Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basal and high potassium-stimulated release of endogenous amino acids was measured using brain dialysis in the hippocampus of urethane-anesthetized seizure-resistant (SR) and seizure-susceptible (SS) rats. Moreover, the tissue level of amino acids was determined in the hippocampus, sensorimotor cortex, cerebellum and corpus striatum. The basal extracellular concentration of amino acids did not differ between SR and SS rats. However, aspartate release was higher, and taurine and phosphoethanolamine release was lower in SS rats during stimulation with 100 mM K+. Several strain differences were observed with regard to regional tissue levels of amino acids. Aspartate was significantly elevated in the hippocampus, cortex and cerebellum of SS animals, and the catecholamine precursor tyrosine was diminished in all regions examined. Other disparities included a depressed gamma-aminobutyrate concentration in the hippocampus and cortex, slightly increased levels of phosphoethanolamine in the cerebellum and minor decreases in striatal and cortical taurine. Glutamate, glutamine, serine and alanine concentrations were not significantly altered in any brain area of the SS rat. The results confirm and extend previous findings on abnormalities in aspartate, taurine and phosphoethanolamine regulation in this model. In addition, decreased availability of tyrosine may provide a partial explanation for the well-documented deficiency in cerebral norepinephrine in the SS strain.
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PMID:Abnormalities in the levels of extracellular and tissue amino acids in the brain of the seizure-susceptible rat. 270 50

Several factors involved in the regulation of ornithine decarboxylase (ODC) activity in adult rat brain tissue have been identified by using the in vitro hippocampal slice preparation. The same amino acids that have previously been reported to induce ODC in tissue culture, i.e., asparagine and glutamine, were found to produce a concentration- and time-dependent increase in ODC activity that reached a 100 fold the control value after 6 h of incubation. The effect of asparagine was totally blocked by inhibition of either protein or RNA synthesis, suggesting that the inducing amino acids increase ODC activity by stimulating the transcription of genes directly or indirectly regulating ODC activity. The effect of the inducing amino acids was potentiated by a variety of factors which by themselves did not modify ODC activity. In particular, opioid peptides markedly potentiated the effect of asparagine. Although the opiate antagonists naloxone and naltrexone totally blocked the effects of the opioid peptides on ODC induction, they also produced an inhibition of the asparagine-mediated increase in ODC activity. Other factors like dibutyryl cyclic AMP and insulin also potentiated the effects of asparagine on ODC activity. These results provide the first description of ODC induction in an in vitro preparation of adult brain tissue and indicate that the hippocampal slice preparation could be used to study the molecular mechanisms which regulate the expression and activity of ODC in the adult central nervous system. Moreover the data suggest possible mechanisms which may be involved in the induction of ODC in hippocampus by seizure activity.
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PMID:Induction of ornithine decarboxylase in adult rat hippocampal slices. 285 84

Vigabatrin (gamma-vinyl GABA) is a new anticonvulsive drug that irreversibly inhibits the activity of GABA transaminase. The effect of vigabatrin on neurotransmission-related amino acids in CSF of 28 epileptic patients was studied and the relationship between the amino acid pattern and clinical response during 7 months of administration of vigabatrin. Of this study population, 46% had more than 50% decrease in seizure frequency (responders). In 54% the seizures decreased less than 50% (nonresponders). In the whole study group, the levels of total GABA during vigabatrin treatment were 283%, free GABA 197%, homocarnosine 310% and glycine 128% that of the levels at baseline in the same patients. Glutamate, glutamine, aspartate, asparagine, and taurine concentrations did not change. The amino acid pattern in CSF during administration of vigabatrin did not differ significantly in responders and nonresponders. The study suggests that both GABAergic and glycinergic neurotransmission are affected by vigabatrin. The changes in CSF levels of neurotransmitter amino acids are, however, not necessarily related to the clinical response.
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PMID:Effect of vigabatrin (gamma-vinyl GABA) on amino acid levels in CSF of epileptic patients. 285 6

Measurement of glucose utilization after 20 minutes of seizure activity induced by the systemic administration of convulsants in paralyzed, ventilated rats demonstrates that the initial metabolic activation during kainic acid seizures is confined to the hippocampus. L-allylglycine-induced generalized seizures result in a global metabolic activation, whereas bicuculline seizures in fasted rats have little effect on brain glucose utilization after 20 minutes of seizure activity. Other metabolic changes associated with kainic acid seizures also predominate in the hippocampus, were decreases in the levels of aspartate, glutamate, taurine and glutamine, and an increase in the level of GABA are observed after 20 minutes of seizure activity. L-allylglycine seizures are associated with generalized decreases in regional GABA levels, and increases in regional glutamine levels. Bicuculline-induced changes include increases in hippocampal GABA and taurine levels, and increases in cerebellar glutamine and taurine levels. These changes can be tentatively explained in terms of known biochemical and neurophysiological mechanisms of these convulsants.
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PMID:Regional changes in transmitter amino acids during focal and generalized seizures in rats. 286 90

Changes in amino acid concentrations were investigated in selected regions of rat brain prior to the onset and during the course of epileptiform seizures induced by L-homocysteine. The concentration of gamma-aminobutyric acid (GABA) decreased preictally in substantia nigra (-18%), caudate putamen (-26%), and inferior colliculus (-46%). After seizure onset, the GABA content was further reduced in substantia nigra (-31%) and additionally in hippocampus (-18%). Preictal taurine levels were elevated in globus pallidus (+26%) and caudate putamen (+13%) but returned to normal after seizure onset. However, in hippocampus, taurine decreased both preictally (-22%) and after seizure onset (-56%). Glycine was reduced preictally only in globus pallidus (-13%). After seizure onset the direction of its concentration change varied in the brain regions studied. Glutamate levels decreased preictally in hippocampus (-10%) and hypothalamus (-46%) but increased in globus pallidus (+14%). Normal levels were detectable after seizure onset in hypothalamus and globus pallidus but a further reduction in hippocampus (-59%) and significant reductions in substantia nigra (-15%) and caudate putamen (-17%) were detected. Aspartate was elevated in hippocampus, both preictally (+49%) and after seizure onset (+21%) while at the same phases in globus pallidus a consistent reduction (-30%) was observed. The glutamine content increased preictally in globus pallidus (+41%) and hypothalamus (+36%), and in all brain areas during the ictal phase of seizure, the hippocampus exhibiting a dramatic increase (approximately 300%). The contents of serine and alanine were altered in most regions studied only after seizure onset, with the exception of the hippocampus, where a decrease (-41%) of serine was observed preictally.
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PMID:Differential changes in the content of amino acid neurotransmitters in discrete regions of the rat brain prior to the onset and during the course of homocysteine-induced seizures. 287 Jan 35

Epilepsy is an ancient disorder which treatment over the centuries has been guided by preconceptions regarding its origin. The major improvements in epilepsy management came following the discovery of the EEG and the development of seizure suppressing agents. These advances in diagnosis and anticonvulsant therapy have further ingrained the conviction that epilepsy is a disease of neurons. Evidence presented here is intended to support a different point of view which suggests that the metabolic modifications in epileptogenic tissue denote subtle alterations in the anatomical and biochemical relationship between neurons and their glial envelopes. As a result the extracellular environment of these cells contain higher than normal levels of glutamic acid. This creates an unnatural functional connectivity between neurons so that they establish abnormal synchronous activity between them and become hyperexcitable due to the depolarizing milieu. To compensate for these biochemical changes it is suggested that some thought might be given to epilepsy management by metabolic manipulation. The measures should be directed specifically towards improving the ability of glia to remove glutamic acid from the extracellular milieu. Two obvious possibilities are to enhance glial glutamine synthesis and to improve the interstitial "wash-out" of glutamic acid in epileptogenic epicenters. Such a therapy would anticipate to gradually diminish seizure incidence and susceptibility without, however, having a direct action on convulsive episodes per se. The approach must be considered an adjunct to current epilepsy treatment and not a substitute for the use of anticonvulsants.
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PMID:Contributions of basic neurochemistry towards a novel concept of epilepsy. 288 91

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 effect of chronic administration of gamma-vinyl GABA (GVG; vigabatrin) on levels of neurotransmission-related amino compounds was studied in lumbar cerebrospinal fluid of 65 patients with complex partial epilepsy. The first sample of cerebrospinal fluid was taken before a 3-month period of treatment with 3 g gamma-vinyl GABA/day, and the second was taken afterwards. From patients who showed a greater than 50% reduction in seizures (responders) or marked improvement in global performance, a third sample was taken at the end of the next 3-month phase, during which 3 g or 1.5 g gamma-vinyl GABA had been administered daily. During treatment with 3 g gamma-vinyl GABA/day, 55% of the patients showed more than 50% reduction in complex partial seizures; and at the same time free GABA, total GABA, homocarnosine, and glycine concentrations in the cerebrospinal fluid increased by 104%, 151%, 194% and 16%, respectively. After reduction of the daily dose to 1.5 g, the levels of free GABA, total GABA and homocarnosine were still increased by 65%, 115% and 102%, respectively. gamma-Vinyl GABA correlated with the levels of free GABA (P less than 0.002) and glycine (P less than 0.001). Concentrations of homocarnosine at baseline and homocarnosine and total GABA during gamma-vinyl GABA treatment were lower (P less than 0.005) in the group of non-responders than in the responder group. Glutamic acid, glutamine, aspartic acid, asparagine, and taurine levels did not change during gamma-vinyl GABA treatment. In conclusion, administration of gamma-vinyl GABA reduces epileptic seizures and produces dosage-dependent increases in levels of free GABA, GABA-containing peptides and of glycine in cerebrospinal fluid, without concomitant change in levels of excitatory amino acids.
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PMID:Inhibitory and excitatory amino acids in CSF of patients suffering from complex partial seizures during chronic treatment with gamma-vinyl GABA (vigabatrin). 314 62

The extracellular content of taurine, glutamate, glutamine, and glycine was measured by the novel method of brain dialysis in the acute phases following an intrahippocampal injection of the excitotoxic convulsant brain metabolite quinolinic acid (QUIN). Using bilaterally implanted depth electrodes physically combined with hollow fibers for dialysis, it was possible to collect continuously brain perfusates while simultaneously monitoring brain activity in the unanesthetized rat. In separate animals, hippocampal amino acid tissue levels were measured 2 h after an intracerebral injection of a convulsant dose (156 nmol) of QUIN. When compared with those in animals receiving the nonconvulsant decarboxylation product of QUIN, nicotinic acid, no differences in tissue levels were detected. In contrast, the same dose of QUIN caused a selective increase (2.24-fold) in taurine levels in perfusates from the injected hippocampus. These changes were apparent prior to the onset of electrographic seizures and did not occur in the contralateral hippocampus where seizure activity was equally severe. Thus, increases in extracellular taurine, triggered by the presence of QUIN in the hippocampus, may reflect a selective tissue response to the neurotoxic (rather than the convulsant) effects of this excitotoxin.
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PMID:In vivo brain dialysis of amino acids and simultaneous EEG measurements following intrahippocampal quinolinic acid injection: evidence for a dissociation between neurochemical changes and seizures. 315 48

The effect of diazepam on inbred mutant E1 mice, which develop convulsive seizures after repeated sessions of being tossed up, was examined. Acute administration of diazepam (32 mg/kg, i.p.) completely inhibited the convulsions. At that time, the dopamine level was increased in the cortex and hippocampus, and the norepinephrine level in the cerebellum was decreased. 5-Hydroxytryptamine levels were not changed. As for amino acids, the glutamine level increased and the levels of GABA, glutamic acid, aspartic acid, alanine and other amino acids were not changed.
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PMID:Depressed convulsions by diazepam and its effects on brain monoamines and amino acids in E1 mice. 319 91


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