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

To determine the utility of the routine practice of obtaining serum chemistry values on children presenting after a seizure, we reviewed the emergency department records of 241 episodes of seizures in pediatric patients. One hundred fifty-five nonfebrile (49 initial, 106 recurrent) and 86 febrile (53 initial, 33 recurrent) convulsive episodes were analyzed. At least one serum chemistry value was obtained in 149 (64%) patients. Clinically significant abnormalities were found in 0/149 serum sodium, 0/148 glucose and blood urea nitrogen, 0/86 calcium, and 0/61 magnesium studies. We concluded that routine determination of serum chemistry values in pediatric patients presenting with a seizure is unnecessary unless specific clinical data strongly suggest otherwise.
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PMID:Absence of serum chemistry abnormalities in pediatric patients presenting with seizures. 160 2

Dihydropyridine calcium antagonists are candidate anticonvulsants, but little is known of their penetration into brain. Nifedipine (NFD) and nimodipine (NMD) pharmacokinetics were compared in mouse blood and brain, and their activity against pentylenetetrazol (PTZ) was assessed. After intraperitoneal (i.p.) injection, both dihydropyridines achieved peak blood and brain concentrations in 5 min. Estimated blood and brain elimination half-lives (t1/2) of NMD (16.7 and 22.4 min) were slightly longer than those of NFD (11.2 and 14.7 min). Brain and blood concentrations correlated with both NFD (r = 0.701, p less than 0.001) and NMD (r = 0.572, p less than 0.001). Injection of the dihydropyridines as a suspension (Tween 80) did not alter brain penetration, although systemic absorption was more erratic. NFD (p less than 0.001), NMD (p less than 0.02), and carbamazepine (CBZ, p less than 0.001) i.p. inhibited PTZ-induced seizures. Brain concentrations of PTZ were not altered by NFD pretreatment. Combining NFD and CBZ was less effective than giving NFD alone (p less than 0.005). NFD (p less than 0.002) and NMD (p less than 0.001) inhibited PTZ seizures after 2-week oral dosing, but low dosing was more effective than high dosing (p less than 0.002). NFD and NMD cross the blood-brain barrier (BBB) in mice and inhibit PTZ seizures. A possible therapeutic window was identified, and NFD and CBZ were less effective in combination than singly. A pharmacodynamic interaction may exist, inhibiting effective use of dihydropyridines as adjunctive therapy in epileptic patients.
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PMID:Dihydropyridine calcium antagonists in mice: blood and brain pharmacokinetics and efficacy against pentylenetetrazol seizures. 162 95

Recordings from the CA3 region of hippocampal slices indicate a developmental change in the divalent cation sensitivity of the response elicited by N-methyl-D-aspartate (NMDA) application. In parallel experiments a developmental difference is demonstrated in the capacity of extracellular calcium to modulate electrographic seizure generation. Calcium modulation of the NMDA-elicited response may contribute to the pronounced capacity of immature hippocampus to generate electrographic seizures. Under these conditions activity dependent changes in extracellular calcium could have a greater influence on ion flow produced by activation of the NMDA receptor. The possibility that changes in the receptor isoform may occur during development would have widespread implications for normal cognitive functions and dysfunctions during brain maturation.
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PMID:Calcium modulation of the N-methyl-D-aspartate (NMDA) response and electrographic seizures in immature hippocampus. 164 82

Although calcium has been implicated in ischemia-induced brain death or dysfunction, many animal studies do not show a beneficial effect of calcium-entry blockers given after resuscitation from a cardiopulmonary arrest (CPA). This may be due to the fact that treatment was started too late; we, therefore, evaluated the effect of the calcium-entry blocker nimodipine administered at the earliest feasible postischemic moment, i.e. at the start of the resuscitation attempts. In anesthetized Wistar rats, CPA was induced by an intra-cardiac injection of KCl, and maintained for 7 min by chest restriction. At the start of the resuscitation attempts, 50 rats were blindly and randomly assigned to intravenous treatment with either nimodipine (10 micrograms/kg over 2 min, followed by 1 micrograms/kg per min for 60 min; n = 25) or saline (n = 25). In the nimodipine group, significantly less rats could be resuscitated (11/25 versus 20/25) and the survival rate at the end of the 7 days evaluation period tended to be lower (5/25 versus 11/25). In the rats surviving after 7 days, there was no difference between both groups in incidence of seizures, neurological status and histological lesions in the hippocampus. It is concluded that nimodipine, in the dose tested and given during resuscitation in this rat model, has a detrimental effect on resuscitability and no beneficial effect on the neurological outcome in the surviving animals.
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PMID:Nimodipine decreases resuscitability in a cardiopulmonary arrest model in the rat. 165 24

The effects of cis-3,4 dichloro-N-2-(1-pyrrolidinyl)cyclo-hexyl-benzamide (U-54494A), an anticonvulsant related to kappa opioids, were studied in vitro on the extracellular electrical activity of the CA1 region of slices of hippocampus in the rat. The effects of U-54494A were compared to those of the kappa opioid agonist trans-3,4 dichloro-N-2-(1-pyrrolidinyl)cyclo-hexyl benzeneacetamide methane sulphonate (U-50488H). Both U-54494A and U-50488H, in concentrations of 50 and 100 microM, respectively, reduced the magnitude of the orthodromically evoked CA1 population spikes after electrical stimulation of the stratum radiatum (100-200 microA, 70 microseconds, 0.1 Hz). Naltrexone (25 microM), or the selective kappa opiate receptor antagonist, 1-cyclopenthyl-5-(1,2,3,4,5,6-hexahydroxy-3,6,11-trimethyl-2 -6-methano-3- benzazocin)-3-pentatone methane sulphonate (WIN 44441-3) (25 microM), prevented the depressant activity of U-54494A (200 microM) on the CA1 population spikes. High calcium (+3mM) solutions prevented the depressant activity of increasing concentrations of both U-54494A and U-50488H on the amplitude of CA1 population spikes. Up to 200 microM, both drugs were ineffective in depressing the epileptiform bursting in CA1, due to 1 mM penicillin or to perfusion of the slice in absence of magnesium ions. The results demonstrate: (1) the inability of U-54494A to show antagonistic activity in two in vitro models of interictal epilepsy; (2) a depressant effect of U-54494A on basal synaptic transmission in the CA1 region of the hippocampus, which may be related to an influence on transneuronal calcium currents and which may be involved in the reported antagonism of ictal epileptic seizures by drugs.
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PMID:In vitro depressant effects of U-54494A, an anticonvulsant related to kappa opioids, in the hippocampus. 165 3

Direct and indirect evidence suggests that Na+/K(+)-ATPase activity is reduced or insufficient to maintain ionic balances during and immediately after episodes of ischemia, hypoglycemia, epilepsy, and after administration of excitotoxins (glutamate agonists). Recent results show that inhibition of this enzyme results in neuronal death, and thus a hypothesis is proposed that a reduction and/or inhibition of this enzyme contributes to producing the central neuropathy found in the above disorders, and identifies potential mechanisms involved. While the extent of inhibition of Na+/K(+)-ATPase during ischemia, hypoglycemia and epilepsy may be insufficient to cause neuronal death by itself, unless the inhibition is severe and prolonged, there are a number of interactions which can lead to a potentiation of the neurotoxic actions of glutamate, a prime candidate for causing part of the damage following trauma. Presynaptically, inhibition of the Na+/K(+)-ATPase destroys the sodium gradient which drives the uptake of acidic amino acids and a number of other neurotransmitters. This results in both a block of reuptake and a stimulation of the release not only of glutamate but also of other neurotransmitters which modulate the neurotoxicity of glutamate. An exocytotic release of glutamate can also occur as inhibition of the enzyme causes depolarization of the membrane, but exocytosis is only possible when ATP levels are sufficiently high. Postsynaptically, the depolarization could alleviate the magnesium block of NMDA receptors, a major mechanism for glutamate-induced neurotoxicity, while massive depolarization results in seizure activity. With less severe inhibition, the retention of sodium results in osmotic swelling and possible cellular lysis. A build-up of intracellular calcium also occurs via voltage-gated calcium channels following depolarization and as a consequence of a failure of the sodium-calcium exchange system, maintained by the sodium gradient.
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PMID:Inhibition of sodium-potassium-ATPase: a potentially ubiquitous mechanism contributing to central nervous system neuropathology. 166 97

1. The effects of BRL 34915 (cromakalim), a potassium channel opener, have been tested on the epileptiform activity elicited by high dose/concentrations of some calcium antagonists in in vivo (diltiazem) and in vitro (diltiazem and verapamil) experiments in rats. 2. Diltiazem (150-300 mg kg-1, i.p.) induced behavioural and electroencephalographic (EEG) seizures that were completely prevented by cromakalim (10 nmol/10 microliters, i.c.v.). Whereas, pentobarbitone (5-10 mg kg-1, i.p.) only prevented the behavioural component of the seizures. 3. In hippocampal slices, verapamil (1.5-2.0 mM) produced, within 30-60 min of perfusion, a CA1 epileptiform bursting in 80% of the experiments. This epileptiform activity was prevented by the cromakalim concentration (50 microM) that did not affect the control CA1 synaptic transmission per se. Pentobarbitone also prevented verapamil-induced epileptiform bursting only at the concentration (100 microM) that also reduced control CA1 synaptic transmission. 4. Diltiazem (1.5 mM) produced a biphasic excitatory-depressant effect within 60 min of perfusion. A CA1 epileptiform bursting appeared in 100% of the experiments within 30 min of perfusion. These excitatory effects were followed by a depression phase, characterized by a reduction of the magnitude of CA1 excitatory postsynaptic potentials (e.p.s.ps) and population spike. 5. The diltiazem-induced epileptiform bursting was prevented by cromakalim at a concentration (50 microM) that did not affect the control CA1 synaptic transmission per se. Pentobarbitone also prevented the diltiazem-induced epileptiform bursting only at a concentration (100 microM) that also reduced the control CA1 synaptic transmission. Both cromakalim (50 microM) and pentobarbitone (100 microM) failed to affect the depressant effects of diltiazem on CA1 hippocampal area. On the contrary, high (3.3mM) calcium solutions prevented both the excitatory and the depressant effects of 1.5 mm diltiazem within 60 min.6. These data indicate an involvement of potassium currents in the epileptiform activity elicited by high doses of diltiazem and verapamil.
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PMID:Cromakalim (BRL 34915) counteracts the epileptiform activity elicited by diltiazem and verapamil in rats. 166 91

The release of putative neurotransmitters [aspartate, glutamate, and gamma-aminobutyric acid (GABA)] was studied in hippocampal slices from adult normal C57BL/6J (B6) and El (epileptic) mice. The El mice, a genetic model of temporal lobe epilepsy, had an average of 86 seizures. Sets of B6 and El hippocampal slices (400 microns thick) were incubated in a series of normal and high potassium (60 mM) buffers in the presence or absence of calcium. The calcium-dependent and calcium-independent potassium-induced release of amino acids was compared in each mouse strain. Release of endogenous amino acids was measured using liquid chromatography with electrochemical detection and was expressed as picomoles of amino acid released per milliliter of incubation buffer per minute of incubation per slice +/- SEM. No significant differences were found between the El and B6 mice for the calcium-dependent potassium-evoked release of glutamate (18.20 +/- 2.62 and 15.41 +/- 3.56), or GABA (17.28 +/- 2.90 and 12.73 +/- 1.37), respectively. Aspartate release, however, was significantly higher in the El mice (6.62 +/- 0.69) than in the B6 mice (3.31 +/- 0.72). These findings suggest that enhanced aspartate release may be related to seizure expression in El mice.
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PMID:Enhanced aspartate release from hippocampal slices of epileptic (El) mice. 167 82

1. During pentylenetetrazol-induced bursting activity which is characteristic intracellular potential change of seizure discharge, intracellular stored calcium is released and moved toward the inner surface of the cell membrane. Calcium is released from lysosome-like granules with morphological changes. During bursting activity, the intracellular free calcium level was higher than the normal state. During bursting activity, intracellular protein of 5 kDa and 15 kDa was changed qualitatively and quantitatively. 2. Primary cultured cerebral cortical neurons of rats and mice showed spontaneous regular firing, and by PTZ application, showed bursting activity. A single potassium channel showed the random open-close state in the normal state and showed burst type open-close state after PTZ application. 3. Primary cultured cerebral cortical neurons of the E1 mouse, the epilepsy animal model, showed developmental defects in neurite extension and content of gangliosides, in addition to their very high susceptibility to convulsions. 4. A new antiepileptic drug, TJ-960, which originates from a mixture of nine herbal drugs, normalized the above-mentioned seizure-related, calcium-related intracellular pathological phenomena. TJ-960 normalized cytochalasin-B-induced looping phenomena and protected the neuron damage induced by cytochalasin B in addition to anticonvulsant action. TJ-960 also completely normalized the cobalt-induced EEG changes and also protected against neuron damage in the hippocampus induced by cobalt application to the cerebral cortex. TJ-960 normalized the developmental defects of the E1 mouse neuron. 5. For better therapy of epilepsy, it is probably necessary to normalize the developmental defects and to protect against neuron damage in addition to inhibition of seizure activity.
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PMID:Cellular physiology of epileptogenic phenomena and its application to therapy against intractable epilepsy. 167 17

Intrahippocampal injection of 1 nmol ouabain, a sodium/potassium (Na+,K(+)-)ATPase inhibitor, produced a necrotic lesion within 4 days, characterised by a massive invasion by foaming macrophages. A lower dose of ouabain (0.1 nmol) produced a more discrete lesion of all groups of neuronal perikarya in the hippocampus, with only a minimal degree of glial infiltration. The neuronal perikaryal death produced in the subicular, CA1 and CA2 regions was only partially decreased by intraperitoneal injections of the anticonvulsants diazepam and MK-801; these drugs were without effect in the CA3 or hilar interneuronal regions. At neither dose of ouabain was there any indication of neuronal loss in brain regions outside the hippocampus, typically produced by prolonged seizure activity. It is suggested that ouabain has a two-fold action, a release of toxic acidic amino acids and a prolonged depolarization of neurons leading to osmolysis or calcium necrosis.
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PMID:The neurotoxicity of ouabain, a sodium-potassium ATPase inhibitor, in the rat hippocampus. 170 75


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