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

Vitamins contain reactive functional groups necessary to their established roles as coenzymes and reducing agents. Their reactive potential may produce injury if vitamin concentration, distribution, or metabolism is altered. However, identification of vitamin toxicity has been difficult. The only well-established human vitamin neurotoxic effects are those due to hypervitaminosis A (pseudotumor cerebri) and pyridoxine (sensory neuropathy). In each case, the neurological effects of vitamin deficiency and vitamin excess are similar. Closely related to the neurological symptoms of hypervitaminosis A are symptoms including headache, pseudotumor cerebri, and embryotoxic effects reported in patients given vitamin A analogs or retinoids. Most tissues contain retinoic acid (RA) and vitamin D receptors, members of a steroid receptor superfamily known to regulate development and gene expression. Vitamin D3 effects on central nervous system (CNS) gene expression are predictable, in addition to the indirect effects owing to its influence on calcium and phosphorus homeostasis. Folates and thiamine cause seizures and excitation when administered in high dosage directly into the brain or cerebrospinal fluid (CSF) of experimental animals but have rarely been reported to cause human neurotoxicity, although fatal reactions to i.v. thiamine are well known. Ascorbic acid influences CNS function after peripheral administration and influences brain cell differentiation and 2-deoxyglucose accumulation by cultured glial cells. Biotin influences gene expression in animals that are not vitamin-deficient and alters astrocyte glucose utilization. The multiple enzymes and binding proteins involved in regeneration of retinal vitamin A illustrate the complexity of vitamin processing in the body. Vitamin A toxicity is also a good general model of vitamin neurotoxicity, because it shows the importance of the ratio of vitamin and vitamin-binding proteins in producing vitamin toxicity and of CNS permeability barriers. Because vitamin A and analogs enter the CNS better than most vitamins, and because retinoids have many effects on enzyme activity and gene expression, Vitamin A neurotoxicity is more likely than that of most, perhaps all other vitamins. Megadose vitamin therapy may cause injury that is confused with disease symptoms. High vitamin intake is more hazardous to peripheral organs than to the nervous system, because CNS vitamin entry is restricted. Vitamin administration into the brain or CSF, recommended in certain disease states, is hazardous and best avoided. The lack of controlled trials prevents us from defining the lowest human neurotoxic dose of any vitamin. Large differences in individual susceptibility to vitamin neurotoxicity probably exist, and ordinary vitamin doses may harm occasional patients with genetic disorders.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Vitamin neurotoxicity. 146 88

Effects of loreclezole (R72063), a triazole derivative with anticonvulsant properties, were studied on field potentials in rat hippocampal slices and on different patterns of low Mg(2+)-induced epileptiform activity in combined entorhinal cortex-hippocampal slices. Lowering extracellular Mg2+ induced recurrent (10-60/min), short (40-80 ms) discharges in hippocampal areas CA1 and CA3. In the entorhinal cortex (EC) up to 90 s long ictaform events associated with large negative field potential and changes in the neuronal microenvironment were generated. These seizure like events changed their characteristics after one to two hours to recurrent discharges of 0.8 to 10 s. 20 microM loreclezole blocked the seizure like events in the entorhinal cortex completely 30-80 min after onset of application. The recurrent short discharges in the hippocampus were reliably blocked by 40 muM loreclezole 60-90 min after bath application with incomplete recovery after washout of several hours. The recurrent discharges in the entorhinal cortex were reliably blocked by 80 microM loreclezole applied for 80-100 min. Decreases in [Ca2+]o and associated slow field potentials evoked by repetitive stimulation of the stratum radiatum were depressed in a dose dependent manner, while similar changes induced by alvear stimulation remained almost unaffected. A paired pulse stimulus paradigm used to test for effect of loreclezole on synaptically evoked transient field potentials in normal medium revealed interference with mechanisms involved in frequency potentiation. While responses to alvear stimulation were largely unaffected, the response to a paired pulse stimulus to stratum radiatum was depressed over the whole range of tested stimulus intervals (15 to 150 ms). The findings suggest that loreclezole has effects on different patterns of epileptiform activity induced by extracellular low Mg2+ possibly by interfering with processes leading to frequency potentiation.
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PMID:Effects of the triazole derivative loreclezole (R72063) on stimulus induced ionic and field potential responses and on different patterns of epileptiform activity induced by low magnesium in rat entorhinal cortex-hippocampal slices. 147 Feb 29

In experiments on Wistar male rats it was shown that i.p. administration of verapamil or ryodipine (1,4-dihydropyridine) 15 min before each daily injection of pentylenetetrazol (PTZ) in a subconvulsive dose 30 mg/kg during 28 days significantly delayed the development of PTZ-induced kindling and attenuated kindled seizure reactions during 21-23 days as compared with control. One week after kindling an increase in free Ca2+ concentration in control rat brain synaptosomes by 60% was revealed; the treatment by verapamil and ryodipine prevented this increase. Nevertheless, Ca2+ antagonists studied at least under our experimental conditions inspite of a significant decrease in free Ca2+ concentration in synaptosomes would not completely prevent the development of kindling. Thus, an alteration in calcium homeostasis will not be the only mechanism of plasticity and long-term changes of neurons during kindling.
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PMID:[Organic calcium antagonists verapamil and ryodipine prevent an increase of free calcium in synaptosomes of the rat brain during corazol kindling]. 147 46

Abnormal behavior in epileptic mice (El mice) may be rectified after convulsive seizures. This mechanism was investigated behaviorally through measurements of ethanol-induced sleeping time and locomotor activity, as well as immunohistochemically using a microphotometry system. Decreased ethanol-induced sleeping time and increased ethanol-dependent locomotor activity in El mice as compared to ddY mice (the mother strain of El mice) were rectified by convulsions as well as the intraventricular (IVT) administration of CaCl2, dopamine, or serotonin. Also, the lower dopamine levels in the neostriatum and nucleus accumbens septi in El mice as compared to ddY mice were improved by convulsions as well as the IVT administration of CaCl2. We have previously observed that a lower level of serum calcium in El mice causes a decrease in central biogenic amine synthesis through a calmodulin-dependent system. This may increase the susceptibility to epileptic convulsions and induce abnormal behavior. Combining the present results with our previous observations, we suggest that the convulsions in El mice will be induced when the balance of physiological functions is lost, as may be seen when the biogenic amine syntheses are decreased. The serum calcium level in El mice is increased by convulsions, and an elevated serum calcium level enhances brain biogenic amine synthesis through a calmodulin-dependent system. Subsequently, biogenic amines rectify physiological disorders in El mice.
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PMID:The effect of convulsions on the rectification of central nervous system disorders in epileptic mice. 148 41

Various anticonvulsant drugs were evaluated for their ability to protect against clonic seizures induced in mice by intraventricular injection of the K+ channel blocking peptide dendrotoxin (DTX). Phenytoin, the phenytoin-like anticonvulsant carbamazepine and the broad spectrum drug valproate were effective in this model, whereas the GABA-enhancers diazepam and tiagabine, the NMDA antagonists (+/-)-CPP and (+)-MK-801, the AMPA antagonist NBQX, the antiabsence drug ethosuximide and the Ca2+ channel antagonist nimodipine were inactive. In contrast to the lack of activity of other NMDA antagonists, phencyclidine and ADCI [(+/-)-aminocarbonyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine] were potent antagonists of DTX-induced seizures.
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PMID:Protection against dendrotoxin-induced clonic seizures in mice by anticonvulsant drugs. 150 73

Leukocyte activation is known to involve cell membrane potential changes. Phenobarbital, an anesthetic and anticonvulsant that can inhibit neuronal membrane depolarization, may also affect leukocyte activation. Measuring membrane potential, actin polymerization, chemotaxis, superoxide production, lymphocyte proliferation, intracellular calcium concentration, and cytokine production, we found that phenobarbital at a concentration of 15-30 micrograms/ml, which is considered a therapeutic serum level for controlling seizures, did not affect polymorphonuclear neutrophil (PMN) activation. At levels higher than 100 micrograms/ml, phenobarbital significantly suppressed formylmethionyl-leucyl-phenylalanine (fMLP)-induced chemotaxis. Concentrations greater than 300 micrograms/ml also inhibited phorbol myristate acetate-stimulated membrane potential change. In contrast, 30 micrograms/ml phenobarbital significantly inhibited lymphocyte proliferation stimulated by phytohemagglutinin (PHA) and pokeweed mitogen. This concentration of phenobarbital also suppressed the increase of intracellular free calcium induced by PHA. However, only a higher concentration of phenobarbital (300 micrograms/ml) was able to inhibit PHA-induced interleukin-2 (IL-2) production and suppress the proliferation of PHA-induced IL-2 receptor-bearing lymphocytes. These results suggest that concentrations of phenobarbital associated with anticonvulsive levels do not affect PMN activation but suppress lymphocyte activation, possibly by affecting intracellular signal transduction.
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PMID:Effects of phenobarbital on leukocyte activation: membrane potential, actin polymerization, chemotaxis, respiratory burst, cytokine production, and lymphocyte proliferation. 150 69

The mechanisms that give rise to ischemic brain damage have not been definitively determined, but considerable evidence exists that three major factors are involved: increases in the intercellular cytosolic calcium concentration (Ca++i), acidosis, and production of free radicals. A nonphysiological rise in Ca++i due to a disturbed pump/leak relationship for calcium is believed to cause cell damage by overactivation of lipases and proteases and possibly also of endonucleases, and by alterations of protein phosphorylation, which secondarily affects protein synthesis and genome expression. The severity of this disturbance depends on the density of ischemia. In complete or near-complete ischemia of the cardiac arrest type, pump activity has ceased and the calcium leak is enhanced by the massive release of excitatory amino acids. As a result, multiple calcium channels are opened. This is probably the scenario in the focus of an ischemic lesion due to middle cerebral artery occlusion. Such ischemic tissues can be salvaged only by recirculation, and any brain damage incurred is delayed, suggesting that the calcium transient gives rise to sustained changes in membrane function and metabolism. If the ischemia is less dense, as in the penumbral zone of a focal ischemic lesion, pump failure may be moderate and the leak may be only slightly or intermittently enhanced. These differences in the pump/leak relationship for calcium explain why calcium and glutamate antagonists may lack effect on the cardiac arrest type of ischemia, while decreasing infarct size in focal ischemia. The adverse effects of acidosis may be exerted by several mechanisms. When the ischemia is sustained, acidosis may promote edema formation by inducing Na+ and Cl- accumulation via coupled Na+/H+ and Cl-/HCO3- exchange; however, it may also prevent recovery of mitochondrial metabolism and resumption of H+ extrusion. If the ischemia is transient, pronounced intraischemic acidosis triggers delayed damage characterized by gross edema and seizures. Possibly, this is a result of free-radical formation. If the ischemia is moderate, as in the penumbral zone of a focal ischemic lesion, the effect of acidosis is controversial. In fact, enhanced glucolysis may then be beneficial. Although free radicals have long been assumed to be mediators of ischemic cell death, it is only recently that more substantial evidence of their participation has been produced. It now seems likely that one major target of free radicals is the microvasculature, and that free radicals and other mediators of inflammatory reactions (such as platelet-activating factor) aggravate the ischemic lesion by causing microvascular dysfunction and blood-brain barrier disruption.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Pathophysiology and treatment of focal cerebral ischemia. Part II: Mechanisms of damage and treatment. 150 80

Classification, management and prevention of seizures in children are summarized for clinicians in Papua New Guinea. Seizures are classified as febrile with or without underlying brain pathology, and afebrile, including neonatal fits, infantile spasms, myoclonic jerks, akinetic seizures, tonic clonic fits, petit mal, benign focal, and psychomotor seizures. In all cases the first step is to secure the airway, then do a fingerstick and treat hypoglycemia, and finally stop the fit if it is prolonged with paraldehyde, diazepam, phenobarbitone or phenytoin. A cause for the seizure should be sought: physical exam, especially tympanic membranes and throat, blood slide for malaria, lumbar puncture for signs of meningitis, blood culture, serum calcium, and other chemistries. Some empirical treatments to use for negative findings include: dextrose, calcium gluconate, magnesium SO4, pyridoxine, quinine and Fansidar. Hyperthermia in a febrile child can be reversed with cool sponging. The author recommends prescribing phenobarbitone to prevent subsequent simple febrile seizures if the child has 3 or more, then slowly withdrawing the drug if the child is seizure free for a year. Drug therapy for the various other types of seizures available in Papua New Guinea include sodium valproate by special order, and phenobarbitone, phenytoin, carbamazepine, nitrazepam, ethosuximide, and prednisolone. A table is provided to help select the drug for each seizure type, e.g. ethosuximide for petit mal, prednisolone for infantile spasms, and carbamazepine for various types of focal and psychomotor seizures.
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PMID:Convulsions in children. 150 14

The responses to the glutamate agonist N-methyl-D-aspartate (NMDA) were studied in the sensori-motor cortex of rats with petit mal-like seizures. In a first study, the changes in extracellular concentration of calcium elicited through ionophoretic application of NMDA at various depths in the cortex were measured in vivo. The results show that in the cortex of epileptic rats the NMDA responses are much more widely distributed than in the cortex of control rats. In a second study, a current-source density analysis of the responses elicited through electrical stimulation of the white matter was performed in slices of neocortex in vitro. These findings show that the NMDA-dependent component of the synaptic responses are more widely distributed and of longer duration in the cortex of epileptic rats than in that of control rats. Taken together, these results suggest that in this model of absence epilepsy NMDA-dependent mechanisms are important in the triggering and maintenance of epileptic activity.
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PMID:Responses to N-methyl-D-aspartate are enhanced in rats with petit mal-like seizures. 151 97

A variety of in vitro data suggest that ethanol interferes with N-methyl-D-aspartate (NMDA)-stimulated calcium ion conductance. This effect occurs at ethanol concentrations in blood associated with acute intoxication in the nontolerant human (less than 50 mM) and may involve its selective action at the strychnine-insensitive glycine binding site on the NMDA receptor complex. Moreover, there are in vitro data showing that glycinergic interventions can attenuate ethanol's inhibitory actions on NMDA-mediated transmission. The relevance of these in vitro findings to the intact animal was tested in an incremental electroconvulsive shock (IECS) paradigm using milacemide, a lipophilic prodrug of glycine. In this paradigm, the influence of milacemide on ethanol's ability to antagonize the electrical precipitation of seizures was tested. Doses of 3.2 and 32.0 mg/kg did not change ethanol's antiseizure efficacy, whereas 320.0 mg/kg potentiated ethanol's antiseizure efficacy. The mechanism of potentiation of ethanol's antiseizure efficacy by milacemide is unknown. Potentiation could result from stimulation of chloride ion conductance in the brainstem by glycine liberated from the lipophilic prodrug and acting at the strychnine-sensitive site. Alternatively, unmetabolized milacemide, which accumulates at the highest administered dose, may antagonize NMDA-mediated neural transmission. The latter explanation would be consistent with a role for receptor-gated calcium ion conductance in the mediation of ethanol's actions.
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PMID:Effects of milacemide, a glycine prodrug, on ethanol's antiseizure efficacy. 153 63


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