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

The (Na+ 4 K+)- and Mg2+-dependent ATPase distribution in several brain areas has been investigated in Quaking mutant mice characterized by myelin deficiency. A marked decrease of (Na+ + K+)-ATPase activity has been found in limbic structures, hypothalamus and cerebellum. The Mg2+-dependent activity did not change. A possible involvement of the impairment of the (Na+ + K+)-ATPase activity in the seizure susceptibility of this mice is discussed.
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PMID:The (Na+ + K+)-ATPase activity in brain of Quaking mice. 12 35

We propose than an alarm mechanism is operative in animals, designed to regulate neuromuscular irritability by regulating [Ca2+]. Epinephrine or corticotropin (ACTH), injected intramuscularly into animals, causes a hypercitricemia, resulting in decreased [Ca2+]. This increases muscular excitability to facilitate escape. To avoid over reaction, [Cl-] is shifted into the plasma without a concomitant shift of Na+, thus generating an acidosis and an increase in ionization of Ca. Plasma pH, pCO2, total CO2, and [K+] decrease, and [Mg2+] increases. The acidosis, decrease in K+, and increase in [Mg2+] serve to counteract the effect of the decrease in [Ca2+], to protect against tetany. In the rabbit the hypercitricemia observed upon ACTH administration is accompained by a severe hypocalcemia and drop in blood pressure, resluting in tetanic convulsions. This seems to indicate calcitonin release, independent of the hypercitricemia. Thyroidectomized rabbits show only mild hypocalcemia when given ACTH, but develop a severe acidosis and typical grand mal epileptiform seizures. Administration of ACTH and then calcitonin to the goat, an animal resistant to the effects of ACTH alone, simulates the effect observed in the rabbit with respect to changes in blood components and blood pressure. Changes in the blood in the goat and rabbit resemble those in humans before an epileptic seizure. alpha-Melanotropin, containing a portion of the ACTH sequence, reacts in a manner similar to ACTH but more rapidly.
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PMID:Clinical biochemistry of epilepsy. II. Observations on two types of epileptiform convulsions induced in rabbits with corticotropin. 22 Nov 37

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

Magnesium is an essential cofactor for many enzymatic reactions, especially those involved in energy metabolism. Deficits of magnesium are prevalent due to inadequate intake or malabsorption and due to the renal loss of magnesium that occurs in certain disease states (alcoholism, diabetes) and with drug therapy (diuretics, aminoglycosides, cisplatin, digoxin, cyclosporin, amphotericin B). Protracted deficits of magnesium in humans and animals result in neurological disturbances, including hyperexcitability, convulsions and various psychiatric symptoms ranging from apathy to psychosis, some of which can be reversed with magnesium supplementation, others requiring correction of the dysregulation mechanism. Although the role of magnesium in neuronal function is not completely understood, a lowering of CSF or brain magnesium can induce epileptiform activity and there is an association between decreased CSF magnesium and the development of seizures. CSF concentrations of magnesium are normally higher than magnesium plasma ultrafiltrate (diffusible) concentrations due to the active transport of magnesium across the blood-brain barrier. Under conditions of magnesium deficiency, CSF concentrations decline, although this decline lags behind and is less pronounced than the changes observed in plasma magnesium concentrations. Decreases in CSF magnesium concentrations correlate with the alterations observed in extracellular brain magnesium concentrations in animals following the dietary deprivation of magnesium. CSF magnesium concentrations can readily be repleted following magnesium supplementation, although high dose magnesium therapy, such as that used in the treatment of convulsions in eclampsia, will only increase CSF magnesium concentrations to a very limited degree (approximately 11-18 per cent) above physiological concentrations. Greater increases in CSF magnesium may occur in neonates since neonatal swine, following treatment with magnesium, have CSF magnesium concentrations that are similar to their plasma concentrations. There has been a recent resurgence of interest in magnesium deficiency and its neurological consequences due to the finding that magnesium, at physiological concentrations, blocks N-methyl-D-aspartate (NMDA) receptors in neurones. NMDA receptors are normally activated by glutamate and/or aspartate which represent the principal neurotransmitters for excitatory synaptic transmission in vertebrate CNS. Magnesium deficiency produces epileptiform activity in the CNS which can be blocked by NMDA receptor antagonists. Other mechanisms, including alterations in Na+/K(+)-ATPase activity, cAMP/cGMP concentrations and calcium currents in pre- and postsynaptic membranes, may also be at least partially responsible for the neuronal effects associated with low brain magnesium. Further studies are necessary to increase our understanding of the neurological implications of magnesium deficit in the central nervous system.
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PMID:Brain and CSF magnesium concentrations during magnesium deficit in animals and humans: neurological symptoms. 129 67

The neurotransmitter norepinephrine (NE) has been implicated in both the normal expression of long-term neuronal plasticity and in development of epileptiform bursting. Our studies have focused on the modulatory role of NE in a number of epilepsy models, both acute and chronic. Acutely, reduction of extracellular Mg2+ concentration in in vitro brain slices induced spontaneous and evoked epileptiform activity in both the entorhinal cortex (EC) and dentate gyrus (DG), due largely to removal of the voltage-dependent Mg2+ blockade of N-methyl-D-aspartate receptors. Spontaneous ictal events are most prominent in the EC, suggesting an importance of this area in seizure generation. NE was found to exhibit differential modulation of epileptiform activity in the EC and DG. In the EC, NE, acting via alpha 1-receptors, completely blocked low Mg(2+)-induced epileptiform activity. In contrast, in the DG, NE exhibited a beta-receptor mediated prolongation of the low Mg(2+)-induced ictal events, and enhanced the stimulus-induced ionic and field potential changes. These complementary modulatory actions in the EC and DG, may serve to enhance signal transmission through the DG, while simultaneously reducing EC input noise and exerting a potent antiepileptic action in the EC. Chronically, actions of NE in the DG were examined before and after kindling-induced epilepsy, neuronal plasticity produced by daily high-frequency stimulation. NE, acting on beta 1-receptors, depolarized granule cells, increased input resistance, firing and influx of Ca2+ in response to repetitive stimulation, and elicited long-lasting potentiation of synaptic potentials. In addition, NE acting via alpha 1-receptors, attenuated Ca(2+)-dependent regenerative potentials. After kindling-induced plasticity, there were marked reductions in all these effects of NE on granule cells, changes likely to influence kindling-induced seizures, protecting against further enhancement of excitability once plasticity is in place.
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PMID:Noradrenergic modulation of epileptiform bursting and synaptic plasticity in the dentate gyrus. 133 59

Properties of the interaction between the entorhinal cortex (EC) and the dentate gyrus were studied in a combined EC hippocampal slice preparation in which most of the fiber connectivity within this structure is intact. Epileptiform activity was induced by lowering extracellular Mg2+ concentration. This caused short recurrent discharges in the hippocampus while seizure-like events (SLE) slowly spread from the site of initiation to neighboring areas. At the end of a SLE, the EC, the subiculum and the neocortical area Te2 discharged in synchrony. This activity could develop into a state of recurrent tonic discharges highly synchronized between the different areas. These discharges were insensitive to treatment with currently available antiepileptic drugs. Although the SLE increased neuronal firing and extracellular potassium concentration in the dentate gyrus, this activity had only moderate effects on the activity generated in areas CA3 and CA1. Removing GABAergic inhibition with baclofen and bicuculline caused the spread of SLE from the EC to the dentate gyrus. Slow inhibitory postsynaptic potentials and intrinsic properties of dentate gyrus granule cells appear to underlie the filtering function of the dentate gyrus.
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PMID:The dentate gyrus as a regulated gate for the propagation of epileptiform activity. 133 66

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

Kindling is a form of experimental epileptogenesis in which periodic electrical stimulation of a brain pathway induces a permanently hyperexcitable state. Previous studies suggested that kindling might be explained, at least in part, by an increased sensitivity of brain neurons to NMDA receptor agonists. This possibility was investigated with the use of grease-gap preparations for assaying the depolarizing responses of CA3 and CA1 hippocampal pyramidal cells to amino acid excitants. When studied 1-2 months after the last evoked seizure, CA3 pyramidal cells from kindled rats were five- to sixfold more sensitive to NMDA than CA3 pyramidal cells from controls. A similar, though smaller, effect of stimulation was observed 1 d after the last evoked seizure. The greater potency of NMDA in kindled rats can probably be explained by enhanced expression of NMDA receptors in the presence of a receptor reserve. The stimulation protocol did not alter the ability of Mg2+ to reduce NMDA potency. It also affected neither the response of CA3 pyramidal cells to AMPA [(RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate] nor the response of CA1 pyramidal cells to NMDA or AMPA. In area CA3, the potency of NMDA, but not of AMPA, declined 2.5-4-fold over the 1-2 month experimental period, apparently as a result of increasing age. This age-related loss of sensitivity to NMDA was completely prevented by kindling. These findings suggest that kindling prevents a loss of NMDA receptor function in CA3 pyramidal cells that normally occurs during early adulthood. Such a change could contribute to maintenance of the kindled state.
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PMID:Kindling enhances sensitivity of CA3 hippocampal pyramidal cells to NMDA. 137 64

Magnesium sulfate is used for seizure prophylaxis in patients with preeclampsia. It also has significant effects on calcium metabolism and could, therefore, alter the pressor response to calcium-dependent vasoconstrictors. The present in vivo rat study examined the effect of magnesium sulfate to alter the pressor response to norepinephrine (NE) and angiotensin II (A II). Magnesium doses were chosen to approximate those used in treating preeclampsia. NE resulted in a significant rise in mean arterial pressure (delta MAP, 46 +/- 3.7 mmHg; p < 0.001). A II also resulted in a significant rise in MAP (delta MAP, 23 +/- 3.6 mmHg, p < 0.02). Magnesium sulfate alone had no significant effect on MAP but attenuated the pressor response to both NE (delta MAP, 16 +/- 1.5 mmHg) and A II (delta MAP, 12 +/- 2.5 mmHg). After discontinuation of the magnesium sulfate infusion, the control pressor responses to NE and A II were again seen (delta MAP, 39 +/- 3.5 mmHg and delta MAP, 28 +/- 4.2 mmHg, respectively). Although magnesium sulfate is not a primary antihypertensive agent, it may have effects on blood pressure by attenuating the actions of circulating vasoconstrictors.
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PMID:Effect of magnesium sulfate on the vascular actions of norepinephrine and angiotensin II. 141 60

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


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