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

At present, magnesium treatment is employed routinely in the treatment of hypertension induced by pregnancy (PIH) and preeclampsia in USA with the object of preventing seizures. In USA the treatment of election consists of intravenous infusion of large doses of magnesium sulphate in order to obtain a therapeutic concentration. The anticonvulsive mode of action of magnesium is only partially understood. Magnesium is presumed to block the neuromuscular transmission but a central effect cannot be excluded. Treatment with magnesium has, in addition, an antihypertensive effect. The effect of magnesium on the blood pressure is probably a direct vasodilatory effect which explains the ability of magnesium to reduce the maternal blood pressure. Probably the same mode of action is responsible for the relaxing effect of magnesium on the vascular tone in the umbilical and placental vessels. This can probably explain the favourable effect of magnesium on the birth weight. Even if magnesium treatment implies a potential risk for neonatal hypermagnesemia and hypocalcaemia, only few side effects have been reported.
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PMID:[Magnesium therapy in pregnancy-induced hypertension and pre-eclampsia]. 846 49

To investigate whether prolonged severe swelling would cause irreversible injury to neurons, we exposed hippocampal tissue slices to hypotonic solutions (142 mosmol/kg) and followed the recovery of evoked responses for 5 h. Orthodromically evoked responses increased during hypotonia, except during recurrent waves of spreading depression (SD). After restoring normal osmotic pressure (pi o), evoked potentials became profoundly depressed. Following 30 min exposure, nearly maximal orthodromic responses recovered completely but responses to submaximal stimuli remained depressed, indicating elevated threshold. Following 60 min exposure, orthodromic transmission remained depressed. In slices from young animals, antidromic population spikes recovered completely, but in slices from older rats they remained partly depressed. Withdrawing calcium and raising magnesium concentration before and during hypotonic exposure resulted in modest but significant improvement of the recovery of synaptically transmitted responses, but made no difference for antidromic responses. With [Ca2+]o reduced and [Mg2+]o elevated, electrographic seizures replaced the episodes of SD during low pi o treatment. We conclude that even 60 min of severe hypotonic swelling did not kill CA1 pyramidal cells in tissue from young rats, but in its aftermath synaptic transmission was disrupted. Uptake of calcium may have played a minor role in the impairment of synaptic transmission. We propose hypothetically that post-hypotonic shrinkage of dendrites disrupted the integrity of excitatory synapses.
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PMID:The extent and mechanism of the loss of function caused by strongly hypotonic solutions in rat hippocampal slices. 855 31

In this paper we review our data from in vivo and in vitro experiments with mutant, carbonic anhydrase II (CA II) deficient mice (Car2n/Car2n mutants) compared to their nonmutant littermates (Car2n/+ or +/+). In vivo, mutant mice were more resistant to flurothyl-, pentylenetetrazol, and loud sound-induced seizures than normal littermates. The increased resistance to flurothyl seizures was age dependent for clonic seizures, occurring after 19 days of age and disappearing after 90 postnatal days. In in vitro experiments, synaptic transmission in hippocampal slices from mutant mice were more resistant to hypoxia than synaptic transmission in slices from normal littermates. There was almost no difference in hippocampal CA1 long-term potentiation of synaptic transmission between mutants and nonmutants. However, studying in vitro epileptogenesis, we found hippocampal slices from mutants to be more prone to seizures in the low Mg2+ environment than slices from normal littermates. This striking difference between in vivo and in vitro seizures susceptibility in CA II-deficient mutants suggests and existence of an anticonvulsant factor present in conditions in vivo, but not in vitro. We suggest that extracellular proton concentrations (extracellular pH) acting as N-methyl-D-aspartate (NMDA) receptor antagonist may be such a factor. Mutant mice suffer from severe systemic acidosis that can decrease NMDA receptor function and thus be anticonvulsant in vivo. However in vitro, the steady pH of perfusing solution is relatively alkalinic for mutant mouse slices enhancing the thus NMDA receptor conductance and leading to proconvulsant effects. Thus, the anticonvulsant action of CA inhibition in vivo may be mediated by acidotic extracellular pH rather than an accumulation of CO2 as suggested previously.
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PMID:Anticonvulsant action of carbonic anhydrase inhibition. 871 46

Brain pH is thought to be an influential factor in determining susceptibility to seizures. We compared the susceptibility of brain slices from carbonic anhydrase II (CA II)-deficient mice to epileptiform activity induced by low extracellular [Mg2+], with slices from normal littermates, both bathed in artificial cerebrospinal fluid at pH 7.3. In both entorhinal cortex and hippocampal field CA1, epileptiform activity started earlier in CA II-deficient slices. Raising extracellular [CO2] (20%; extracellular pH, 6.7) reversibly blocked the epileptiform activity in normal, but not in CA II-deficient, slices. The data, combined with previous in vivo findings showing an increased resistance of mutants to seizures, suggest the presence of in vivo anticonvulsant acidosis with long-term compensatory changes that lead to in vitro 'proconvulsant' behavior in CA II-deficient slices clamped at pH 7.3.
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PMID:Increased susceptibility of brain slices from carbonic anhydrase II-deficient mice to low [Mg2+]O-induced seizures. 872 70

Seizure susceptibility waxes and wanes in an apparently circadian manner in many epileptic patients. Fluctuations of melatonin concentration with highest levels during the night and lowest levels in the early morning could be involved in this phenomenon. Therefore, the action of melatonin on epileptic activity was tested. The experiments were carried out on human temporal neocortical slices cut from tissue resected for surgical treatment of epilepsy. Autoradiographic studies were performed on parallel slices with 100-120 pmol 2-[125I]iodomelatonin/l in the absence or presence of unlabelled melatonin. High-affinity binding sites of melatonin could be demonstrated in layers II-V of the temporal cortex. The binding was saturable, specific and occurred with low capacity. In electrophysiological studies, epileptiform field potentials were elicited by omission of Mg2+ from the superfusate and recorded from layers II-V. The frequency of occurrence of epileptiform field potentials was reduced to 0.5 of the initial value with application of melatonin (10 and 100 nmol/l) in each case. This effect was reversible upon washing. The findings favour the hypothesis that melatonin depresses epileptiform neuronal activity through specific neocortical receptors.
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PMID:Melatonin reduces low-Mg2+ epileptiform activity in human temporal slices. 877 50

Exposure of hippocampal slices to Mg2+ free media (0 Mg) has been shown to trigger full production of stimulus-induced seizure activity after restoration of physiological conditions [1]. In the present study employing hippocampal entorhinal cortical slices (HEC), spontaneous epileptiform discharges (SEDs) were induced using 0 Mg treatment following the return of the slices to physiological conditions. To evaluate the effect of sustained epileptiform activity on gene expression in this HEC slice preparation, changes in mRNA levels of the GABAA alpha 1 and alpha 2 and beta CaM Kinase II subunits were measured using in situ hybridization. HEC slices were incubated in oxygenated artificial cerebrospinal fluid (ACSF) in the presence or absence of Mg2+ for 3 h, then placed in oxygenated ACSF containing Mg2+ for up to 3 h. Control slices were maintained in Mg2+ containing ACSF for up to 6 h. Recurrent SEDs were observed in 0 Mg pre-treated slices while no epileptiform discharges were seen in control slices. Following induction of SEDs by 0 Mg pre-treatment, a significant decrease in mRNA encoding GABAA alpha 2 was found in the CA1, CA2, CA3 and dentate gyrus (DG) regions of the hippocampus for up to 3 h after treatment. Levels of mRNA for GABAA alpha 1 and beta CaM Kinase II were not affected. The results document a decrease in GABAA alpha 2 gene expression following the induction of SEDs in the HEC slice preparation and suggest that rapid changes in neuronal gene expression may contribute to long lasting excitability changes associated with the induction of epilepsy.
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PMID:GABAA alpha 2 mRNA levels are decreased following induction of spontaneous epileptiform discharges in hippocampal-entorhinal cortical slices. 879 90

Extracellular recordings were performed in in vitro combined hippocampal-entorhinal cortex (HC-EC) slices obtained from control and amygdala kindled rats to investigate the spread of epileptiform activity from the entorhinal cortex (EC) to the hippocampus (HC). Epileptiform activity was induced by lowering extracellular Mg2+ concentration. In control slices epileptiform activity was in most slices characterized by intericatal discharges and short recurrent discharges in areas CA1 and CA3 and by early seizure like events and late recurrent discharges in the EC and the subiculum. In spite of well preserved anatomical pathways in the combined HC-EC slice in which most of the fibre connectivity between the EC and the dentate gyrus (DG) is intact, seizure like events and late recurrent discharges generated in the EC had only moderate effects on the epileptiform activity in areas CA3 and CA1. In contrast in HC-EC slices obtained from kindled rats epileptiform activity generated in the EC spread to the DG and the areas CA3 and CA1. Kindling facilitates the propagation of seizure like events and late recurrent discharges through the HC-EC slice and appears to alter the filtering function of the DG.
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PMID:Spread of low Mg2+ induced epileptiform activity from the rat entorhinal cortex to the hippocampus after kindling studied in vitro. 889 87

Spontaneous thalamocortical epileptiform activity was elicited in rodent thalamocortical slices by a medium containing no added Mg2+. Multiple varieties of activity were generated in these slices, including simple thalamocortical burst complex (sTBC) activity that resembled the spike-wave discharges of generalized absence epilepsy, and complex thalamocortical burst complex (cTBC) activity that resembled generalized tonic-clonic seizure discharges. In a further pharmacological characterization of this activity, the effects of the broad-spectrum anticonvulsants valproic acid, alpha-methyl-alpha-phenylsuccinimide (the active metabolite of methsuximide) and clonazepam were studied. All three drugs were found to be effective in controlling both sTBC and cTBC activity when applied in clinically relevant concentration ranges. The effectiveness of valproic acid against spontaneous rhythms in vitro was not due to augmentation of GABAergic inhibition. No effect of valproic acid on GABA-activated chloride currents was evident in patch-clamp recordings of acutely isolated thalamic or cortical neurons. The equivalent general clinical and experimental spectrum of action of broadly effective anticonvulsants provided an additional correlation between the clinical efficacy of anticonvulsant drugs and their effects against epileptiform discharges in rodent thalamocortical slices. This further validates spontaneous generalized low-Mg2+ thalamocortical activity as a potentially valuable in vitro model of the primary generalized epilepsies, in which the cellular mechanisms underlying generation and control of these seizure discharges can be studied.
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PMID:Anticonvulsant drug effects on spontaneous thalamocortical rhythms in vitro: valproic acid, clonazepam, and alpha-methyl-alpha-phenylsuccinimide. 892 2

When perfused with a medium containing no added Mg2+, rodent thalamocortical brain slices generate spontaneous generalized thalamocortical discharges of several types. Two of these discharges, termed simple and complex thalamocortical burst complexes (sTBCs and cTBCs), are physiologically and pharmacologically similar to the spike-wave discharges of generalized absence epilepsy and to the discharges underlying generalized tonic-clonic seizures, respectively. In a further characterization of the pharmacology of generalized thalamocortical discharges recorded in rodent thalamocortical slices, the actions of anticonvulsants effective in control of partial and generalized tonic-clonic seizures, but not generalized absence seizures, were studied on these rhythms. The effects of phenytoin, carbamazepine, and phenobarbital were tested against sTBCs and cTBCs recorded in vitro in rodent thalamocortical slices. When applied in clinically relevant concentrations, phenytoin and carbamazepine were very effective in reducing or blocking cTBCs. These drugs were much less effective in controlling sTBCs. Phenobarbital was effective in controlling both sTBCs and cTBCs, but the level of block was greater for cTBCs. Therefore, it appears that sTBCs and cTBCs are quite distinct in their relative sensitivity to anticonvulsant drugs, and this differential sensitivity parallels the relative effectiveness of these drugs in controlling generalized absence and generalized tonic-clonic seizures.
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PMID:Anticonvulsant drug effects on spontaneous thalamocortical rhythms in vitro: phenytoin, carbamazepine, and phenobarbital. 892 3

Lidocaine and MgSO4 are often coadministered to patients with pregnancy-induced hypertension. This study examined whether MgSO4 alters the lidocaine-seizure threshold in the rat and, if so, whether systemic MgSO4 administration is as effective as intracerebroventricular MgSO4 infusion. In Experiment 1, rats were administered 50% MgSO4 or 0.9% NaCl intravenously (IV) (20 microL/h) for 5 days. In Experiment 2, rats were administered 0.9% NaCl, 0.8% MgSO4, or 2.0% MgSO4 (10 microL/h) via intracerebroventricular infusion for 24 h. All rats then underwent continuous IV lidocaine infusion until onset of electroencephalographic seizures. In Experiment 1, plasma [Mg2+] was greater in the MgSO4 group (5.1 +/- 1.5 mg/dL vs 1.8 +/- 0.3 mg/dL) but neither the dose of lidocaine required to induce seizures (MgSO4 = 19 +/- 2 mg/kg; saline = 23 +/- 5 mg/kg) nor brain [Mg2+] (MgSO4 = 794 +/- 17 micrograms/g; saline = 788 +/- 33 micrograms/g) were changed. In Experiment 2, intracerebroventricular MgSO4 increased both brain [Mg2+] (2% MgSO4 = 923 +/- 79 micrograms/g; saline = 788 +/- 35 micrograms/g) and the lidocaine seizure dose (2% MgSO4 = 39 +/- 7 mg/kg; saline = 26 +/- 3 mg/kg). Although intracerebroventricular administration of MgSO4 produces an anticonvulsant effect, chronic hypermagnesemia does not alter whole brain [Mg2+] and therefore offers no protection from lidocaine-induced seizures in this model.
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PMID:The effects of plasma and brain magnesium concentrations on lidocaine-induced seizures in the rat. 894 90


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