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

Bilateral lesions involving the nucleus locus coeruleus produced a substantial decrease in the forebrain noradrenaline concentrations. Lesioned animals showed an increased susceptibility to audiogenic seizures. It is supposed that noradrenergic neurons, belonging to the locus coeruleus, play an inhibitory role in the seizure mechanism.
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PMID:Audiogenic seizures in rats: relation to noradrenergic neurons of the locus coeruleus. 74 2

Mice with a genetically determined susceptibility to audiogenic seizures were utilized to analyze the ontogeny of central monoamine neurotransmission in relation to a behavior with age-specific properties. Levels of noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) were measured in forebrain and hindbrain regions at 14, 21, 28, and 42 days postnatal age in genetically sensitive or resistant strains of mice. An in vivo estimate of tyrosine and tryptophan hydroxylase activity was obtained at the same ages by following the accumulation of 3,4-dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) respectively, after the administration of a centrally effective L-amino acid decarboxylase inhibitor (R04-4602, 800 mg/kg). At 14 days, there was a faster rate of accumulation of DOPA in both the forebrain and hindbrain of the sensitive mice compared to mice of the nonsensitive strain. At 21 days, the age of maximal sensitivity in the sensitive mice, the levels of NA were significantly lower in both regions of the sensitive mice, but the accumulation of DOPA was similar between strains at this age. There was also a slightly lower level of 5-HT in the forebrain of sensitive mice at 21 days accompanied by a slower rate of accumulation of 5-HTP in this region. In the hindbrain of the sensitive animals however, the rate of accumulation of 5-HTP was faster than in the sensitive strain. At 28 days, some impairment in mechanisms within NA-containing neurons in the sensitive mice was still apparent (including lower NA levels). At 42 days, there were no differences in amine levels, however, the levels of accumulated DOPA and 5-HTP were significantly lower in the sensitive strain. The results suggest that in the sensitive mice, developmental differences in mechanisms of monoamine storage and/or synthesis may exist which could contribute to deficient amounts of physiologically releaseable transmitter.
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PMID:Audiogenic seizures: relation to age and mechanisms of monoamine neurotransmission. 108 62

In this review, the main characteristics of genetic models of absence epilepsy, in particular with respect to WAG/Rij rats, are presented. Genetic models are important and relevant, since evidence exists that these models mimic spontaneously occurring human epilepsy more than models in which epilepsy is artificially induced. Genetic models can be divided into models in which seizures are elicited and into those in which epilepsy appears without any sensory stimulation. The majority of genetic models show that absence type of epilepsy; during the last few years, we and others have noticed that rats of various strains exhibit spontaneously occurring spike-wave discharges in the EEG. Among the strains highly affected is the WAG/Rij strain, which is a fully inbred strain. Individuals are homozygous and because of this property, genetic studies are meaningful. Electrophysiological studies have indicated that abnormal discharges in the cortical EEG are generalized and that the hippocampus is not involved. Parts of the thalamus, together with the thalamic reticular nucleus, apparently act as a pacemaker for the abnormal discharges. There is a circadian modulation in the number of spike-wave discharges. Discharges mainly occur during intermediate levels of vigilance such as passive wakefulness and light slow-wave sleep and at transitions of sleep states. Pharmacological studies with clinically effective antiepileptic drugs have shown a close agreement in seizure response between man and rat. Studies with new compounds have emphasized the role of the GABAergic and glutamatergic system in this type of epilepsy. Particularly striking is the role of the GABAergic system. GABA agonists enhance and GABA antagonists reduce the occurrence of spike-wave discharges, which deviates from the effects of GABAergic drugs in non-convulsive epilepsy. Even more striking is the role of the benzodiazepines, generally seen as GABA agonists; these drugs do not act as such in absence epilepsy since they reduce spike-wave discharges. Also good evidence for an involvement of other neurotransmitters such as noradrenaline, dopamine and opioid peptides exists in absence epilepsy. Genetic data obtained from the WAG/Rij model for absence epilepsy show a relatively simple pattern of inheritance with one gene determining whether an individual is epileptic or not, and with other genes regulating the number and duration of seizures. This is in good agreement with the more restricted human data. Cognitive studies have shown two important features of epilepsy in the WAG/Rij strain: modulation of the number of spike-wave discharges by mental or physical activity and on the other hand, the disruption of cognitive activity by spike-wave discharges.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Genetic models of absence epilepsy, with emphasis on the WAG/Rij strain of rats. 139 43

Fourteen male Wistar rats were divided into two groups. The experimental rats were injected with subconvulsive dosage of coriaria lactone (1 mg/kg) intramuscularly per 3.5 days. The controls were injected with normal saline. After 26 injections, the loci coeruleus of kindling rats were studied with the noradrenaline (NA) fluorescence histochemical technique at the time between seizures. The NA fluorescence could be clearly visualized under fluorescent microscope. The intensity of fluorescence was reflected by autoexposure-meter of the fluorescent microscope. The brighter the fluorescence, the shorter the autoexposure time. The intensity of NA fluorescence in the locus coeruleus of experimental animals was weaker than that of the controls. Since NA plays an inhibitory role in cerebral cortex, the decrease of NA, either induced by repeated injections of coriaria lactone or due to the time of sample taken after seizure, needs further study.
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PMID:[Noradrenaline fluorescence histochemical study on the locus coeruleus of kindling rat induced by coriaria lactone]. 145 43

Twenty-four adult male Wistar rats were used in this study. Status epilepticus was provoked in 10 rats by embedding coriaria lactone particle into the left cerebral motor cortex. In the controls were embedded particles without coriaria lactone. After 6 h of continuous seizure, the locus coeruleus was studied with the noradrenaline (NA) fluorescence histochemical technique and enzyme histochemical test for monoamine oxidase (MAO). The intensity of NA fluorescence was detected with fluorescent microscope autoexposuremeter and analysed with MIAS-200 Image Analyser. The study group showed a parallel increase of NA fluorescence as compared with that of the control group by both measurements. NA plays an inhibitory role in the cortex. Our data suggest that the increase of NA in locus coeruleus may be due to the reduction of NA release from axon terminal. Reduction in inhibition could be one of the mechanisms of seizure activity. The intensity of MAO was detected with MIAS-200 Image Analyser. The regulation of monoamine metabolism by MAO in the central nervous system and the increase of MAO activity in the continuous seizure group may be induced by the accumulation of NA in the locus coeruleus soma.
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PMID:[Histochemical and image-analytic study of the rat locus coeruleus during status epilepticus]. 145 44

The selective serotonin reuptake inhibitors (SSRIs) are a tribute to the ingenuity of pharmacologists and designers of molecules. Not only do these drugs have remarkable selectivity for the reuptake of serotonin compared with other monoamines, but also they have a commendable lack of affinity for receptors including the serotonin receptor. In contrast, the classical tricyclic antidepressants (TCAs) are less specific in their pharmacological action. In addition to inhibiting the reuptake of serotonin, TCAs inhibit the uptake of noradrenaline, dopamine and tyramine, and antagonize cholinergic (muscarinic), adrenergic and histaminergic receptors. Moreover, TCAs have quinidine-like anti-arrhythmic activity and lower the seizure threshold. Clinical investigations have shown that the SSRIs have equivalent therapeutic efficacy compared with the TCAs in the treatment of depression. However, the pharmacological specificity of the SSRIs is a clinical advantage since they lack the propensity to cause dry mouth, blurred vision, urinary hesitancy, constipation, hypotension and arrhythmia. Furthermore, the SSRIs are relatively safe in overdosage. The similarities between the SSRIs are more obvious than their differences: all are highly potent and selective inhibitors of serotonin reuptake with efficacy in the treatment of depression. Nevertheless, each has a distinctive pharmacological profile. In this review the characteristics desired in an "ideal" antidepressant are examined, and the ways in which the TCAs and SSRIs fit this ideal are compared.
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PMID:Clinical implications of the pharmacology of serotonin reuptake inhibitors. 148 74

The radioautographic analysis of [3H]clonidine binding was performed on brain slices from the convulsive mutant mice quaking and their controls of the same strain. In the quaking mice significant increases were observed mostly in the brainstem and the cerebellum, but also in a few regions of the forebrain, such as the lateral and medial thalamic nuclei, the medial geniculate nucleus, the amygdala and the hypothalamus. Other regions, such as the cerebral cortex and the hippocampus, which are classically involved in various models of epilepsy, but not in the quaking mice, did not show any modification of [3H]clonidine binding. A high degree of correlation was found between the structures with an increased density of alpha 2-adrenoceptor binding sites and the distribution of regions from which seizures can be elicited by intracerebral electrical stimulation in head-restrained quaking mice. This comparison emphasizes the role of noradrenaline acting at the level of alpha 2-adrenoceptors in the epileptic syndrome of the quaking mutants.
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PMID:Distribution of [3H]clonidine binding sites in the brain of the convulsive mutant quaking mouse: a radioautographic analysis. 151 Dec 79

We have selected a strain of rats and designated it the Genetic Absence Epilepsy Rat from Strasbourg (GAERS). In this strain, 100% of the animals present recurrent generalized non-convulsive seizures characterized by bilateral and synchronous spike-and-wave discharges accompanied with behavioural arrest, staring and sometimes twitching of the vibrissae. Spontaneous SWD (7-11 cps, 300-1,000 microV, 0.5-75 sec) start and end abruptly on a normal background EEG. They usually occur at a mean frequency of 1.5 per min when the animals are in a state of quiet wakefulness. Drugs effective against absence seizures in humans (ethosuccimide, trimethadione, valproate, benzodiazepines) suppress the SWD dose-dependently, whereas drugs specific for convulsive or focal seizures (carbamazepine, phenytoin) are ineffective. SWD are increased by epileptogenic drugs inducing petit mal-like seizures, such as pentylenetetrazol, gamma-hydroxybutyrate, THIP and penicillin. Depth EEG recordings and lesion experiments show that SWD in GAERs depend on cortical and thalamic structures with a possible rhythmic triggering by the lateral thalamus. Most neurotransmitters are involved in the control of SWD (dopamine, noradrenaline, NMDA, acetylcholine), but GABA and gamma-hydroxybutyrate (GHB) seem to play a critical role. SWD are genetically determined with an autosomal dominant inheritance. The variable expression of SWD in offsprings from GAERS x control reciprocal crosses may be due to the existence of multiple genes. Neurophysiological, behavioural, pharmacological and genetic studies demonstrate that spontaneous SWD in GAERS fulfill all the requirements for an experimental model of absence epilepsy. As the mechanisms underlying absence epilepsy in humans are still unknown, the analysis of the genetic thalamocortical dysfunction in GAERS may be fruitful in investigations of the pathogenesis of generalized non-convulsive seizures.
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PMID:Genetic absence epilepsy in rats from Strasbourg--a review. 151 94

Delirium tremens is linked with a chronic depression of the central nervous system by alcohol and a compensatory hyperactivity of neurotransmitters. A sudden stoppage of alcohol intake induces excessive production of these transmitters. Firstly appearing is a noradrenergic hyperactivity which may be responsible not only for reducing the magnesium blood level but also for activating the other transmitter systems. A magnesium blood level lower than 1 mmol.l-1 involves a risk of seizures and requires IV magnesium sulfate. Noradrenergic hyperactivity can be prevented by IV alcohol associated with sedation best achieved by IV clomethiazole in alcoholic solution. Should these preventive measures fail, noradrenaline action in the central nervous system can be blocked by clonidine. Should hallucinations become manifest, linked to dopaminergic hyperactivity, haloperidol is indicated. Benzodiazepines may be useful, particularly carbamazepine, for their depressing effect on gaba-ergic hyperactivity.
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PMID:[Delirium tremens. Recent neurophysiologic concepts and therapeutic outlook]. 151 60

The effects of selective and specific alpha 2-adrenoceptor antagonists on electroshock seizure threshold in mice were investigated. Idazoxan, at low doses, efaroxan, RX811059 and RX821002 significantly lowered seizure threshold. The alpha 1-agonist St 587 and the beta-agonist isoprenaline were also pro-convulsant. On the other hand the alpha 2-agonists clonidine and UK 14,304 produced small increases in seizure threshold. Anticonvulsant effects were also produced by low doses of the noradrenaline uptake inhibitor desipramine. This compound increases levels of noradrenaline in the synaptic cleft which could subsequently act at post-synaptic alpha 2-adrenoceptors. The pro-convulsant action of alpha 2-adrenoceptor antagonists could be explained in terms of two mechanisms: a) blockade of endogenous noradrenaline which may normally exert a tonic anti-convulsant influence on seizure threshold, through post-synaptic alpha 2-receptors and/or b) increased activation of alpha 1- and beta-adrenoceptors by elevated synaptic noradrenaline levels following blockade of pre-synaptic alpha 2-adrenoceptors. Of the alpha 2-antagonists tested, idazoxan was unusual in that high doses were not pro-convulsant; this difference may be explained by alpha 1-adrenoceptor mediated actions or be related to its recently described affinity at a non-adrenoceptor site--a function for which is currently unknown.
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PMID:Exploring the pharmacology of the pro-convulsant effects of alpha 2-adrenoceptor antagonists in mice. 168 54


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