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)

An intraperitoneal injection of the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine, did not alter the incidence of seizures induced by pentylenetetrazol, but increased the severity and duration of the tonic and clonic phases which resulted in death of some animals. By contrast, pentylenetetrazol seizures' characteristics were significantly changed in response to the intraperitoneal administration of the norepinephrine antagonist, 6-hydroxydopamine, by abolishing the tonic and clonic phases of the seizure. Moreover, alpha-methyl-p-tyrosine slightly attenuated the protective effect of 6-hydroxydopamine against pentylenetetrazol-induced seizures. Neurochemically, alpha-methyl-p-tyrosine significantly lowered the brain contents of both norepinephrine and dopamine while 6-hydroxydopamine caused no changes in the brain contents of these amines.
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PMID:Differential effects of alpha-methyl-p-tyrosine and 6-hydroxydopamine on pentylenetetrazol seizures in mice. 309 80

Gangliogliomas, dysembryoplastic neuroepithelial tumors (DNT) and glioneuronal malformations are frequently encountered in patients with pharmacoresistant focal epilepsies. In order to characterize the neurochemical profile of these neoplastic and malformative glioneuronal lesions, we have examined the presence of the alpha 1 subunit of the GABAA receptor, the N-methyl-D-aspartate receptor subunit 1 (NR1), glutamate decarboxylase, tyrosine hydroxylase, somatostatin, parvalbumin, and calretinin in 60 gangliogliomas, 11 DNT, 10 tuberous sclerosis-like lesions and 17 non-tuberous sclerosis-like glioneuronal malformations. All DNT and tuberous sclerosis-like lesions, 59 gangliogliomas (98%), and 13 non-tuberous sclerosis-like hamartias (76%) were positive for at least one of the markers. Despite a great variation between and within the different entities, the neurochemical profile was generally reminiscent of normal neocortex: glutamate decarboxylase, GABAA receptor and NR1 which are common in neocortical neurons were present in the great majority of the lesions and often showed high labeling indices. There were three tuberous sclerosis-like lesions (30%) that contained both NR1 and glutamate decarboxylase immunoreactive giant cells in addition to well-differentiated ganglion cells. This supports the idea that at least some of these giant cells are of neuronal origin. The oligodendroglia-like cells of DNT and glioneuronal hamartias did not show immunoreactivity for any of the markers. The very high incidence of ganglioglial lesions in patients with chronic focal epilepsies and the presence of neurotransmitter-producing enzymes, neurotransmitter receptors, neuropeptides, and calcium-binding proteins in many of these lesions suggests that they may play an active role in the pathogenesis of epileptic seizures.
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PMID:Neurochemical profile of glioneuronal lesions from patients with pharmacoresistant focal epilepsies. 766 58

Amino acid and monoamine concentrations were examined in tissue extracts of caudate nucleus of genetic substrains of BALB/c mice susceptible or resistant to audiogenic seizures. Amino acids [aspartate, glutamate, glycine, taurine, serine, gamma-aminobutyric acid (GABA)], monoamines, and related metabolites were separated by isocratic reverse-phase chromatography and detected by a coulometric electrode array system. In situ activity of tyrosine hydroxylase and tryptophan hydroxylase were determined by measuring the accumulation of L-DOPA and 5-hydroxytryptophan after administration of the decarboxylase inhibitor NSD-1015. Highly significant decreases in concentrations of both excitatory (glutamate and aspartate) and inhibitory amino acids (GABA and taurine) were observed in extracts of caudate nucleus of seizure-prone mice. Substantial decreases in concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were also noted. Decreased accumulation of L-DOPA after NSD-1015 administration provided evidence for decreased tyrosine hydroxylase activity and decreased DA synthesis in striatum of seizure-prone mice compared with seizure-resistant mice. Decreased concentrations of the DA metabolite 3-methoxytyramine (after NSD-1015 administration) suggested that DA release was also compromised in seizure-prone mice. No significant difference in 5-hydroxytryptophan accumulation in striatum of seizure-prone and seizure-resistant mice suggested that tryptophan hydroxylase activity and serotonin synthesis were not affected. The data suggest that seizure-prone BALB/c mice have a deficiency in intracellular content of both excitatory and inhibitory amino acids. The data also raise the issue of whether GABAergic interactions with the nigrostriatal DA system are important in the regulation of audiogenic seizure susceptibility.
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PMID:Determination of amino acids and monoamine neurotransmitters in caudate nucleus of seizure-resistant and seizure-prone BALB/c mice. 768 Nov

We present the histologic study of two patients who underwent cerebral cortex resection for partial seizures linked with cortical dysplasia. The distinction of areas of seizure origin from areas of seizure propagation was made according to stereoelectroencephalographic criteria. Samples of epileptogenic tissue were studied by using cytoarchitectonic and immunohistochemical stainings. We mapped the catecholaminergic afferents by employing antisera directed against tyrosine hydroxylase and dopamine-beta-hydroxylase enzymes. The epileptic activity was correlated with the underlying patterns of cytoarchitectonic and immunohistochemical changes. The neuropathological features were focal and consisted of large neurons dispersed through all but the first cortical layer (associated in one case to giant glial cells), of variable disturbance of lamination, of neuronal ectopia in the white matter and of moderate proliferation of small glial cells. Areas of seizure onset coincided with that of dysplastic zones. Both laminar distribution and density of catecholaminergic fibers were altered in the dysplastic cortices (area of seizure onset) and there was an increase in the density of tyrosine hydroxylase-immunoreactive fibers in the surrounding areas of seizure propagation. Our results indicate that these developmental epileptogenic lesions were associated with abnormal neuronal circuitry. They provide evidence at the structural level of the increase in tyrosine hydroxylase activity previously reported in spiking areas of human epileptogenic cerebral cortex and they suggest that catecholamines may contribute toward limiting seizure activity propagation.
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PMID:Altered patterns of catecholaminergic fibers in focal cortical dysplasia in two patients with partial seizures. 784 71

Electroconvulsive seizures (ECS) increase tyrosine hydroxylase (TH) activity in the locus coeruleus (LC) but not in the substantia nigra (SN). To determine whether new enzyme synthesis contributes to the increase in TH activity, we carried out in situ hybridization histochemistry to determine the effect of ECS on TH mRNA levels in the LC and SN. The effect of ECS on neuropeptide Y (NPY) mRNA levels in the LC was also studied because NPY coexists with norepinephrine in the LC neurons and has been implicated in depressive disorders. A significant increase was observed in TH mRNA and NPY mRNA levels in LC neurons in the ECS group. There was no difference between TH or NPY mRNA levels in the left and right LC. No change was observed in TH mRNA expression in the SN compacta or SN reticulata. We conclude that the regionally selective increase in TH activity after ECS is at least partly due to increased gene expression and that NPY gene expression is regulated in a similar fashion following ECS.
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PMID:Electroconvulsive shock increases tyrosine hydroxylase and neuropeptide Y gene expression in the locus coeruleus. 809 48

Neuroanatomical methods were used to determine if cocaine irreversibly injures neurons. Despite acute and chronic high-dose treatments for months that produced stereotyped behavior and seizures, and the use of a sensitive silver impregnation method, we were unable to find any evidence of neuronal damage anywhere in the brain. Since expression of the inducible 72 kDa heat shock protein (HSP72) is a sensitive indicator of potentially toxic neuronal stress, we next determined if cocaine evoked HSP72 expression. Even high doses of cocaine that evoked seizures did not induce HSP72 immunoreactivity anywhere within the brain, whereas kainic acid produced widespread HSP72 immunoreactivity and irreversible injury. Having failed to find indications of frank neurotoxicity, we examined peptide and protein cell marker immunoreactivities in search of cocaine-induced changes. Although cocaine treatment had no obvious effects on the patterns of hippocampal calbindin-D28K, somatostatin-, tyrosine hydroxylase- and parvalbumin immunoreactivities, cocaine reliably altered neuropeptide Y-like immunoreactivity (NPY-LI). Most notably, NPY-LI was expressed in hippocampal dentate granule cells and pyriform cortical neurons, which do not normally express it. Conversely, we noted decreased NPY-LI in dentate hilar neurons that normally do express it. Since both changes in NPY-LI were seen only in cocaine-treated rats that exhibited seizures, the role of seizure activity per se in producing the NPY changes was addressed in normal rats by electrical stimulation of the perforant path. Like cocaine, perforant path stimulation for as little as 15min evoked NPY-LI in granule cells but did not replicate the cocaine-induced decrease in hilar cell NPY-LI. These results suggest that cocaine does not irreversibly injure neurons in the rat, even at doses that induce seizures. However, cocaine produces long-lasting changes in NPY expression that are of unknown functional significance. Our inability to demonstrate cocaine-induced neuronal damage in rats should in no way be taken as evidence of its safety in humans.
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PMID:Cocaine neurotoxicity and altered neuropeptide Y immunoreactivity in the rat hippocampus; a silver degeneration and immunocytochemical study. 835 18

Neurons in rat medulla oblongata with Fos immunoreactivity as a marker of synaptic excitation evoked by pentylenetetrazole-induced seizures were compared with cell populations activated by the stimulation of chemoreceptor and baroreceptor afferent pathways. Chemoreceptors were stimulated by placing rats in a hypoxic gas mixture (7% oxygen) for 2 h. Baroreceptors were activated by phenylephrine-induced hypertension. Seizures and hypoxia induced Fos immunoreactivity in neurons with similar anatomical distributions in the nucleus tractus solitarius, dorsal motor nucleus of the vagus, and ventrolateral medulla. Hypertension was associated with Fos immunoreactivity in an overlapping anatomical distribution compared to seizures and hypoxia, but in a more restricted pattern. A similar proportion of catecholaminergic cells of medulla oblongata (cells immunoreactive for catecholamine synthetic enzymes, tyrosine hydroxylase or phenylethanolamine-N-methyltransferase) had Fos immunostaining after seizures and hypoxia (P > 0.05), while significantly fewer were activated by hypertension (P < 0.05). The majority of tyrosine hydroxylase-immunoreactive cells in caudal ventrolateral medulla were activated by both seizures and hypoxia (mean per cents, 79 and 67%, respectively). Since cell populations activated by seizures and hypoxia are indistinguishable, and a majority of tyrosine hydroxylase-reactive cells in caudal ventrolateral medulla are independently activated by each stimulus, it may be inferred that some impulses originating from seizures and chemoreceptor afferent pathways converge to a common set of neurons. These observations identify neurons in rat medulla oblongata which may mediate the impact of seizures on central processing of chemoreceptor afferent activity.
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PMID:Comparison of neurons in rat medulla oblongata with fos immunoreactivity evoked by seizures, chemoreceptor, or baroreceptor stimulation. 880

Seizure activity has been shown to have differential effects on the terminal content of the monoamines, norepinephrine (NE) and dopamine (DA). Induction of seizure activity reduces the terminal content of NE, while DA levels remain unchanged or slightly elevated. This study examined the effect of the chemoconvulsant pentylenetetrazol (PTZ) on the mRNA expression of regulatory proteins which maintain the terminal content of NE and DA (i.e., synthesis and re-uptake). The areas examined were the noradrenergic neurons of the locus coeruleus (LC) and dopaminergic neurons of the substantia nigra pars compacta/ventral tegmentum area (SNpc/VTA) in the rat. In the LC, PTZ increased mRNA expression of the immediate early gene, c-fos, and mRNA expression of the synthesizing enzyme, tyrosine hydroxylase (TH), and the re-uptake protein, norepinephrine transporter (NET). This effect on TH and NET was observed only 1 day after the administration of PTZ. In contrast, PTZ did not alter the expression of c-fos mRNA in the SNpc/VTA, but reduced the expression of the dopamine transporter (DAT) mRNA. This effect was observed only 1 day after the administration of PTZ. TH mRNA expression in dopaminergic neurons was elevated initially in a manner similar to that observed in the LC. However, the effect of PTZ on TH mRNA expression in dopaminergic neurons was more prolonged (still elevated 3 days later). These results indicate that the chemoconvulsant PTZ has differential effects on the mRNA expression of regulatory systems (TH and neurotransporter proteins) in noradrenergic and dopaminergic neurons.
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PMID:Effect of pentylenetetrazol on the expression of tyrosine hydroxylase mRNA and norepinephrine and dopamine transporter mRNA. 903 Jun 97

Two models of genetically epilepsy-prone rat (GEPR) exist, the GEPR-3 and GEPR-9, GEPR-3 and GEPR-9 share a deficiency in presynaptic norepinephrine (NE) and serotonin (5HT) content in specific regions of the central nervous system (CNS). The presynaptic content of dopamine (DA) does not appear to be altered in either adult GEPR strain compared to Sprague-Dawley (SD) rats, the strain from which the GEPR was derived. Presynaptic content of monoamine neurotransmitters, such as NE, 5HT and DA, are maintained by several regulatory proteins which include: synthesis, re-uptake, release, degradation and vesicular transport. To further characterize the monoamine deficiency observed in the GEPR, the mRNA level of the rate limiting enzymes for the synthesis of NE, 5HT and DA and each of the neurotransporter proteins were measured in seizure-naive GEPR-3, GEPR-9 and SD rats. In the locus coeruleus (LC), the major noradrenergic locus, tyrosine hydroxylase (TH) mRNA level was significantly reduced only in GEPR-9 animals compared to SD rats and GEPR-3, while NE transporter (NET) mRNA was significantly elevated in GEPR-3 compared to SD rats and GEPR-9. TH and DA transporter (DAT) mRNA was measured in the dopaminergic neurons of the substantia nigra pars compacta (SNpc), ventral tegmental area (VTA) and zona incerta (ZI), DAT mRNA level was significantly reduced in all dopaminergic neurons in the GEPR-3 compared to SD rats and GEPR-9, while TH mRNA level was significantly elevated in the SNpc/VTA equally in GEPR-3 and GEPR-9 compared to SD rats. In the ZI, TH mRNA level was significantly reduced in GEPR-3 compared to SD rats and GEPR-9. In the dorsal raphe (DR), a major serotonergic locus, tryptophan hydroxylase (TRH) mRNA level was not significantly different from SD in either strain of GEPR; however, 5HT transporter (SERT) mRNA level was significantly reduced in GEPR-9 in the dorsal and lateral regions of the DR compared in SD rats and GEPR-3. These data indicate that two of the regulatory systems that maintain NE, 5HT and DA content are altered in a differential manner in seizure-naive GEPR-3 compared to seizure-naive GEPR-9, with GEPR-3 showing more alterations in dopaminergic neurons. It is uncertain at the present time how these alterations in mRNA level relate to the enhanced seizure susceptibility of these animals. It was apparent that a straightforward correlation between neurotransmitter loss to transcriptional changes in synthesizing enzymes mRNA or to re-uptake protein mRNA was not observed in noradrenergic and serotonergic neurons. Therefore, the decrease in presynaptic NE and 5HT tissue content in these animals may be due to posttranscriptional modification. In contrast, presynaptic DA tissue content which was unaltered in both strains of GEPR, shows an alteration in TH and DAT mRNA level compared to SD rats in all dopaminergic neurons examined. This indicates a possible involvement of DA in regulating the seizure susceptibility of these animals.
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PMID:Alterations in mRNA expression of systems that regulate neurotransmitter synaptic content in seizure-naive genetically epilepsy-prone rat (GEPR): transporter proteins and rate-limiting synthesizing enzymes for norepinephrine, dopamine and serotonin. 903 38

The effects of valproate on CNS concentrations of gamma-aminobutyric acid (GABA), glulamate (GLU), glutamine (GLN); dopamine (DA), serotonin (5-HT), and metabolites were examined in tissue extracts of caudate nucleus of genetic substrains of Balb/c mice susceptible (EP) or resistant (ER) to audiogenic seizures. Generalized tonic-clonic seizures observed in EP mice were inhibited by valproate, administered 1 h prior to testing, in a dose-response fashion. Concentrations of GABA, GLU, and GLN, which were lower in EP mice than in ER mice, were significantly increased by valproate at doses of 180 and 360 mg/kg. Concentrations of homovanillic acid (HVA) and hydroxyindoleacetic acid (5-HIAA), metabolites of DA and 5-HT, were substantially increased by valproate at these doses. The in situ activity of tyrosine hydroxylase (TH) was not significantly influenced by valproate, whereas a valproate-induced increase in tryptophan hydroxylase (TPH) activity was observed in both striatum and in midbrain tegmentum. The data are consistent with the interpretation that anti-convulsive doses of valproate influences the intraneuronal metabolism of monoamines, GABA, and glutamate concurrently. Valproate's influence on the metabolism of both major inhibitory (GABA) and excitatory (GLY amino acids in striatum could contribute to its anti-convulsive effects in genetically seizure prone mice, as well as to the accumulation of DA and 5-HT metabolites.
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PMID:Effects of valproate on amino acid and monoamine concentrations in striatum of audiogenic seizure-prone Balb/c mice. 914 15

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