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

We determined the concentrations of manganese in whole blood and hair in 52 epileptics, 6 blood relatives, and 24 normal controls. Blood, and possibly hair manganese content, was significantly lower in treated epileptics than in controls (p less than 0.002). Although not all patients showed reduced tissue manganese levels, most of those with frequent seizures had manganese levels falling below the lowest control level, suggesting a relationship between manganese tissue levels and high seizure activity. These differences in manganese levels were not correlated with the type, dose, or plasma levels of anticonvulsant medication. Reduced manganese availability at the neuronal level, where Mn++ stabilizes membrane excitability, may affect epileptogenic lesions to increase the likelihood of seizure activity.
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PMID:Seizure disorders and trace metals: manganese tissue levels in treated epileptics. 57 99

The effects of the intraventricularly administered cations (Mn2+, Ca2+, Mg2+ and Li+) against the seizure induced by ouabain (3 microgram) were investigated. Mn2+, Ca2+ and Mg2+ caused definite sedation and decreased locomotor activity. But Li+ was without significant behavioral effect at the doses applied. Among the cations used, Mn2+, Ca2+ and Mg2+ showed significant anticonvulsive effect on the ouabain-induced seizure. In comparison, on the dose and molar-to-molar basis, the potency of anticonvulsive action was in the following order: Mn2+ greater than Ca2+ greater than Mg2+. On the contrary, the higher dose of Li+ potentiated the ouabain-induced seizure. The importance of the increased Ca2+ level in the extracellular space or the inhibition of Ca2+ uptake as the anticonvulsive effect of Ca2+, Mn2+ and Mg2+ was discussed.
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PMID:Effects of manganese, calcium, magnesium and lithium on the ouabain-induced seizure. 60 66

The observation in 14 dialysis patients of an encephalopathy associating myoclonia, dysarthria, generalised seizures in some cases, worsening over a few months, led to an aetiological inquiry based upon comparative study of patients with or without encephalopathy treated in the same centre or at home, and controls. Higher levels of aluminium were found in the frontal cortex grey matter of encephalopathy patients as compared to the control group. The same applies to manganese in the white matter. Copper, zinc and iron contents were not different. Aluminium levels in blood, dialysis bath and tap water supply were higher in center dialysis than in home dialysis. Blood aluminium levels at the end of hemodialysis were correlated with bath aluminium levels. The ingestion of alumine gels was not greater in the encephalopathy patients than in other hemodialysis patients; its estimation, in each case, was not related to the blood aluminium levels at the begining of hemodialysis. These finding indicate the need of a routine measure of metal content - mainly aluminium and manganese - in tap water used for dialysis, in order to treat this water if necessary.
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PMID:[Progressive myoclonic encephalopathy in dialysis patients. The role of the water used for haemodialysis (author's transl)]. 65 14

Since glutamine synthetase (GS) has been proposed as the primary enzyme in the regulation of glutamate metabolism in the central nervous system and since inhibition of the activity of this enzyme in vivo leads to seizures, it has been proposed that an abnormality in the structure or function of this enzyme could be responsible for the induction of seizures in epilepsy prone rats. To test this hypothesis the glutamine synthetases were purified from the brains of both genetically epilepsy prone rats (GEPR) and their progenitors, genetically epilepsy resistant rats (GERR). The enzymes were compared using both SDS-PAGE and isoelectric focusing. The immunoreactivities of equal amounts of protein were determined using the ELISA technique, and the regulation of the glutamine synthetase activities by Mn2+/Mg2+ ratios were compared. The only difference found between the glutamine synthetases from the two strains was a slightly lower specific activity of the enzyme from the epilepsy prone animals.
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PMID:Comparison of glutamine synthetases from brains of genetically epilepsy prone and genetically epilepsy resistant rats. 135 42

This study investigated the actions of proline on CA1 hippocampal pyramidal cells with use of slice preparations. Bath-applied L-proline first induced these cells to fire multiple orthodromic population spikes in response to a single stimulus and then blocked their response to both orthodromic and antidromic stimulation. These effects could be explained by postsynaptic depolarization followed by depolarization block. Grease-gap studies confirmed that L-proline depolarizes CA1 pyramidal cells. D-Proline was inactive in these tests. Excitatory amino acid antagonists reduced depolarizing responses to proline and N-methyl-D-aspartate (NMDA) in parallel. Mn2+ failed to attenuate proline-evoked depolarizations at concentrations that substantially inhibited synaptic transmission, but at a higher concentration it reduced responses to both proline and NMDA. These results suggest that proline depolarized CA1 pyramidal cells mainly by activating postsynaptic NMDA receptors. The neuroexcitatory and neurotoxic actions of proline in the hippocampus may contribute to the seizures and mental retardation associated with hyperprolinemia.
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PMID:NMDA receptor-mediated depolarizing action of proline on CA1 pyramidal cells. 135 8

Since trace element abnormalities have been found in the human epileptic population, trace element concentrations were determined in blood and tissues of genetically epilepsy-prone rats both exposed to an unexposed to seizure-inducing stimuli and in genetically related epilepsy-resistant rats. Half of the epilepsy-prone group were exposed to seizure-inducing sound twice daily for 3 weeks. Food intake and weight gain were monitored for each animal. Genetically epilepsy prone rats with induced seizures consumed significantly less food and gained less weight than did the epilepsy resistant group. Seizure prone rats without seizures consumed the same amount of food as the resistant rats but gained less weight than the resistant strain but more than the seizure-induced animals. Epilepsy-prone animals had significantly altered trace element concentrations in tissues as compared with the resistant animals independent of seizure induction. Brain and liver iron, liver copper, and brain and heart manganese levels were all significantly lower in the seizure-prone rats as compared with the seizure-resistant rats. In the seizure-prone rats, induction of seizures resulted in an increase in brain and heart zinc levels and a decrease in whole blood manganese levels. These results demonstrate that both genetic factors relevant to susceptibility to seizures and the seizures themselves are associated with changes in trace element concentrations.
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PMID:Genetically epilepsy-prone rats are characterized by altered tissue trace element concentrations. 234 41

It has been shown that epileptics have lower mean blood concentration of manganese than do controls but the cause of this abnormality has not been determined. In order to investigate the effects of seizures on manganese distribution in the body, rats were treated with kainic acid to produce spontaneous seizures which were quantitated for number and severity. Manganese, zinc, copper and iron concentrations were determined in blood, brain, liver, heart and kidney. Kainate-treated animals ate more food but gained less weight than controls. Liver and kidney manganese concentrations were significantly higher in kainate-treated animals than in controls. Blood manganese concentration showed a significant negative correlation with seizure index while heart manganese concentration showed a significant positive correlation with seizure index. None of the other trace elements showed a significant correlation between trace element concentration and seizure index in any of the tissues, although iron concentration was lower in brain and copper concentration was lower in kidney of kainate-treated animals than in their appropriate controls. These data show that manganese concentrations are generally elevated in tissues of kainate-treated animals. This increased manganese concentration may be related to the increased energy demand of these animals.
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PMID:Effect of kainate-induced seizures on tissue trace element concentrations in the rat. 260 57

1. Neocortical slices of the first and second temporal gyrus and frontal lobe, removed in human epileptic patients for the relief of intractable seizures, were maintained in vitro at 35 +/- 1 degrees C. Electrophysiological properties of neurons in the deep layers (1,800-2,600 micron below the pial surface) were studied with conventional intracellular recording and stimulation techniques. Synaptic responses were evoked by extracellular focal stimuli. Intracellular injections of some cells with the fluorescent dye Lucifer yellow revealed large spiny pyramidal neurons. 2. Values of input resistance, resting membrane potential (Vm), and action-potential amplitude were similar for neurons in different cortical regions. These parameters were also similar when neurons were grouped in accordance to the degree of electrographic epileptiform activity displayed by the cortical tissue in situ. 3. Inward rectification occurred when neurons were depolarized by 5-15 mV positive to the resting Vm. This rectification was abolished by extracellular application of tetrodotoxin (TTX, 1 microM), but was still observed in the presence of the Ca2+-channel blocker Cd2+ (2 mM). Pulses of hyperpolarizing current elicited a slowly developing inward rectification, called anomalous rectification, which was insensitive to TTX, but blocked by extracellular application of Cs+ (1-2 mM). 4. Intracellular injection of depolarizing square pulses of current (0.1-4 s) evoked repetitive firing. In most cells the firing rate decreased smoothly for tens of milliseconds (i.e., it adapted) before reaching a steady level. Plots of the relation between frequency of the repetitive firing and injected current (f-I curve) displayed two linear segments for the early intervals as well as for the adapted and/or the steady firing. The slope of the initial, steeper linear segment of the f-I curve computed during the early intervals and during the adapted firing was 163 +/- 51 and 56 +/- 27 (SD) Hz/nA, respectively. 5. A long-lasting (up to 8 s) afterhyperpolarization (AHP) followed the repetitive firing induced by square pulses of depolarizing current. Its amplitude was directly proportional to the amount of current injected, it was sensitive to changes in the Vm, and it had an equilibrium potential 10-40 mV negative to the resting Vm. This value plus the fact that the AHP could be recorded with KCl-filled microelectrodes suggested that it was caused by an increase in conductance to K+ ions. Bath application of the Ca2+ channel blockers Cd2+ (2 mM) or Mn2+ (2 mM) decreased and eventually blocked the AHP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Electrophysiological properties and synaptic responses in the deep layers of the human epileptogenic neocortex in vitro. 270 2

Zinc ions, which are unevenly distributed in the CNS and can be released from nerve terminals, have been implicated as causative agents in epileptogenesis. The present study has shown that intraventricular administration to anesthetized rats causes seizure activity of the ECOG and convulsions. Since the manner in which zinc influences neuronal activity and triggers convulsions is unclear, studies were also made of its effect on spontaneous and evoked activity in the rat forebrain. It was found that iontophoretic application of zinc to cortical neurons causes slow and often prolonged increases in firing rate, usually accompanied by bursts of high frequency discharge in just under half the studies. Another cation, barium, evoked excitatory responses of a similar type and a reduction in potassium permeability may underlie the effects of both cations. In contrast, calcium, magnesium, manganese and cerium caused short duration depressant effects. The depression induced by calcium, but not by the other cations, could be blocked by zinc. Similarly, in the hippocampus zinc depressed calcium-dependent potentiation in subfield CA3 evoked by paired-pulse stimulation of mossy fibers; excitatory effects (namely an increase in spike amplitude and appearance of multiple population spikes) were seen at higher zinc concentrations. The depressant effects of an enkephalin analog on cortical firing rate were also blocked by zinc, consistent with studies from another laboratory suggesting enkephalin/zinc interactions. In contrast, the depressant effect of GABA could not be blocked by zinc, although an antagonism has been reported in the lobster muscle. Firm conclusions regarding the mechanism(s) underlying the triggering of seizure activity by zinc cannot yet be drawn, but the results of these studies would be consistent with an interference with calcium and/or potassium ion activity rather than with GABA binding sites.
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PMID:Effect of zinc on neuronal activity in the rat forebrain. 302 63

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese-containing compound which is used as an additive in unleaded gasoline. One neurotoxic effect of MMT in mice is seizure activity. In this study, seizures were observed in mice treated with MMT in propylene glycol or corn oil. The LD50 associated with seizure activity was lower in mice receiving MMT in propylene glycol (152 mg/kg) than in those receiving MMT in corn oil (999 mg/kg). Manganese concentrations in the brains of mice which showed seizure activity due to MMT were higher than in those that did not (2.45 micrograms/g vs. 1.14 micrograms/g for MMT treated in propylene glycol and 3.25 micrograms/g vs. 1.63 micrograms/g for MMT in corn oil). Mice treated with manganese chloride (MnCl2) showed increases in brain manganese comparable to those of the mice showing seizure activity due to MMT, but exhibited no sign of seizure activity. MMT in non-lethal seizure-inducing doses had no effect on the accumulation of 4-aminobutyric acid (GABA) in mouse brain. However, MMT inhibited the binding of t-[3H]t-butylbicycloorthobenzoate [3H]-TBOB (a ligand for the GABA-A-receptor linked chloride channel) in mouse brain membranes with an IC50 value of 22.8 microM. The data suggest that MMT (organic manganese) or a closely related metabolite and not elemental manganese itself is responsible for the seizure activity observed. The seizure activity may be the result of an inhibitory effect of MMT at the GABA-A receptor linked chloride channel.
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PMID:Neurotoxic effects of methylcyclopentadienyl manganese tricarbonyl (MMT) in the mouse: basis of MMT-induced seizure activity. 360 84


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