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

Glial cells in primary mixed cultures or purified astrocyte cultures from mouse cortex respond to reduced extracellular calcium concentration ([Ca2+]e) with increases in intracellular calcium concentration ([Ca2+]i) that include single-cell Ca2+ oscillations and propagated intercellular Ca2+ waves. The rate and pattern of propagation of low [Ca2+]e-induced intercellular Ca2+ waves are altered by rapid perfusion of the extracellular medium, suggesting the involvement of an extracellular messenger in Ca2+ wave propagation. The low [Ca2+]e-induced Ca2+ response is abolished by thapsigargin and by the phospholipase antagonist U73122. The low [Ca2+]e-induced response is also blocked by replacement of extracellular Ca2+ with Ba2+, Zn2+, or Ni2+, and by 100 microM La3+. Glial cells in lowered [Ca2+]e (0.1-0.5 mM) show an increased [Ca2+]i response to bath application of ATP, whereas glial cells in increased [Ca2+]e (10-15 mM) show a decreased [Ca2+]i response to ATP. These results show that glial cells possess a mechanism for coupling between [Ca2+]e and the release of Ca2+ from intracellular stores. This mechanism may be involved in glial responses to the extracellular environment and may be important in pathological conditions associated with low extracellular Ca2+ such as seizures or ischemia.
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PMID:Extracellular calcium sensing by glial cells: low extracellular calcium induces intracellular calcium release and intercellular signaling. 923 16

The ATP-dependent glutamate uptake system of synaptic vesicles was investigated in epileptic (EL) mice to determine whether glutamate uptake activity correlates with seizure susceptibility or development. Given the focal seizure onset, glutamate uptake activity was measured in four separate brain regions: cerebrum (minus hippocampus), hippocampus, cerebellum, and brain stem. The EL values were compared to those of age-matched controls; DDY and ABP/LeJ (ABP) mice. The glutamate uptake specific activity for EL cerebrum was significantly higher than that for the control mice (approx. 400 days old), but was not elevated prior to seizure onset (46 days old). No difference in glutamate uptake was observed between the strains in the other brain regions. We conclude that increased synaptic vesicle glutamate uptake is brain-region specific (cerebrum) and is associated with the development or maintenance, rather than the initial cause, of seizures in the EL model of epilepsy.
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PMID:Synaptic vesicle glutamate uptake in epileptic (EL) mice. 930 8

To date, the electrophysiological properties of glial cells located in reactive scar tissue are unknown. To address this issue two subtypes of hippocampal glial cells, located in thin vital slices of normal or gliotic brain tissue, were analysed for their voltage controlled ion channels using the patch-clamp technique. Reactive gliosis was induced in adult rats by a single peritoneal injection of kainic acid. The intensity of the following seizures was rated ascending from 1 to 6. Rats which exhibited seizures of level 3 or higher showed, within three days, a marked loss of pyramidal cells (60% in CA1 and CA3) and an increase in the density of glial fibrillary acidic protein immunostaining, representing an apparent increase in the number and size of astrocytes in all layers of the hippocampal CA1 subfield. Reactive and normal astrocytes of one subtype, electrophysiologically characterized by time-independent potassium currents, did not significantly differ in membrane potential and potassium conductivity. Glutamine synthetase-positive, but mostly glial fibrillary acidic protein-negative, glial cells (presumably representing immature astrocytes) were also included in this study. This subtype of glial cells showed several voltage- and time-dependent potassium currents and, under control conditions, tetrodotoxin-sensitive voltage-gated Na+ channels, which were almost completely lost after reactive gliosis. Another part of this study focuses on the sensitivity of reactive and control glial cells for extracellular ATP. Several in vitro studies suggest that P2 purinergic receptors on glial cells could trigger the induction of reactive gliosis. In contrast to results described on cultured astrocytes, we found in situ that hippocampal glial cells were not sensitive to ATP or stable P2 receptor agonists in control or in gliotic brain slices. In summary, the presence of at least two different subtypes of hippocampal astrocytes was demonstrated for control as well as for gliotic brain tissue. A dramatic down-regulation of tetrodotoxin-sensitive sodium channels in one subpopulation of reactive astrocytes was shown. This result supports the hypothesis that the presence of active neurons could be required to maintain glial voltage-gated sodium channels. Furthermore, we conclude that there is no longtime expression of P2 purinoceptors on hippocampal astrocytes in situ, and therefore the involvement of astrocytic ATP receptors in the genesis of reactive gliosis is unlikely.
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PMID:Qualitative analysis of membrane currents in glial cells from normal and gliotic tissue in situ: down-regulation of Na+ current and lack of P2 purinergic responses. 931 33

The creatine kinase (CK) reaction is thought to be important in coupling ATP metabolism and regulating ADP concentration in tissues with high and variable ATP turnover, including cerebral gray matter (GM). There is low phosphocreatine (PCr), low CK reaction rates, and high mitochondrial CK (MiCK) isoenzyme activity in GM compared to white matter (WM). To compare the CK reaction in GM and WM when ATP metabolism is high, CK reactants and reaction rates were measured in predominantly GM and WM slices in vivo in 2 and 14-day old piglets during pentylenetetrazole (PTZ) seizures using 31P nuclear magnetic resonance (NMR) 1-dimensional chemical shift imaging (CSI). Arterial pressure, temperature, and blood gasses were stable at both ages. Before seizures, the PCr/nucleoside triphosphate (NTP) ratio was higher in WM than GM at both ages with a developmental increase seen in WM. The CK reaction rate constant increased in both regions between 2 and 14 days. During seizures, PCr/NTP increased in GM at 14 days due to increased PCr while the ratio and PCr decreased in WM. The NTP was more stable in WM and GM at both ages. The CK reaction rate decreased in both regions more at 2 than at 14 days. Thus, brain ATP, deduced from NTP, is stable during seizures in the piglet. In GM stable ATP is associated with a unique increase in PCR concentration.
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PMID:In vivo phosphocreatine and ATP in piglet cerebral gray and white matter during seizures. 947 37

The incidence of clinical seizures is highest in the newborn period. At this developmental stage seizures have many causes, with hypoxia and ischemia thought to be the most common. In rat pups hypoxia produces seizures most frequently at 10-12 d of age. Brain cellular energy metabolism increases between 5 and 25 d of age in the rat, as indicated in vivo by the phosphocreatine (PCr)/nucleoside triphosphate (NTP) ratio measured by 31P nuclear magnetic resonance (NMR) spectroscopy. Brain PCr/NTP ratios are approximately the same in 10-12-d-old rats and human term newborns, the ages of high seizure susceptibility. Thus, low Cr or PCr may be important in susceptibility to hypoxic seizures in the metabolically immature brain. To test this hypothesis, rat pups were injected with Cr for 3 d before exposing them to hypoxia on postnatal d 10 or 20. Before and during hypoxia, the electrocortical activity or 31P nuclear magnetic resonance spectra were measured. At 10 but not 20 d, Cr injections increased brain PCr/NTP ratios, decreased hypoxia-induced seizures and deaths, and enhanced brain PCr and ATP recoveries after hypoxia. Thus, Cr protects the metabolically immature brain from hypoxia-induced seizures and, perhaps, from cellular injury. These results may be directly relevant to the human newborn.
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PMID:Creatine increases survival and suppresses seizures in the hypoxic immature rat. 972 22

Fish venoms can be lethal for Vertebrates. The effect depends of dose and subject, more than incriminated fish. The most constant symptom is a violent pain; but the serious pharmacological effects are respiratory and heart failure with marked hypotension and cardiac perturbations, neurologic damage, such as seizure and coma. Experimentation is difficult due to venom instability. Activity is lost by distilled water, lyophilisation in buffers, several successive freezing and defreezing. In addition, when venom is broken, other pharmacological effects are evidenced, for instance, with Synanceia verrucosa venom, hypertensive phase takes the place of hypotension. It is difficult to distinguish toxin effect from this of denaturation products of the toxin. Noradrenaline is present in Synanceia venom, and it seems that acetylcholine exists in some venom, at least when diluted in saline solution. Other biological active products are present. Purified toxins allow pharmacological investigations. Stonefish venom is better studied, because venomous glands contain relatively high venom quantity. Stonustoxin from Synanceia horrida exerts its action through NO-synthase liberation, and its primary action can be attributed to its potent vasorelaxant activity, causing a rapid, marked and irreversible hypotension. Trachynilysin, from Synanceia trachynis, causes massive release and depletion of acetylcholine and damage to nerve and muscle fibres, which can account for the inhibition of neuromuscular function, and skeletal paralysis. But the used doses are not compatible with respiratory arrest. Verrucotoxin from Synanceia verrucosa activates potassium channels dependent from ATP; this can explain damage, and probably neurologic and respiratory distress.
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PMID:[Pharmacological properties of fish venoms]. 975 86

The Pi peak in a 31P NMR spectrum of the brain can be deconvoluted into six separate Lorentzian peaks with the same linewidth as that of the phosphocreatine peak in the spectrum. In an earlier communication we showed that the six Pi peaks in normal brain represent two extracellular and four intracellular compartments. In that report we have identified the first of the extracellular peaks by marking plasma with infused Pi, thereby substantially increasing the amplitude of the single peak at pH 7.35. 2-Deoxyglucose-6-phosphate (2-DG-6-P) was placed in the brain interstitial space by microdialysis. The resulting 2-DG-6-P peak was deconvoluted into three separate peaks. The chemical shift of the principle 2-DG-6-P peak gave a calculated pH of 7.24 +/- 0.02 for interstitial fluid pH, a value that agreed well with the pH of the second extracellular Pi peak at pH 7.25 +/- 0.01. We identified the intracellular compartments by selectively stressing cellular energy metabolism in three of the four intracellular spaces. A seizure-producing chemical, flurothyl, was used to activate the neuron, thereby causing a demand for energy that could not be completely met by oxidative phosphorylation alone. The resulting loss of high-energy phosphate reserves caused a significant increase in intracellular Pi only in those cells associated with the Pi peak at pH 6.95 +/- 0.01. This suggests that this compartment represents the neuron. Ammonia is detoxified in the astrocyte (glutamine synthetase) by incorporating it into glutamine, a process that requires large amounts of glucose and ATP. The intraarterial infusion of ammonium acetate into the brain stressed astrocyte energy metabolism resulting in an increase in the Pi of the cells at pH of 7.05 +/- 0.01 and 7.15 +/- 0.02. This finding, coupled with our observation that these same cells take up infused Pi probably via the astrocyte end-foot processes, lead us to conclude that these two compartments represent two different types of astrocytes, probably protoplasmic and fibrous, respectively. As a result of this study, we now believe the brain contains four extracellular and four intracellular compartments.
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PMID:NMR-based identification of intra- and extracellular compartments of the brain Pi peak. 983 54

Status epilepticus (SE), i.e. ongoing seizures of more than 30 min duration, gives rise to bilateral pan-necrotic lesions of the substantia nigra, pars reticulata (SNPR). These are known to be preceded by an initial increase, followed by a depression of metabolic rate, and by failure of the bioenergetic state, suggesting mitochondrial dysfunction. We have previously shown that the spin trap alpha-phenyl-N-tert-butyl nitrone (PBN) prevents the lesions caused by 45 min of SE from occurring, in spite of ongoing seizure activity. In this article, we demonstrate that PBN, given 30 min before seizure induction, reduces or prevents the decrease in ATP concentration and adenylate energy charge, without significantly reducing the amount of lactate accumulated, or the decrease in intracellular pH (pHi). The results suggest that the spin trap nitrone preserves the structural and functional integrity of SNPR neurons by protecting the mitochondria against oxidative damage.
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PMID:The effect of alpha-phenyl-N-tert-butyl nitrone on bioenergetic state in substantia nigra following flurothyl-induced status epilepticus in rats. 1035 42

Preconditioning with sublethal ischemia attenuates the detrimental effects of subsequent prolonged ischemic insults. This research elucidates potential in vivo cross-tolerance between different neuronal death-generating treatments such as kainate administration, which induces seizures and global ischemia. This study also investigates the effects of a mild epileptic insult on neuronal death in rat hippocampus after a subsequent, lethal epileptic stress using kainic acid (KA) as a model of epilepsy. Three preconditioning groups were as follows: group 1 was injected with 5 mg/kg KA before a 6-minute global ischemia; group 2 received a 3-minute global ischemia before 7.5 mg/kg KA; and group 3 was injected with a 5-mg/kg dose of KA before a 7.5-mg/kg KA injection. The interval between treatments was 3 days. Neuronal degeneration, revealed by the silver impregnation method and analysis of cresyl violet staining, was markedly reduced in rats preconditioned with a sublethal ischemia or a 5-mg/kg KA treatment. Labeling with terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'triphosphate-biotin nick-end labeling and DNA laddering confirmed the component of DNA fragmentation in the death of ischemic and epileptic neurons and its reduction in all preconditioned animals. The current study supports the existence of bidirectional cross-tolerance between KA excitotoxicity and global ischemia and suggests the involvement of adenosine A1 receptors and sulfonylurea- and ATP-sensitive K+ channels in this protective phenomenon.
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PMID:Mutually protective actions of kainic acid epileptic preconditioning and sublethal global ischemia on hippocampal neuronal death: involvement of adenosine A1 receptors and K(ATP) channels. 1059 33

Bilateral intracerebroventricular infusion of dl-homocysteic acid (DL-HCA) (600 nmol on each side) to immature 12-day-old rats induced generalized clonic-tonic seizures, recurring frequently for at least 90 min, with a high rate of survival. Electrographic recordings from sensorimotor cortex, hippocampus, and striatum demonstrated isolated spikes in the hippocampus and/or striatum as the first sign of dl-HCA action. Generalization of epileptic activity occurred during generalized clonic-tonic seizures, but electroclinical correlation was very low; dissociation between EEG pattern and motor phenomena was common. Seizures were accompanied by large decreases of cortical glucose and glycogen and by approximately 7- to 10-fold accumulation of lactate. ATP and phosphocreatine (PCr) levels remained unchanged even during longlasting (3 h) convulsions. Metabolite levels became normalized during the recovery period (24 h). The examination of the effect of selected antagonists of NMDA [AP7 (18.5 and 37 mg/kg, respectively), MK-801 (0.5 mg/kg)] and non-NMDA [NBQX (10, 15 and 30 mg/kg, respectively)] receptors revealed that seizures could be attenuated or prevented (depending on the dose employed) by antagonists of both NMDA and non-NMDA receptors, as evaluated not only according to the suppression of behavioral manifestations of seizures, but also in terms of the protection of metabolite changes accompanying seizures. All antagonists employed, when given alone in the same doses as those used for seizure protection, did not influence metabolite levels, with the exception of increased glucose concentrations. Furthermore, the pronounced anticonvulsant effect could be achieved by the combined treatment with low subthreshold doses of NMDA (AP7) and non-NMDA (NBQX) receptor antagonists, which may be of potential significance for a new approach to the treatment of epilepsy.
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PMID:Behavioral and metabolic changes in immature rats during seizures induced by homocysteic acid: the protective effect of NMDA and non-NMDA receptor antagonists. 1068 99


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