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

Guanidino compounds are known to have important biological roles, such as the participation of arginine in ureagenesis, and of creatine in muscular contraction. On the other hand, the high toxicity of guanidino compounds, such as methylguanidine and guanidine, has been under study for quite a long time in the biochemical as well as clinical fields. In this review, the author summarizes the experimental results of neurophysiological and neurochemical studies on guanidino compound-induced seizures, conducted by his colleagues since 1966, and introduces several topics arising from their recent investigations on guanidino compounds and seizure mechanism, i.e., (1) alpha-guanidino-glutaric acid in the cobalt epileptic focus and its convulsive activity; (2) guanidino-ethanesulfonic acid and epilepsy; (3) delta-guanidinovaleric acid, and endogenous and specific GABA receptor antagonist; and (4) guanidino compounds as radical generators.
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PMID:Biochemistry and neurotoxicology of guanidino compounds. History and recent advances. 282 70

The seizure state induced in the rat by cerebral cortical implantation of cobalt metal has been increasingly used to study a variety of neurochemical parameters. This experimental model of epilepsy affords the opportunity to study events prior to the development of seizures, during the period of intense seizure activity, and during the period when seizure activity has essentially terminated. The seizures that occur in this model are intermittent and paroxysmal and share many other similarities with human epilepsy. The crucial question with this model, and indeed with any experimental model of epilepsy, is whether the basic seizure-producing mechanism(s) is similar. This question remains to be answered. There have been studies that show that changes in certain neurochemical parameters parallel the onset, intensity, and decline of seizure activity in cobalt-epileptic animals. Although extremely interesting, by themselves they do not prove a cause-and-effect relationship. Such parallelism is more apparent in the case of GABA than in the cases of lipids and gangliosides. GABA and its synthetic enzyme, glutamic acid decarboxylase (GAD), are both at normal levels prior to the development of seizures, are significantly decreased during the period of seizures, and return toward control values at a time when seizures are no longer apparent. On the other hand, there is no change in postsynaptic GABA binding sites (Bmax) prior to seizures, a significant increase in Bmax during seizure activity, and a return toward normal by 21 days (when seizure activity has terminated). Studies that have been carried out on lipids and gangliosides in cobalt-induced epilepsy are not nearly as extensive nor are the results as positive as those that have been obtained in the case of GABA. They do, however, provide provocative findings that may well be related to the genesis of epilepsy.
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PMID:GABA receptors, lipids, and gangliosides in cobalt epileptic focus. 301 Jun 78

This chapter reviews results which show that in electroshock-induced and chemically induced convulsions, audiogenic seizures of genetic epilepsy-prone rats and mice, in the kindling focus and the cobalt lesion seizure, susceptibility is modulated by a noradrenergic mechanism. In general, mechanisms that increase or decrease norepinephrine activities decrease or increase seizures, respectively, in these models. In the kindling phenomenon, since the seizure itself provokes an increase in norepinephrine (NE) turnover, with decreased beta-adrenoceptor binding and hyposensitivity to ionophoretic catecholamine application, down regulation could be the cause of hyperexcitability or a consequence of it. In the cobalt focus, supersensitivity to NE appeared when NE-containing terminal density decreased (denervation supersensitivity) and beta-receptor sites increased greater than 50%. Perfusion experiments with NE support the hypothesis that the cortical NE system inhibits the spread of chronic epileptogenic activities in the cobalt focus. In the quaking mouse and in the tottering mouse, noradrenergic dysfunction underlying epileptogenesis may be expressed as a hyperinnervation.
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PMID:Role of noradrenergic ascending system in extinction of epileptic phenomena. 301 Jun 81

To determine precisely how pentylenetetrazole (PTZ) is involved in the biochemical processes at the presynaptic nerve terminal, the effect of PTZ, under various conditions, on the phosphorylation of synapsin I (previously called protein I) was investigated, using 32Pi in synaptosomes from rat cerebral cortex. PTZ markedly stimulated the incorporation of 32P into this protein as determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and autoradiography, but it failed to stimulate protein phosphorylation in Ca2+-free medium containing ethylene glycol bis-(beta-aminoethylether)-N',N'-tetraacetic acid (EGTA). Moreover, the PTZ-stimulated synapsin I phosphorylation was reversed by addition of EGTA sufficient to chelate all external free Ca2+. PTZ also stimulated synaptosomal accumulation of Ca2+. The PTZ-stimulatory effects of both synapsin I phosphorylation and synaptosomal accumulation of Ca2+ were inhibited markedly by tetrodotoxin as well as by cobalt chloride and lanthanum chloride. The calmodulin antagonists N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7, strongly) and N-(6-aminohexyl)-1-naphthalenesulfonamide (W-5, weakly) reduced the PTZ-stimulatory effect on synapsin I phosphorylation by about 75 and 15%, respectively, whereas these antagonists had essentially no effect on PTZ-stimulated synaptosomal accumulation of Ca2+. These results suggest that PTZ causes the influx of Ca2+ into the presynaptic nerve terminal secondary to the elevated Na+ and is consequently involved in the synapsin I phosphorylation step, facilitating the Ca2+/calmodulin-mediated presynaptic event leading to seizure discharge.
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PMID:Involvement of pentylenetetrazole in synapsin I phosphorylation associated with calcium influx in synaptosomes from rat cerebral cortex. 310 72

The relationship between the focus of cobalt seizures in the cerebral cortex and neuron loss in the hippocampus, as well as the CD50 of pentylenetetrazol was examined in rats. Spike activity in EEG frequently appeared 4 days after cobalt application and reached a peak 8-16 days after cobalt application, which was sometimes accompanied by jerks in the limbs. Changes in the CD50 value showed a two-step pattern, i.e., the first decrease in CD50 appeared one day after application of cobalt and continued at the same value until the fourth day. Then a second gradual decrease of CD50 was observed from the fourth day to eighth day and continued at the same value until 20 days after cobalt application. Neuron loss in the CA1 area of the hippocampus was observed as early as two days after cobalt application and the degree of neuron loss progressively increased until the 20th day. These findings suggest that neuron loss in the hippocampus following cobalt-induced seizures is not a result of generalized convulsions.
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PMID:Damage of hippocampal neurons caused by cobalt focus in the cerebral cortex of rats. 316 81

Secondarily generalized convulsive status epilepticus was induced by intraperitoneal (i.p.) injection of D,L-homocysteine thiolactone to rats with actively epileptogenic cobalt lesions in motor cortex. This induced focal motor seizures which secondarily generalized. Control animals not treated with antiepileptic drugs had a mean of 18.3 generalized convulsions over a mean period of 103.8 min. Electrographic patterns seen during status epilepticus are described and are very similar to those seen during human status epilepticus. Phenytoin, phenobarbital, diazepam and lorazepam were all effective in arresting the generalized seizures when given i.p. after the second such seizure. Efficacy was serum drug concentration dependent. Concentrations effective in arrest of generalized seizures in this model are similar to those reported to be effective in the treatment of human status epilepticus. Diazepam ED50s for control of generalized tonic-clonic seizures and for arrest of all seizure activity were determined.
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PMID:Experimental secondarily generalized convulsive status epilepticus induced by D,L-homocysteine thiolactone. 319 90

Repetitive electrical stimulation and application of excitatory amino acids lead to decreases in extracellular Ca2+ concentration and to rises in extracellular K+ concentration [( Ca2+]o, [K+]o) with a typical laminar distribution in a given neo- or allocortical structure. These ionic changes result from transmembrane ion fluxes along their respective electrochemical gradients. Epileptogenic drugs that impair repolarizing K+ conductances or inhibitory synaptic transmission enhance such extracellular ionic changes, but they do not alter the laminar distribution of [K+]o and [Ca2+]o changes. Enhanced [Ca2+]o concentration changes are also observed in chronic epilepsies such as the chronic alumina cream and cobalt focus, the kindling epilepsy, and during photically induced seizures in the baboon Papio papio. In chronic epilepsies, the sites of maximal [Ca2+]o changes shift to other layers, suggesting changes in the distribution of ion channels over the surface of nerve cells that may be involved in epileptogenesis in chronic epilepsies. The K+ and Ca2+ concentration changes associated with seizure contribute to the generation and spread of epileptic activity. This is demonstrated by the fact that lowering of extracellular free calcium concentration can induce spreading epileptiform activity in the absence of chemical synaptic transmission, with [K+]o rises preceding epileptiform activity.
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PMID:Extracellular calcium and potassium concentration changes in chronic epileptic brain tissue. 351 50

The patient was a 24-year-old male who was admitted to the Dept. of Neurosurgery of Miyazaki Medical College in April of 1982 with a history of generalized convulsive seizures. Neurological examination on admission revealed slight mental disturbance, bilateral marked papilloedema and homonymous right upper quadrantanopsia. Plain skull X-ray films showed a destructive change of the bone in the left sphenoid ridge and sella floor. CT scan showed a huge mass of slightly high density in the left anterior and middle fossae with a marked enhancement with contrast media. It was fed mainly by the left anterior and middle cerebral arteries and partly by the left middle meningeal artery on angiogram. The tumor was considered to be a type of malignant meningioma originating from the left sphenoid ridge. Total removal of the tumor without any morbidity was thought to be difficult because of its size, hypervascularity and location. From clinical and radiological features, this tumor was thought to be an angioblastic meningioma of hemangiopericytoma type and to be radiosensitive. Cobalt-60 irradiation to the tumor was attempted with a total dose of 49 Gy for over a period of 6 weeks. CT scan performed at the stage of 23 Gy-irradiation showed high radiosensitivity of the tumor and CT scan two weeks after the completion of irradiation showed a marked reduction of its volume to one third. The patient became free from headache and memory disturbance after radiotherapy. On the forty eighth day after completion of the irradiation, the tumor was totally removed with ease and minimal bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Radiosensitive meningioma--report of a case]. 370 50

alpha-Guanidinoglutaric acid (alpha-GGA) was first found in cobalt-induced epileptogenic focus tissue in the cerebral cortex of cats. We examined the effect of alpha-GGA on the electroencephalogram and on the brain 5-hydroxytryptamine (5-HT) level after intraventricular administration into rats. Sporadic low-voltage spikes appeared 4 min after the administration of alpha-GGA. Spikes increased in voltage 6 min after the administration. Multiple spikes appeared 10 min after the administration, and they reached maximal frequency 30 min after the administration. The epileptic discharges disappeared 100 min after the administration. The 5-HT level increased in the right and left cortices 3 min after the administration. The 5-HT level decreased in the mid-brain 5 min after the administration and subsequently in all regions of the brain 10 min after the administration. No change in the 5-HT level was found 30 min and 100 min after the administration. These results show that alpha-GGA induces epileptic seizures in rats after intraventricular administration. The results also suggest that alpha-GGA-induced seizures are associated with abnormal serotonergic function and that they are initiated by a decrease in the 5-HT level.
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PMID:Convulsive activity of alpha-guanidinoglutaric acid and the possible involvement of 5-hydroxytryptamine in the alpha-guanidinoglutaric acid-induced seizure mechanism. 377 79

Several studies indicate that brain noradrenaline (NA) depletion facilitates the occurrence of epileptogenic syndromes in various animal models. In cobalt-induced epilepsy in the rat activity is associated with a cortical NA denervation. In order to search for cortical adrenoceptor modifications, inonophoretic studies and adrenoceptor binding assays were performed. At the period of maximal seizure activity, there was a significant supersensitivity of cortical neurons to the ionophoretic application of NA. An increase in the density of beta-adrenoceptor binding sites was observed. No modification in alpha 1- and alpha 2-adrenoceptor binding sites was found. This suggests that in cobalt-induced epilepsy there is a denervation supersensitivity which rests on a selective involvement of beta-adrenoceptors.
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PMID:Chronic cobalt-induced epilepsy: noradrenaline ionophoresis and adrenoceptor binding studies in the rat cerebral cortex. 390 Feb 90


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