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)

An implanted stimulating device chronically stimulated the left cervical vagus nerve in epileptic patients. Cerebrospinal fluid concentrations of free and total gamma-aminobutyric acid, homovanillic acid, 5-hydroxyindoleacetic acid, aspartate, glutamate, asparagine, serine, glutamine, glycine, phosphoethanolamine, taurine, alanine, tyrosine, ethanolamine, valine, phenylalanine, isoleucine, vasoactive intestinal peptide, beta-endorphin, and somatostatin were measured before and after 2 months of chronic stimulation in six patients. Significant increases were seen in homovanillic acid and 5-hydroxyindoleacetic acid in three patients, and significant decreases in aspartate were seen in five patients. These changes were associated with a decrease in seizure frequency.
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PMID:Neurochemical effects of vagus nerve stimulation in humans. 150 37

Extracellular levels of aspartate (ASP), glutamate (GLU), serine (SER), asparagine (ASN), glycine (GLY), threonine (THR), arginine (ARG), alanine (ALA), taurine (TAU), tyrosine (TYR), phenylalanine (PHE), isoleucine (ILEU), and leucine (LEU) were monitored by using intracerebral microdialysis in seven patients with medically intractable epilepsy, undergoing epilepsy surgery. In association with focal seizures, dramatic increases of the extracellular ASP, GLU, GLY, and SER concentrations were observed. The other amino acids analyzed, including TAU, showed small changes. The results support the hypothesis that ASP, GLU, GLY, and possibly SER, play an important role in the mechanism of seizure activity and seizure-related brain damage in the human epileptic focus.
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PMID:Intracerebral microdialysis of extracellular amino acids in the human epileptic focus. 150 52

In amygdala-kindled rats a deficit in learning brightness discrimination was found. We concluded that this result provides a reliable basis for creating an animal model of cognitive dysfunctions in epileptics. Recently, a des-tyrosine D-amino acid substituted derivative of bovine beta-casein(1-5) was reported to exhibit anticonvulsant as well as antidepressant activity. Therefore, we tested the effect of this peptide on kindled seizures and the learning deficit after kindling. It was found that the peptide suppressed the duration of seizures whereas seizure severity was not influenced. Furthermore, the learning performance of peptide-treated rats was significantly higher than that of kindled controls.
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PMID:dTyr-D-Phe3 (Pro-D-Phe-Pro-Gly) interacts specifically with amygdaloid-kindled seizures and is capable of preventing the learning deficit occurring after kindling. 162 Jun 59

Looking for the 'epilepsy gene', we used ddY derived, genetically seizure-susceptible El mice. To find biochemical abnormalities, we examined the amino acid metabolism and gene activity, including poly(A)+ RNA and sodium channel mRNA expressions, in the developmental growth of El mice. At the early postnatal stage, abnormalities in amino acid metabolism were aberrant free amino acid fluctuations. Almost all free amino acids in the liver of newborn El mice showed considerably lower levels than did ddY mice. Among those amino acids, Asp, Glu and Tyr were extremely low, but rapidly recovered to the ddY level within a week. During the successive growth period, we observed no significant difference in hepatic amino acid levels between El and ddY mice. No such drastic changes were noted in the amino acid levels in the brains of ddY and El mice; only the Gly level was greater in El mice than in ddY mice on the day of birth. Rotatory stimulation which evokes convulsions in El mice but not in ddY mice was applied to adult mice and changes in the amino acid level were assessed. The level of Glu and Tyr in seizure-induced El mice was approximately twice that noted in the liver and brain of El mice, which did not experience seizures. It was also somewhat increased in ddY mice subjected to rotational stress which did not induce seizures in that strain. Gene activity that expresses poly(A)+ RNAs, including sodium channel mRNA, was determined by Northern blot analysis, which reveals unscheduled mRNA synthesis by the appearance of an extra band approximately 3 kb in size.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Unusual biochemical development of genetically seizure-susceptible El mice. 166 88

The present experiments investigated if dorsal pontine tissue obtained from 16-day postconception rat fetuses and stereotaxically transplanted into the dorsal hippocampus or third ventricle of genetically epilepsy-prone rats (GEPRs) would alter the expression of audiogenic seizures. Of eight GEPR-9s receiving pontine-tissue grafts bilaterally into the dorsal hippocampus, none showed any reduction in AGS severity. In contrast, three of five GEPR-9s receiving grafts into the third ventricle eventually displayed a decreased seizure severity following transplantation. Of five GEPR-3s receiving transplants into the hippocampus, one animal showed a gradual and significant reduction in seizure severity after transplantation. Tyrosine-hydroxylase (TH) immunohistochemistry showed that transplanted tissue contained abundant TH-immunoreactive profiles including perikarya and fibers. The results of these preliminary studies suggest that the GEPR model of epilepsy may be useful in studying the corrective potential of neurotransplants.
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PMID:Intracerebral grafting of fetal dorsal pons in genetically epilepsy-prone rats: effects on audiogenic-induced seizures. 167 95

1. Sodium di-n-propylacetate (DPA) treatment induced significant increases in brain contents of gamma-aminobutyric acid (GABA), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA). Furthermore, the threshold for pentylenetetrazol (PTZ) clonic convulsions was also increased in response to DPA administration. 2. Pretreatment with inhibitors of monoamine synthesis alpha-methyl-p-tyrosine (AMPT) and p-chlorophenylalanine (PCPA) did not alter the anticonvulsant activity of DPA, but when given alone, both AMPT and PCPA caused significant decreases in brain monoamine contents and PTZ threshold seizures. 3. Experiments using probenecid suggest that the increases in 5-HIAA and HVA seen after DPA treatment could have resulted from inhibition of their active transport out of the brain. These data indicate that the anticonvulsant action of DPA is not dependent on changes in monoamine metabolism in the brain.
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PMID:Anticonvulsant activity of di-n-propylacetate and brain monoamine metabolism in the rat. 169 53

Phosphorylation of protein tyrosines is an important modulatory process for cell signaling and other cellular functions. Rat brain regions were examined for altered protein phosphotyrosines, using Western blot analysis and microwave irradiation to limit postmortem alterations, after administration of two convulsants: lithium plus pilocarpine or kainic acid (KA). Most phosphotyrosine proteins were unaltered by these treatments, but there was a large, specific increase in the tyrosine phosphorylation of a 40-Kd protein. This increase was evident in all three regions examined: cerebral cortex, hippocampus, and striatum; it occurred abruptly with onset of generalized status epilepticus (SE) and remained elevated for at least 90 min. Most of the tyrosine phosphorylated 40-Kd protein was in the cytosolic fraction. These results demonstrate a large, specific effect of chemically induced seizures on a single phosphotyrosine protein in rat brain.
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PMID:Seizure-induced protein tyrosine phosphorylation in rat brain regions. 172 Jul 36

This study extends our previous work in which we described the presence of an interictal behavioral disturbance in a chronic animal model of temporal lobe epilepsy (TLE). In this study, we investigated the cerebrospinal fluid (CSF) neurotransmitter changes underlying the development of chronic recurrent seizures of temporal lobe origin and interictal behavioral disturbance in cats made epileptic after intrahippocampal injection of kainic acid (KA). Using high-performance liquid chromatography, we measured 22 putative neurotransmitter amino acids. After intrahippocampal KA injection, cats developed an initial acute period of intense seizure activity. Cisternal CSF amino acids, which were repeatedly sampled during the acute period through a permanent indwelling cannula, were unchanged apart from a mild elevation in CSF alanine. The high-level seizure activity gradually decreased, and cats entered a chronic epileptic period characterized by recurrent yet intermittent temporal lobe seizures. CSF GABA levels during the chronic epileptic period were significantly decreased. In contrast, CSF levels of other amino acids--alanine, tyrosine, taurine, aspartic acid, and glutamic acid--did not change significantly. Behavioral testing also showed a heightened interictal defensive reactivity during the chronic epileptic period. To the extent that CSF GABA concentration reflects brain GABA concentration, this study suggests that a decrease in brain GABA may contribute both to the epilepsy and interictal emotional lability of animals with a chronic seizure disorder of temporal lobe origin.
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PMID:Interictal behavioral alterations and cerebrospinal fluid amino acid changes in a chronic seizure model of temporal lobe epilepsy. 174 47

Male rats were treated by oral intubation with tyrosine (Tyr), at doses of 0.5 and 1.0 g/kg body weight, alone or together with 1 g aspartame (APM)/kg body weight, or an equivalent dose of phenylalanine (Phe; 0.5 g/kg body weight); the effects on seizures induced by an effective dose of metrazol (ED50) were observed. Tyr (0.5 g/kg body weight) had a protective effect against the Phe-potentiation of metrazol-induced clonic-tonic convulsions. At the same dose Tyr had no effect on the seizure-promoting activity of APM, but at 1 g/kg it reduced the proconvulsant potential of the sweetener. Analysis of the brain and plasma amino acid concentrations indicated that the Tyr to Phe ratio tended to be enhanced in Tyr-Phe treated rats compared with those treated with Phe alone. This ratio remained essentially constant in the brain of APM-treated rats, compared with those treated with APM plus 1 g Tyr/kg body weight, whereas an increase in this ratio in the plasma was observed. These results confirm that Tyr antagonizes the proconvulsant effect of Phe and APM and they further suggest that no simple relationship exists between the relative brain concentrations of the two amino acids and the response to metrazol convulsions.
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PMID:Effect of tyrosine on the potentiation by aspartame and phenylalanine of metrazol-induced convulsions in rats. 176 32

Influences of the manipulation of brain catecholaminergic neuronal activity on the incidence of lidocaine-induced convulsions in mice were studied and compared with those of pentylenetetrazol (PTZ)-induced convulsions. alpha-Methyl-p-tyrosine (alpha-MPT) decreased both brain noradrenaline (NA) and dopamine (DA) levels, and disulfiram decreased the NA level and increased the DA level. The incidence of lidocaine-induced convulsions was decreased by treatments with alpha-MPT and disulfiram, while that of PTZ was increased by either treatment. The incidence of lidocaine-induced convulsions was slightly, but not significantly increased by L-dihydroxyphenylalanine (L-DOPA), although the brain DA level was increased by L-DOPA. Methamphetamine and desipramine increased the incidences of lidocaine-induced convulsions. These results may suggest that brain catecholaminergic neurons, differing from their role in inhibiting control of PTZ-seizure, act to facilitate lidocaine-induced convulsions.
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PMID:Changes in convulsion susceptibility of lidocaine by alteration of brain catecholaminergic functions. 188 Sep 90


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