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

We considered the evolution of Ca2+ oscillation dynamics in recurrent seizure-like events. Dynamic system behaviour was characterized in the state space reconstructed from intra- and extracellular [Ca2+] fluctuations simultaneously measured in cultured rat hippocampal slices under low-[Mg2+] conditions. When associated in the seizure-like event, these fluctuations occurred on a restricted set, the attractor, embedded in the full state space with less than five degrees of freedom. Instantaneous relative phase differences indicated field potential-driven phase jumps locked onto seizure-like events. To account for recurrent dynamics, calculations were performed on different extensions of a model for Ca2+ oscillation. These identified bidirectional, asymmetrical coupling of extracellular with intracellular (cytosolic, Ca2+ store, mitochondrial) Ca2+ dynamics as critical in its development.
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PMID:Coupled intra- and extracellular Ca2+ dynamics in recurrent seizure-like events. 1106 84

Magnesium is the second most abundant cation in intracellular fluid and is an essential electrolyte. It has several critically important roles in the body, namely as a cofactor in numerous enzyme systems, and is involved in phosphate transfer, muscle contractility and neuronal transmission. The physiologic role, homeostasis, causes and clinical manifestations of hypo and hypermagnesemia and their therapy are briefly reviewed. Magnesium treatment is emerging as an important adjunct in the management of a few conditions: prevention and control of seizures in eclampsia, cardiovascular diseases, diabetes mellitus, asthma and others.
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PMID:[Magnesium: physiological and clinical relevance. 1: homeostasis and alterations in the metabolism of magnesium]. 1115 89

Several lines of evidence indicate that augmented neuronal activity is associated with increased mitochondrial function, however, the mechanisms of coupling are still unclear. In this study we used a low extracellular Mg2+ concentration and short stimulus trains to evoke neuronal hyperactivity in the form of seizure-like events (SLE) in hippocampal slice cultures. Simultaneous microfluorimetric and electrophysiological techniques were applied to gain insight into changes of Ca2+ concentration in different compartments and into mitochondrial function. SLEs were associated with a large decrease of the extracellular Ca2+ concentration ([Ca2+]e), a spiking increase of the cytoplasmic and a smoothed elevation of the mitochondrial Ca2+ concentration (cytoplasmic concentration [Ca2+]i; intramitrochondrial concentration [Ca2+]m). Following an initial apparent decline in the mitochondrial membrane potential (DeltaPsi) and NAD(P)H autofluorescence, mitochondria depolarized and NADH production was augmented. Furthermore, SLEs were associated with increased oxidation of dihydroethidine (HEt). Our data suggest that intramitochondrial Ca2+ accumulation stimulates NADH production and production of radical oxygen species (ROS). Interestingly, mitochondrial depolarization followed [Ca2+]i and [Ca2+]m changes with a delay implying that electrogenic extrusion of Ca2+ from the mitochondrial matrix might be responsible for the depolarization of the mitochondrial membrane.
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PMID:Ca2+ signalling and changes of mitochondrial function during low-Mg2+-induced epileptiform activity in organotypic hippocampal slice cultures. 1129 91

Spontaneous activity was monitored during pharmacological blockade of GABA(A) receptor function in the CA1 minislice (CA3 was cut off). Synaptic inhibition was blocked by competitive GABA(A) antagonists bicuculline-methiodide (Bic) or GABAZINE (GBZ) and the chloride channel blocker picrotoxin (PTX). Extra- and intracellular recordings using sharp electrodes were carried out in stratum radiatum and pyramidale. At low antagonist concentrations (Bic, GBZ: 1-10 microM; PTX: < 100 microM), synchronized bursts (< 500 ms in duration, interictal activity) were seen as described previously. However, in the presence of high concentrations (Bic, GBZ: 50-100 microM; PTX: 100-200 microM), seizure-like, ictal events (duration 4-17 s) were observed in 67 of 88 slices. No other experimental measures to increase excitability were applied: cation concentrations ([Ca2+]o = 2 mM, [Mg2+]o = 1.7 mM, [K+]o = 3 mM) and recording temperature (30-32 degrees C) were standard and GABA(B)-mediated inhibition was intact. In whole-slice recordings prominent interictal activity, but fewer ictal events were observed. A reduced ictal activity was also observed when interictal-like responses were evoked by afferent stimulation. Ictal activity was reversibly blocked by antagonists of excitatory transmission, CNQX (40 microM) or D-AP5 (50 microM). Disinhibition-induced ictal development did not rely on group I mGluR activation as it was not prevented in the presence of group I mGluR antagonists (AIDA or 4CPG). (RS)-3,5-DHPG prevented the induction and reversed the tertiary component of the ictal event through a group I mGluR-independent mechanism.
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PMID:Seizure-like activity in the disinhibited CA1 minislice of adult guinea-pigs. 1131 41

The effect of nantenine, an aporphine alkaloid, on ATPase K+-dependent dephosphorylation was evaluated using p-nitrophenylphosphate (p-NPP) as substrate. Basal K+-p-NPPase activity was significantly increased with 3 x 10(-4) M, remained unchanged with 3 x 10(-6) M, 3 x 10(-5) M but was reduced with 7.5 x 10(-4) M and 1 x 10(-3) M nantenine, whereas Mg2+-p-NPPase activity was not modified. Kinetic studies showed that K+-p-NPPase inhibition by nantenine is competitive to KCl but non-competitive to substrate p-NPP, whereas K+-p-NPPase stimulation by nantenine is non-competitive to KCl but competitive to p-NPP. These data suggest that there may be two acceptor sites for nantenine in p-NPPase, one eliciting stimulation and the other inhibition of K+-dependent p-NPP hydrolysis. Considering the biphasic action of nantenine on seizures and the correlation between decreased ATPase activity and seizure development, alkaloid anticonvulsant effect observed at low nantenine doses is attributable to the stimulation of phosphatase activity whereas the convulsant effect at high alkaloid doses seems related to Na+, K+-ATPase inhibition.
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PMID:In vitro dose dependent inverse effect of nantenine on synaptosomal membrane K+-p-NPPase activity. 1131 51

Interictal and ictal discharges are recorded from limbic structures in temporal lobe epilepsy patients. In clinical practice, interictal spikes are used to localize the epileptogenic area, but they also are assumed to promote ictal events. Here I review data obtained from combined slices of mouse hippocampus-entorhinal cortex that indicate an inverse relation between interictal and ictal events. In this preparation, application of 4-aminopyridine or Mg2+-free medium induce (a) interictal discharges that originated from CA3 and propagate (via the Schaffer collaterals) to CA1 and entorhinal cortex, to return to the hippocampus through the dentate area; and (b) ictal discharges that initiate in the entorhinal cortex and propagate to the hippocampus via the dentate gyrus. Interictal activity occurs throughout the experiment (up to 6 h), whereas ictal discharges disappear after 1-2 h. Schaffer collateral cut abolishes interictal discharges in CA1, entorhinal cortex, and dentate and reestablishes entorhinal ictal discharges. Moreover, ictal discharge generation in the entorhinal cortex after Schaffer collateral cut is prevented by mimicking CA3 activity with rhythmic electrical stimulation of CA1 outputs. Thus hippocampal interictal activity controls the ability of the entorhinal cortex to generate seizures. It also may be proposed that Schaffer collateral cut may model the epileptic condition in which CA3 damage results in loss of hippocampal control over the entorhinal cortex. In conclusion, these experiments demonstrate that interictal activity controls rather than promotes ictal events, and functional integrity of CA3 constitutes a critical control mechanism in temporal lobe epilepsy.
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PMID:Do interictal discharges promote or control seizures? Experimental evidence from an in vitro model of epileptiform discharge. 1152 Mar 13

2-Methyl-4-oxo-3H-quinazoline-3-acetyl piperidine (Q5), a selective inhibitor of the fast-desensitising component of transmembrane Ca2+ ion influx to (S)-alpha-amino-3-hydroxy-5-methyliso-xazole-4-propionate ((S)-AMPA) was tested for possible anticonvulsant effects in the low-[Mg2+] model of experimental epilepsy. Evolutionary analysis of burst parameters such as half-width, decay time constant, burst multiplicity, instantaneous frequency and amplitude disclosed an approximate doubling of half-width within periods of interictal activity, being predictive for the onset of seizure-like events (SLEs). We found that SLEs observed in the CA3 region of rat hippocampal slices were suppressed by the application of 50 microM Q5. These results suggest an AMPA receptor function shaping the dynamics of spontaneous epileptiform activity.
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PMID:A glutamate receptor subtype antagonist inhibits seizures in rat hippocampal slices. 1193 Jan 36

Infantile spasms (IS) are so typically associated with West syndrome that the term IS, properly referred to as a seizure type, is currently used synonymously with this severe infantile epilepsy. This chapter reviews some clinical and experimental observations relevant to IS pathophysiology with particular regard to maturational aspects that may account for IS age-related expression. Neither the cortical nor the brain stem generator hypotheses account for all the clinical features of IS. It is suggested that IS are generated whenever a cortical discharge is able to influence some archaic circuit located putatively in the brain stem through either an excitatory or a disinhibitory mechanism. This may occur with the highest probability during a developmental window in which IS typically occur, when N-methyl-D-aspartate (NMDA) transmission is particularly facilitated due a reduced sensitivity of NMDA receptors to the Mg2+ block. Interestingly, in this age range (0-18 postnatal day in rat), flexion spasms can be elicited experimentally by NMDA administration. These data provide an important key to further investigating IS pathophysiology, thus allowing us to design more effective strategies aimed at counteracting this harmful infantile epilepsy.
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PMID:Brain maturational aspects relevant to pathophysiology of infantile spasms. 1204 Sep 1

We have determined the properties of seizures induced in vitro during the first postnatal days using intact rat cortico-hippocampal formations (CHFs) and extracellular recordings. Two main patterns of activity were generated by nominally Mg2+-free ACSF in hippocampal and cortical regions: ictal-like events (ILEs) and late recurrent interictal discharges (LRDs). They were elicited at distinct developmental periods and displayed different pharmacological properties. ILEs were first observed in P1 CHFs 52 +/- 7 min after application of low-Mg2+ ACSF (frequency 1.5 +/- 0.3 h-1, duration 86 +/- 3 s). There is a progressive age-dependent maturation of ILEs characterized by a decrease in their onset and an increase in their frequency and duration. ILEs were abolished by d-APV and Mg2+ ions. From P7, ILEs were followed by LRDs that appeared 89 +/- 8 min after application of low-Mg2+ ACSF (frequency approximately 1 Hz, duration 0.66 s, amplitude 0.31 +/- 0.03 mV). LRDs were no longer sensitive to d-APV or Mg2+ ions and persisted for at least 24 h in low-Mg2+ or in normal ACSF. ILEs and LRDs were synchronized in limbic and cortical regions with 10-40 ms latency between the onsets of seizures. Using a double chamber that enables independent superfusion of two interconnected CHFs, we report that ILEs and LRDs generated in one CHF propagated readily to the other one that was being kept in ACSF. Therefore, at a critical period of brain development, recurrent seizures induce a permanent form of hyperactivity in intact brain structures and this preparation provides a unique opportunity to study the consequences of seizures at early developmental stages.
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PMID:Persistent epileptiform activity induced by low Mg2+ in intact immature brain structures. 1237 21

Cyclosporine A (CsA) neurotoxicity is a common cause of seizures in transplant patients and others receiving immunosuppressive therapy. CsA at concentrations higher than the levels estimated for cerebrospinal fluid of the patients suffering from seizure attacks was ineffective to induce epileptiform field potentials (EFP) in in vitro brain-slice preparation. The aim of this study was to test the effect of CsA at lower concentrations on neuronal activity. Guinea-pig hippocampal slices were exposed to artificial cerebrospinal fluid containing CsA (0.1-2 microM). Furthermore, the effects of CsA (0.25-10 microM) were tested on EFP elicited by omission of Mg2+ from superfusate. Low concentrations of CsA (0.1-0.25 microM) induced EFP while higher doses (0.5-2 microM) failed to decrease the seizure threshold. CsA at concentrations of 0.25 and 1 microM had no significant effect on the low Mg2+-induced EFP. Higher CsA concentration (10 microM) strongly suppressed EFP. The results indicate that CsA at doses that are probably clinically relevant increases the neuronal excitability.
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PMID:Epileptogenic effect of cyclosporine in guinea-pig hippocampal slices. 1245 73


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