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

Behavioural, histopathological and neurochemical changes induced by systemic injection of kainic acid (10 mg/kg, s.c.) were investigated in rats. The most pronounced behavioural changes were strong immobility ("catatonia"), increased incidence of "wet dog shakes", and long-lasting generalized tonic-clonic convulsions. The behavioural symptoms were fast in their onset and lasted for several hours. Two distinct phases of histopathological and neurochemical changes were observed. (1) Early partially reversible changes were seen up to 3 h after kainic acid injection. They consisted of shrinkage and pyknosis of neuronal perikarya together with swelling of dendrites and axon terminals. These changes were accompanied by generalized signs of edema throughout the whole brain. Neurochemically, there was a marked decrease in noradrenaline levels (up to 70%) and an increase in levels of 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid and homovanillic acid (up to 200%) in all analysed brain regions, suggesting a strongly increased firing rate of aminergic neurones during the period of generalized seizures. These histological and neurochemical changes were found in all the brain regions examined; they were greatly reduced or only sporadically seen after 1-3 days, when the animals had recovered from the seizures. (2) Late irreversible changes developed 24 h and later following kainic acid injection. They consisted of incomplete tissue necrosis with loss of nerve cells and oligodendrocytes, demyelination, astroglial scar formation, small perivenous hemorrhages and extensive vascular sprouting. The changes were restricted to the pyriform cortex, amygdala, hippocampus (most pronounced in the CA1 sector), gyrus olfactorius lateralis, bulbus olfactorius and tuberculum olfactorium. Neurochemically, a selective decrease was seen in choline acetyltransferase activity (40%) of the amygdala/pyriform cortex area, and of glutamate decarboxylase activity in the dorsal hippocampus (45%) and amygdala/pyriform cortex (55%). No such changes were found in the frontal cortex and the striatum/pallidum. Since at these later time periods the widespread early changes in monoamine metabolism were mostly normalized, loss of acetylcholine and gamma-aminobutyric acid neurons in the affected brain regions represented a selective neurochemical change typical for this stage of kainic acid action. The observed neurochemical and histopathological changes may be directly related to the excitotoxic and convulsive properties of kainic acid. However, brain edema resulting in herniation damage of the basal portions of the brain in addition to disturbances of microcirculation and +
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PMID:Kainic acid induced seizures: neurochemical and histopathological changes. 614 39

The effects of fluoxetine [an inhibitor of 5-hydroxytryptamine (5-HT) reuptake] on electrically-induced spinal cord seizures were determined by monitoring alterations in the total duration of seizure, as well as the durations of tonic flexion and extension. The capacity of fluoxetine to inhibit 5-HT reuptake in the spinal cord was confirmed by measurements of 5-hydroxyindoleacetic acid (5-HIAA) content. When given in a dose of 10 mg/kg, fluoxetine failed to produce an effect on spinal cord seizures or on 5-HIAA content. However, a dose of 20 mg/kg did significantly reduce 5-HIAA content although it did not alter seizure activity. These results further support our earlier suggestion that 5-HT containing neurons in the spinal cord do not modulate electrically-induced seizures.
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PMID:Effects of fluoxetine on electrically-induced spinal cord seizures in rats. 615 71

When studying the role of the locus coeruleus (LC) in the regulation of seizure susceptibility in rats, we found that bilateral LC lesion significantly lowered the electroshock seizure threshold for the tonic extension of forelegs. The pattern of maximal electroshock seizure was not affected by LC lesion, although the recovery time was slightly prolonged. In the pentylenetetrazol (PTZ) seizure threshold test, LC lesion significantly elevated the twitch threshold, but did not affect the threshold for the generalized clonic seizure or clonic convulsion. Incidence of the tonic extension in the PTZ seizure test tended toward an increase with LC lesion. Biochemical determinations revealed that LC lesion significantly decreased the norepinephrine contents in various brain regions as well as the 5-hydroxytryptamine contents of some brain regions, but not the 5-hydroxyindoleacetic acid contents. These results suggest that while the LC is involved in the regulation of seizure susceptibility, the involvement differs with various types of seizures.
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PMID:The role of the locus coeruleus in regulation of seizure susceptibility in rats. 618 32

Hindlimb extension (HLE) induced by maximal electroshock seizures (MES) can be markedly affected by drugs which affect CNS 5-hydroxytryptamine (5-HT). Consequently, it has been proposed that the natural resistance of certain rats (flexor rats) to HLE is due to elevated levels of 5-HT. We have tested the hypothesis that the increased resistance of flexor rats to MES-induced HLE is due to elevated serotonergic levels in some region(s) of the CNS by examining 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels in 8 regions of the CNS in rats classified by MES as either flexors or extensors. Furthermore, we compared the in vivo synthesis rate of 5-HT between flexor and extensor rats in 6 regions of the brain by measuring the accumulation of 5-HTP following aromatic amino acid decarboxylase inhibition with NSD-1015. All neurochemical analyses were carried out on rats sacrificed one week after their last seizure test. No differences in 5-HT, 5-HIAA or 5-HTP synthesis rate were detected between flexor and extensor rats for any of the regions examined, suggesting that enhanced serotonergic levels are not responsible for the unusual resistance of flexor rats to HLE.
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PMID:Comparison of regional brain 5-HT and 5-HIAA content in flexor and extensor rats. 619 44

In a pilot single-blind study, gamma-vinyl GABA, an enzyme-activated irreversible inhibitor of GABA-transaminase (GABA-T), was administered orally to 10 epileptic patients who were refractory to conventional anticonvulsant therapy. Daily doses of 1 g and 2 g for 2 weeks each as add-on therapy were followed by 2 weeks of placebo treatment. CSF obtained from suboccipital and lumbar punctures demonstrated dose-related increases in concentrations of free and total GABA and homocarnosine with treatment, but no changes in 5-hydroxyindoleacetic acid or homovanillic acid levels, indicating effective and selective CNS GABA-T inhibition. These biochemical changes were associated with decreased seizure frequency in seven patients, decreased seizure severity in one, no change in one, and possible worsening in one. gamma-Vinyl GABA may be useful in the therapy of epilepsy.
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PMID:Biochemical and clinical effects of gamma-vinyl GABA in patients with epilepsy. 653 6

The neurotoxic and convulsant properties of conformationally restricted and synthetic analogues of excitatory acidic amino acids were examined after stereotaxic injection into the striatum and the dentate gyrus of the hippocampal formation. In the striatum, neurotoxicity was quantified by the reduction in the activity of choline acetyltransferase and glutamate decarboxylase, markers for striatal intrinsic neurons. The following sequence of neurotoxic potencies was defined; kainic acid approximately equal to domoic acid much greater than alpha-keto kainic acid approximately equal to alpha-allo kainic acid greater than ibotenic acid approximately equal to cis-cyclopentyl glutamic acid greater than quisqualic acid approximately equal to N-methyl-D-aspartic acid. When normalized for neurotoxic potencies, a wide variation in the convulsant effects of the agents was observed after hippocampal injection. N-Methyl-D-aspartate produced nearly continuous electroencephalographic seizures for 2 hr after injection, where alpha-keto-kainate and kainate and quisqualate caused seizure activity for 64 and 45% respectively of this period; kainate, alpha-allo kainate and domoate caused intermittent seizure activity during approximately 30% of the recording period; ibotenate and cyclopentylglutamate had minimal convulsant effects. Seizures were associated with a significant reduction in the levels of norepinephrine and with increases in the levels of 5-hydroxyindoleacetic acid in the cortex and hippocampal formation and increases in the levels of gamma-aminobutyric acid in the hippocampal formation. Kainate, domoate, keto-kainate and alpha-allo-kainate caused extensive lesions of the hippocampal formation that also involved the pyriform cortex; ibotenate and cyclopentylglutamate caused uniform but substantial lesions limited to the dentate gyrus, whereas quisqualate and N-methyl-D-aspartate produced small and restricted lesions. The results demonstrate a poor correlation between the neurotoxic and convulsant potencies of these excitatory amino acid analogues and suggest that receptor-specific interactions may account for these disparities.
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PMID:Excitatory amino acid analogues: neurotoxicity and seizures. 706 5

Dihydroergotoxine administration shortened the latency of allylglycine-and picrotoxin-induced convulsions in rats and increased the incidence of convulsions elicited by picrotoxin, i.e., it lowered ED50 for picrotoxin. The same drug (0.1-10.0 mg/kg) decreased the levels of gamma-aminobutyric acid (GABA) in the caudate nucleus and cingulate cortex, but enhanced the aminooxyacetic acid induced accumulation of GABA indicating an increased synthesis of GABA in these brain regions. The concentrations of 5-hydroxytryptamine, 5-hydroxyindoleacetic acid, noradrenaline, and dopamine in the whole rate brain were not affected with doses of dihydroergotoxine up to 10.0 mg/kg, but this dose of the drug slowed down the turnover of dopamine, as evidenced by a diminished disappearance of dopamine induced by alpha-methyl-p-tyrosine administration. The results suggest that dihydroergotoxine decreases GABA-ergic transmission and, therefore, presumably lowers the seizure threshold.
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PMID:Dihydroergotoxine and the Seizure Threshold. 729 68

Serotonin(5-HT) plays an important role in the seizures of El mice since the seizure threshold of El mice correlates with the 5-HT concentration in the central nervous system. In this study, the anticonvulsant effect of a 5-HT reuptake blocker, citalopram, was evaluated behaviorally and biochemically. El mouse convulsions were inhibited by oral administration of citalopram for 2 weeks. Citalopram increased tryptophan and tyrosine amounts, and decreased the 5-HT, 5-hydroxyindoleacetic acid, kynurenine, and dopamine amounts in the brain. These findings show that citalopram depresses monoaminergic metabolism. Given the known convulsant effect of kynurenine, it is suggested that its decrease by citalopram may involve attenuation of El mice seizures.
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PMID:The anticonvulsant effect of citalopram on El mice, and the levels of tryptophan and tyrosine and their metabolites in the brain. 752 May 38

This study was designed to demonstrate a role of serotonin in the anticonvulsant effect of fluoxetine, a serotonin reuptake inhibitor, in genetically epilepsy-prone rats. When varied doses of 5-hydroxytryptophan (12.5, 25, 50 mg/kg) were administered i.p. along with a fixed dose of fluoxetine (15 mg/kg) to severe seizure genetically epilepsy-prone rats, the severity of audiogenic seizures was decreased dose-dependently, and the combination treatment also produced a marked potentiation of the anticonvulsant effect when compared with administration of either drug alone. Pretreatment of severe seizure genetically epilepsy-prone rats with p-chlorophenylalanine depleted brain serotonin and reduced the anticonvulsant effectiveness of fluoxetine. By using intracerebral microdialysis, the depletion of serotonin after p-chlorophenylalanine treatment was confirmed by measuring thalamic extracellular serotonin and 5-hydroxyindoleacetic acid concentrations during basal release and in response to a challenge dose of fluoxetine. We concluded that serotonergic transmission may be involved in the anticonvulsant effect of fluoxetine in severe seizure genetically epilepsy-prone rats.
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PMID:Role of serotonin in the anticonvulsant effect of fluoxetine in genetically epilepsy-prone rats. 752 1

To study the purported role of central monoamine disturbances in the pathophysiology of the opsoclonus-myoclonus syndrome, the serotonin metabolite 5-hydroxyindoleacetic acid and the dopamine metabolite homovanillic acid were measured in cerebrospinal fluid samples from 27 affected children and 47 age- and gender-matched control subjects by high-pressure liquid chromatography with electrochemical detection. 5-Hydroxyindoleacetic acid and homovanillic acid concentrations in the cerebrospinal fluid were approximately 30 to 40% lower in opsoclonus-myoclonus patients compared to control subjects, and the normal inverse correlation between age and monoamine metabolite concentrations in the cerebrospinal fluid of control subjects was not found in opsoclonus-myoclonus patients. Patients with the lowest values were less than 4 years old, and a subgroup had extremely low levels, but differences in older children were not significant. Cerebrospinal fluid levels of 5-hydroxyindoleacetic acid and homovanillic acid were more positively correlated in control subjects than in opsoclonus-myoclonus patients. None of the patients exhibited high levels of monoamine metabolites. Homovanillic acid levels were slightly lower in the cerebrospinal fluid of patients receiving corticotropin or steroids at the time of lumbar puncture. Clinical variables that could be excluded were paraneoplastic etiology, anesthetic for lumbar puncture, syndrome duration, age at onset, gender, response to steroids, length of time until initiation of corticotropin or steroids, presence of seizures, opsoclonus, and functional impairment. These data suggest a disturbance and possible altered ontogeny of serotonin or dopamine neurotransmission in a subpopulation of children with opsoclonus-myoclonus with low cerebrospinal fluid levels of 5-hydroxyindoleacetic acid and homovanillic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cerebrospinal fluid 5-hydroxyindoleacetic acid and homovanillic acid in the pediatric opsoclonus-myoclonus syndrome. 753 17


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