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

Pretreatment of rats with the excitatory amino acid antagonist 2-amino-7-phosphonoheptanoic acid (2-APH; 0.5 mmol/kg, i.p.) protected against insulin-induced clonic seizures. Complete protection was observed in 38% of the rats and partial protection in an additional 50%. Lesioning of the corticostriatal pathway by frontal cortical ablation caused decreases in the striatal levels of aspartate (-28%) and glutamate (-18%), an increase in striatal glutamine level (45%), and decreased high-affinity uptake of D-[3H]aspartate (-27%) in the lesioned dorsal neostriatum. Insulin-induced hypoglycemia caused a predicted sharp increase in aspartate level (165%) and decreased glutamate (-20%) and glutamine (-38%) levels in the intact striatum. Pretreatment of rats with 2-APH significantly reversed the insulin-induced changes in striatal aspartate, glutamate, and glutamine levels, especially in the intact hemisphere. In normoglycemic control rats, the "metabolic," i.e., concentration in the lesioned hemisphere, aspartate pool constituted 72% and the "synaptic," i.e., the concentration difference between the intact and lesioned hemispheres, 28% of the total striatal aspartate pool. 2-APH had no effect on the level of "metabolic" aspartate in the striata of normoglycemic rats but caused an almost complete suppression of "synaptic" aspartate. Following insulin-induced hypoglycemia, the "metabolic" aspartate pool doubled, whereas the "synaptic" aspartate pool increased 3.5-fold in the absence of 2-APH. The insulin-induced rise in "synaptic" aspartate level was almost completely blocked by 2-APH (a 5% rise instead of a 3.5-fold rise).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:2-Amino-7-phosphonoheptanoic acid inhibits insulin-induced convulsions and striatal aspartate accumulation in rats with frontal cortical ablation. 329 20

Biochemical and pharmacological effects of gamma-vinyl GABA (Vigabatrin, GVG), and irreversible enzyme-activated inhibitor of 4-aminobutyrate: 2-oxoglutarate aminotransferase (EC 2.6.1.19; GABA-T), were measured in mice. This anticonvulsant produced a time- and dose-dependent elevation of the GABA, phenylalanine and lysine contents of cortical tissue and simultaneously decreased glutamate, aspartate and alanine levels. In addition, GVG caused a biphasic change in glutamine concentrations (a decline 1-4 hours after administration, followed 20 hours later by an increase). Moreover, we found a new, as yet unidentified amino acid in the brain eluting with the same retention time as alpha-aminoadipic acid from an HPLC cation-exchange column. The level of this novel chemical entity was greatly increased by GVG 20 hours after injection of the drug. At all tested intervals between 1 and 60 hours after injection, GVG was ineffective against maximal electroshock. The GABA-T inhibitor dose-dependently protected mice against isoniazid-induced seizures, simultaneously causing an increase in brain GABA concentrations. However, this apparent correlation applied only until 4 hours after treatment. To better define the anticonvulsant profile of GVG, groups of mice were treated, 1, 2, 4, and 24 hours prior to challenge with convulsant doses of strychnine, pentetrazole (PTZ), and picrotoxin, and brain amino acid levels, including brain concentrations of GVG, were measured. In all instances, the time dependency of the anticonvulsant effects of GVG and of increases in brain GABA levels differed. Amino acid concentrations in animals treated only with GVG were similar to those in animals given GVG and a chemical convulsant. GVG showed no selectivity for seizures produced by impairment of GABA-ergic neurotransmission. Although GVG is an effective GABA-T inhibitor, it apparently affects several other pyridoxal-phosphate-dependent cerebral enzymes and/or interacts with other neurotransmitter systems as well.
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PMID:Gamma-vinyl GABA: comparison of neurochemical and anticonvulsant effects in mice. 341 34

Rats were rapidly kindled with electrical stimuli to the hippocampus, and the concentrations of GABA and related amino acids were measured in several brain regions, both in the baseline kindled state and during active seizures. In the baseline kindled state, a consistent pattern was found throughout the hippocampus where GABA levels were depressed and glutamate and glutamine levels were elevated. During seizures GABA rose slightly while glutamate and glutamine increased to twice control values. These changes were seen to various degrees in other brain areas. Turnover in the GABA-glutamate-glutamine cycle was measured in kindled rats experiencing seizures and compared to control animals. During seizures there was an increased turnover of the excitatory compounds glutamate and aspartate relative to GABA. The data indicate that kindling produces a change of presynaptic GABA metabolism which results in diminished inhibition.
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PMID:Alterations in neurotransmitter amino acids in hippocampal kindled seizures. 350 7

The effects on hippocampal extra- and intracellular amino acids of focal injection of folic acid into the amygdala in the rabbit were studied with brain dialysis. Folate seizures were accompanied by pronounced elevations of extracellular alanine and phosphoethanolamine. The increase of extracellular alanine was related to an enhanced level of this amino acid in total hippocampal tissue, whereas phosphoethanolamine was unaltered in tissue biopsies. Folate seizures did not significantly affect extracellular aspartate and extracellular glutamate was only slightly elevated (50-75% over baseline values). The tissue concentration of glutamate remained at control levels during the seizures and tissue aspartate was decreased by 28%. Extracellular glutamine decreased rapidly after folate injection with a concomitant increase of total hippocampal glutamine. Neither extra- nor intracellular taurine was affected by folate epilepsy. The experiments also encompassed measurements of the extracellular purine catabolites inosine, hypoxanthine and xanthine. Folic acid-induced epilepsy produced changes in these compounds indicative of moderately accelerated degradation of adenosine 5'-triphosphate. The findings support the view of glutamate as a mediator of epilepsy-related brain damage. It is, however, questionable if the small enhancement of extracellular glutamate is enough to provoke neuronal necrosis associated with folate epilepsy.
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PMID:Alterations in hippocampal extracellular amino acids and purine catabolites during limbic seizures induced by folate injections into the rabbit amygdala. 367 May 97

The omega-phosphono-alpha-aminocarboxylic acids, e.g., 2-amino-5-phosphonopentanoate and 2-amino-7-phosphonoheptanoate, are known to act as potent and selective antagonists at N-methyl-D-aspartate receptors and to have a pronounced anticonvulsant action on a variety of animal models of epilepsy. In the present study, the effects of these omega-phosphono-alpha-aminocarboxylic acids on E1 mice were investigated. These mice are inbred mutant epileptic mice, which are highly susceptible to convulsive seizures upon throwing stimulation. 2-Amino-3-phosphonopropionate injected intraventricularly (at a dose of 1.04 mumol) had a marked anticonvulsant action, but at a lower dose (0.1 mumol), it induced running fits. 2-Amino-4-phosphonobutyrate induced transitory excitation just after the injection, followed by sedation. 2-Amino-5-phosphonopentanoate induced marked behavioral sedation. 2-Amino-6-phosphonohexanoate induced tonic-clonic convulsions and epileptic discharges in electroencephalograms. 2-Amino-7-phosphonoheptanoate showed a strong anticonvulsant action at a dose of 1.27 mumol, but it induced myoclonic seizures at a lower dose. Amino acid analyses of E1 mouse brain showed that 2-amino-3-phosphonopropionate increased the glutamine level, 2-amino-4-phosphonobutyrate decreased the aspartic acid level, 2-amino-5-phosphonopentanoate decreased the glutamic acid level, 2-amino-6-phosphonohexanoate decreased the glutamic acid, glutamine, gamma-aminobutyric acid, glycine and alanine levels, and 2-amino-7-phosphonoheptanoate decreased the glutamic acid label 1 hour after their injection. These findings suggest that the effects of omega-phosphono-alpha-aminocarboxylic acids on the E1 mouse brain are multiple and complicated, depending on the numbers of their carbon chain.
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PMID:The effect of omega-phosphono-alpha-aminocarboxylic acids on seizures and brain amino acid levels in E1 mice. 367 86

Using tritium-labelled 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO) its tissue distribution and metabolism were investigated in adult mice and 4-day-old chicks after systemic administration of the drug. It was found not to be significantly metabolized in the brain since metabolites of THPO corresponding to only approximately 8% of the parent compound could be detected 30 min after administration of the drug intramuscularly in mice. In the liver, however, THPO was found to be metabolized to a considerable extent. In chicks THPO metabolites were found in the brain but they accounted for less than 35% of the radioactivity. The brain concentration of THPO in mice and chicks corresponded to respectively 10 and 50% of the dose injected intramuscularly and the tissue level was essentially constant for at least 3 h after injection. Following systemic administration of THPO to mice and chicks the contents of aspartate, glutamate, glutamine, and gamma-aminobutyric acid (GABA) in whole brain and in synaptosomes was determined. It was found that only GABA contents were affected being increased in synaptosomes from mice and decreased in whole brain in chicks. Doses of THPO, which in chicks but not in mice led to brain levels that were sufficient to inhibit glial GABA uptake, were found to protect chicks but not mice against isonicotinic acid hydrazide-induced seizures. The findings are compatible with the notion that THPO exerts its anticonvulsant activity by inhibition of astrocytic GABA uptake.
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PMID:Tissue distribution, metabolism, anticonvulsant efficacy and effect on brain amino acid levels of the glia-selective gamma-aminobutyric acid transport inhibitor 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol in mice and chicks. 373

Evidence of genetic factors in seizure disorders by examination of plasma amino acid concentrations in multiply affected sibships was investigated. The strategy of multiply affected sibship ascertainment was used to reduce heterogeneity as one of several potential sources of variation in quantitative amino acid levels. Our results do not support previously reported increases in plasma taurine, aspartic acid, or glutamic acid in seizure patients. However, we do find that multiply affected sibships have significantly elevated plasma concentrations of arginine and asparagine, and significantly decreased ornithine. These amino acid concentrations may be under quantitative genetic control. Within-sibship comparisons indicate that seizure patients have increased glutamine and decreased lysine and phenylalanine, possibly secondary to the seizures. We also find that anticonvulsant use complicates statistical analyses. Further studies to more clearly delineate the genetics of plasma amino acid concentrations (or other quantitative metabolic measures) and their role in seizure disorders are required and will benefit from the use of a homogeneous sampling strategy.
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PMID:Altered amino acid levels in multiply affected sibships with seizures. 407 67

In rabbits, generalized seizures were induced by methoxypyridoxine, and changes in amino acid concentrations of 15 brain regions were investigated before seizure onset and during the course of sustained epileptiform activity. As previously reported, gamma-aminobutyric acid (GABA) concentration decreased preictally in most regions. At the same time, taurine level was elevated in the hypothalamus, thalamus, hippocampus, caudatum, and frontal cortex. After 90 min of seizures, it was significantly decreased in the hypothalamus, periaqueductal grey, substantia nigra, frontal cortex, and cerebellum. Glycine content was reduced preictally only in the substantia nigra; after seizure onset its concentration rose in all brain areas. Glutamate content in the frontal cortex decreased before seizure onset; after 1.5 h of seizures, its concentration in cerebellum, caudatum, and hippocampus was reduced. Aspartate level was decreased in most areas after sustained seizures; in putamen, however, it was elevated. In contrast, glutamine content increased preictally in the superior colliculus and in all brain areas by approximately 200% after 90 min of seizures. Alanine and valine content also rose markedly in most brain areas after prolonged seizures, and threonine showed the same tendency. The single brain regions were observed to respond to methoxypyridoxine in highly individualistic ways. For example, the glycine content of the substantia nigra, which is believed to utilize this amino acid as a neurotransmitter, decreased preictally. The potential importance of the superior colliculus in seizure induction is considered in view of the early rise in glutamine level. The antagonistic preictal behavior of taurine and GABA is discussed with respect to synthesis, uptake from the blood, and antiepileptic properties.
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PMID:Alterations in the content of amino acid neurotransmitters before the onset and during the course of methoxypyridoxine-induced seizures in individual rabbit brain regions. 613 13

The anticonvulsive effects of GABA, taurine, and glycine were investigated on several chemically-induced and genetic seizure models. Intravenous injections of either GABA, taurine, or glycine provided protection against 3-mercaptopropionic acid (MPA)-induced convulsions in adult Swiss mice. GABA was partially effective against isonicotinic acid hydrazide and was without effect against bicuculline-induced convulsions. Prolonged administration of glycine prevented MPA-induced convulsions but not electrically induced seizures or seizures induced by strychnine or metrazol. Intragastric glycine protected young audiogenic seizure-susceptible DBA/2 mice against all three phases of sound-induced convulsions (wild running, clonic and tonic seizure), but GABA and taurine provided little or no protection. With increase of glycine, the cerebral levels of glutamine and serine also increased, but that of glutamic acid decreased. The endogenous glutamic and glycine levels were slightly higher in the brains of the audiogenic seizure-susceptible DBA/2 mice than in that of the resistant BALB/Cy strain.
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PMID:Anticonvulsant effects of some inhibitory neurotransmitter amino acids. 613 43

The study was centered on the changes in the amino acid content of nerve endings (synaptosomes) induced by drugs that alter the metabolism of glutamate or gamma-aminobutyric acid (GABA), and that possess convulsant or anticonvulsant properties. The onset of seizures induced by various convulsant agents was associated with a decreased content of GABA and an increased content of glutamate in synaptosomes. The concurrent administration of pyridoxine prevented both the biochemical changes and the convulsions. The administration of gabaculine to mice resulted in large increases in the GABA content of synaptosomes that were counteracted by decreases in glutamate, glutamine, and aspartate levels such that the total content of the four amino acids remained unchanged. The administration of aminooxyacetic acid (0.91 mmol/kg) resulted initially in seizure activity, but subsequently in an anticonvulsant action. No simple relationship existed between the excitable state of the brain induced by aminooxyacetic acid and the changes in the synaptosomal levels of any of the amino acid transmitters. A hypothesis was, however, formulated that explained the convulsant-cum-anticonvulsant action of aminooxyacetic acid on the basis of compartmentation of GABA within the nerve endings.
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PMID:Changes in the amino acid content of nerve endings (synaptosomes) induced by drugs that alter the metabolism of glutamate and gamma-aminobutyric acid. 613 19


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