In contrast, the DA concentration, being essentially unaffected at 30 min, continuously increased during the following 90 min. 5-HT decreased significantly after 30 min but returned to control levels following 60 and 120 min of seizure activity. The 5-HIAA concentration progressively increased. In all three brain regions (striatum, limbic forebrain and hemispheres) the rate of tyrosine hydroxylation increased. Tryptophan hydroxylation showed a significant increase only in the limbic forebrain. The results suggest that bicuculline-induced seizures lead to an increased functional activity in NA neurons and, at least initially, also in 5-HT neurons. In contrast, DA neurons appear to be inhibited.
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PMID:Monoamine metabolism during bicuculline-induced epileptic seizures in the rat. 30 80

Two infant siblings with modest elevations of serum phenylalanine concentrations had seizures and developmental regression: they died in their second year. Dihydropteridine reductase activity, which can be measured in normal cultured skin fibroblasts, was measured in the younger sibling and was absent. Parents of the two siblings and parents of a previously reported patient all showed 50% or less of the normal dihydropteridine reductase activity in their cultured fibroblasts. Dihydropteridine reductase activity is also present in normal cultured amniotic fluid cells, offering the possibility of prenatal diagnosis. Absence of dihydropteridine reductase results not only in a defect in the conversion of phenylalaning to tyrosine, but also in the biosynthesis of the neurotransmitters, dopamine, norephinephrine, and serotonin. Since deficiencies in these neurotransmitters would not be alleviated by a phenylalanine-restricted diet, it is important to establish the nature of the enzymatic defect in all suspected variants of phenylketonuria.
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PMID:Hyperphenylalaninemia due to dihydropteridine reductase deficiency. Assay of the enzyme in fibroblasts from affected infants, heterozygotes, and in normal amniotic fluid cells. 97 23

Mice with a genetically determined susceptibility to audiogenic seizures were utilized to analyze the ontogeny of central monoamine neurotransmission in relation to a behavior with age-specific properties. Levels of noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) were measured in forebrain and hindbrain regions at 14, 21, 28, and 42 days postnatal age in genetically sensitive or resistant strains of mice. An in vivo estimate of tyrosine and tryptophan hydroxylase activity was obtained at the same ages by following the accumulation of 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) respectively, after the administration of a centrally effective L-amino acid decarboxylase inhibitor (R04-4602, 800 mg/kg). At 14 days, there was a faster rate of accumulation of DOPA in both the forebrain and hindbrain of the sensitive mice compared to mice of the nonsensitive strain. At 21 days, the age of maximal sensitivity in the sensitive mice, the levels of NA were significantly lower in both regions of the sensitive mice, but the accumulation of DOPA was similar between strains at this age. There was also a slightly lower level of 5-HT in the forebrain of sensitive mice at 21 days accompanied by a slower rate of accumulation of 5-HTP in this region. In the hindbrain of the sensitive animals however, the rate of accumulation of 5-HTP was faster than in the sensitive strain. At 28 days, some impairment in mechanisms within NA-containing neurons in the sensitive mice was still apparent (including lower NA levels). At 42 days, there were no differences in amine levels, however, the levels of accumulated DOPA and 5-HTP were significantly lower in the sensitive strain. The results suggest that in the sensitive mice, developmental differences in mechanisms of monoamine storage and/or synthesis may exist which could contribute to deficient amounts of physiologically releaseable transmitter.
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PMID:Audiogenic seizures: relation to age and mechanisms of monoamine neurotransmission. 108 62

Duration of postictal coma following maximal electroshock seizure and monoamine levels in the whole brain were measured in mice. Pretreatment with intraperitoneal alpha-methyl-p-tyrosine (alpha-MT), 5-hydroxytryptophane (5-HTP), or intraventricular 6-hydroxydopamine (6-OHDA) prolonged the coma duration, whereas p-chlorophenylalanine (PCPA) did not affect the coma, and L-DOPA tended to shorten the coma and counteracted the effect of alpha-MT. When the shock was repeated five times with one hour intervals, the duration of coma was progressively increased being accompanied by elevated serotonin (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) levels in the brain. In alpha-MT treated group, a striking parallelism was remarked between coma prolongation and norepinephrine (NE) or dopamine (DA) reduction. These data suggest that prolongation of postictal coma is correlated with reduced NE and DA levels and/or with elevated 5-HT and 5-HIAA levels in the brain.
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PMID:Correlation between brain monoamine levels and postictal coma following electroshock. 115 19

GABAA receptors are multisubunit inhibitory chloride channels in the brain which open in response to binding of gamma-aminobutyric acid (GABA) and are thought to be involved in some forms of seizures. We compare the sequence and expression of the GABAA receptor delta subunit in audiogenic seizure prone (DBA/2J) and seizure resistant (C57BL/6J) inbred strains of mice and also report this subunit's postnatal developmental profile. We did not detect any unique features in the delta subunits of DBA/2J mice which might explain their seizure susceptibility, but did detect in some clones from both DBA/2J mice and C57BL/6J mice an unusual substitution of His for a conserved Tyr in the delta subunit's first putative transmembrane region.
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PMID:Strain comparisons and developmental profile of the delta subunit of the murine GABAA receptor. 132 97

Tyrosine, tryptophan, and their metabolites in the brain of ddY, non-stimulated El (El (-)), and stimulated El (El (+)) mice were measured using the three dimensional HPLC. The tryptophan content was lower in El (+) than ddY and El (-) mice. The 5-hydroxytryptophan content was much higher in both El groups. The serotonin content of El (+) was higher than that of ddY and El (-) mice. The kynurenine content was remarkably high in the El mice. The dopamine content was lower in El (-) than in ddY mice, whereas it was greater in El (+) than in El (-) mice. The norepinephrine showed higher levels in El (+) mice. These facts suggest that El mice possess congenital metabolic abnormalities of tryptophan and tyrosine and that kynurenine may play an important role as convulsant in El mice seizures along with changes in serotonin, dopamine, and norepinephrine that are inhibitory agents and responded to the repetitive convulsions.
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PMID:Regional distribution of tyrosine, tryptophan, and their metabolites in the brain of epileptic El mice. 140 65

Intracerebral microdialysis combined with electrocorticographic recordings was used in a patient subjected to epilepsy surgery. The patient developed a series of partial seizures during an 8 min period. Marked elevations of aspartate (79-fold), glycine (21-fold), glutamate (16-fold) and serine (8-fold) dialysate concentrations occurred in association with onset of the period with seizures. Recurrent seizures occurred, in spite of normalizing amino acid levels. Other amino acids analyzed (aspargine, threonine, arginine, alanine, taurine, tyrosine, phenylalanine, isoleucine and leucine) showed less pronounced changes (1-5 times the basal levels).
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PMID:Seizure related elevations of extracellular amino acids in human focal epilepsy. 140 96


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