Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hydroethidine is reported to be selectively oxidized to ethidium by superoxide. Using digital imaging and fluorescence microscopy it is possible to evaluate neuronal ethidium accumulation in specific brain regions of rats damaged in the lithium-pilocarpine model of status epilepticus. Intravenous or intraperitoneal administration of hydroethidine prior to 1 h of status epilepticus produced diffuse cytosolic distribution of ethidium fluorescence suggesting an increased neuronal production of superoxide that was not observed in control animals. A significantly increased number of neurons with the enhanced ethidium fluorescence was observed in parietal cortex, piriform cortex, perirhinal cortex, lateral amygdala, mediodorsal thalamus and laterodorsal thalamus, suggesting superoxide as a mechanism of neuronal injury in those regions. Other regions injured by lithium-pilocarpine seizures, such as the basolateral amygdala and hippocampus, did not demonstrate the enhanced neuronal ethidium fluorescence. In such regions it is possible that superoxide is not a mechanism of injury or that 1 h of status epilepticus is not sufficient to produce superoxide or other reactive oxygen species.
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PMID:Hydroethidine detection of superoxide production during the lithium-pilocarpine model of status epilepticus. 1207 44

Changes in electrical activity, ionic microenvironments, and intracellular Ca concentration were measured during recurrent seizures induced by low Mg in slices and slice cultures. In both preparations, initial seizure-like events (SLEs) changed after some time into drug-refractory late recurrent discharges. In slice cultures, there was considerable cell loss in all hippocampal areas after 2 h of status epilepticus. During recurrent SLEs, the NAD(P)H autofluorescence declined, as did intramitochondrial calcium signals, indicating mitochondrial damage. At the same time, ethidium signals indicated increased radical oxygen species production. These alterations could be reduced by alpha-tocopherol, which also protected slice cultures against status epilepticus-induced cell death.
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PMID:Coupling of electrical and metabolic activity during epileptiform discharges. 1212 15

Generation of free radicals may have a key role in the nerve cell damage induced by prolonged or frequently recurring convulsions (status epilepticus). Mitochondrial function may also be altered due to production of free radicals during seizures. We therefore studied changes in field potentials (fp) together with measurements of extracellular, intracellular, and intramitochondrial calcium concentration ([Ca(2+)]e, [Ca(2+)]i, and [Ca(2+)]m, respectively), mitochondrial membrane potential (deltapsi), NAD(P)H auto-fluorescence, and dihydroethidium (HEt) fluorescence in hippocampal slice cultures by means of simultaneous electrophysiological and microfluorimetric measurements. As reported previously, each seizure-like event (SLE) resulted in mitochondrial depolarization associated with a delayed rise in oxidation of HEt to ethidum, presumably indicating ROS production. We show here that repeated SLEs led to a decline in intracellular and intramitochondrial Ca(2+) signals despite unaltered Ca(2+) influx. Also, mitochondrial depolarization and the NAD(P)H signal became smaller during recurring SLEs. By contrast, the ethidium fluorescence rises remained constant or even increased from SLE to SLE. After about 15 SLEs, activity changed to continuous afterdischarges with steady depolarization of mitochondrial membranes. Staining with a cell death marker, propidium iodide, indicated widespread cell damage after 2 h of recurring SLEs. The free radical scavenger, alpha-tocopherol, protected the slice cultures against this damage and also reduced the ongoing impairment of NAD(P)H production. These findings suggest involvement of reactive oxygen species (ROS) of mitochondrial origin in the epileptic cell damage and that free radical scavenging may prevent status epilepticus-induced cell loss.
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PMID:Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures. 1246 17

We studied the efficacy and safety of midazolam given as a continuous infusion in the treatment of refractory generalized convulsive status epilepticus (RGCSE). We carried out a prospective, open study, in 19 patients (11 men) with RGCSE in the intensive care unit at Firat Medical Center in Elazig. When intravenous administration of 0.3 mg/kg diazepam (three times at 5-min intervals), 20 mg/kg phenytoin, and 20 mg/kg phenobarbital failed to bring the episode under control, patients were administered an intravenous bolus of midazolam (200 microg/kg) followed by a continuous infusion at 1 microg/kg min. The dose was increased by 1 microg/kg min every 15 min until the episode of seizure was brought under control. The time from beginning of treatment to control of seizures, infusion rate, and side-effects were monitored. The mean age of the patients was 40.4 years (range 16-87 years). The clinical etiology of RGCSE was idiopathic epilepsy (6 cases), anoxicischemic cerebral insult due to cardiac arrest (3), viral encephalitis (2), intrahemispheric hematoma due to hemorrhagic stroke (1), cerebral infarct due to ischemic stroke (1), pituitary adenoma (1), post-traumatic epilepsy (1), renal failure (1), tuberculous meningitis (1), and unknown (2). In eighteen (94.7%) patients, seizures were completely controlled in a mean time of 45 min (range, 5-120 min) at a mean infusion rate of 8 microg/kg min (range, 3-21 microg/kg min). In one patient seizures did not stop. Midazolam administration did not cause any significant change in blood pressure, heart rate, oxygen saturation, or respiratory status. The mean time to full consciousness for patients after stopping the infusion was 1.6 hours (range, 2.0-8.5 hours). The mean infusion duration of midazolam was 14.5 hours (range, 12-25 hours). Midazolam is an effective and safe drug to control RGCSE, and may represent a substantial improvement over current therapeutic approaches such as pentobarbital anesthesia.
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PMID:Continuous infusion of midazolam in the treatment of refractory generalized convulsive status epilepticus. 1253 86

Public awareness of the dangers of chemical and biological warfare has been heightened in recent times. In particular, chemical nerve agents such as soman and its analogs have been developed and used in war as well as recent incidents, such as in Iraq and Japan. Soman, a rapid acting acetylcholinesterase inhibitor, produces a status epilepticus that leads to extensive neuropathology in vulnerable brain regions (eg, piriform cortex and hippocampus). This study was undertaken to determine whether oxidative mechanisms are involved in brain pathology during soman toxicity. Intracellular thiols such as glutathione (GSH) and protein sulfhydryls (PrSH) are among the most critical antioxidants used to combat oxidative stress. Here we report that during the seizure phase (1 h post soman exposure), PrSH levels in piriform cortex and hippocampus were decreased without changes in glutathione (GSH) levels. However, by 24 h post soman exposure (pathology phase), GSH levels were decreased by nearly 50% in the piriform cortex with a corresponding decrease in PrSH groups. The shift to a more oxidized thiol status indicates that oxygen free radicals likely participate in the neuropathology associated with soman-induced seizures.
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PMID:Alterations in brain glutathione homeostasis induced by the nerve gas soman. 1283 22

The low Mg2+ model of epilepsy in organotypic hippocampal slice cultures is used to elucidate the mechanism underlying neuronal cell death following sustained epileptiform activity. However, the high oxygen tension of 95% widely used in this model is capable of inducing neuronal cell death by itself. Here we demonstrate that even under normoxic conditions 1h of epileptiform activity induced neuronal cell death as assessed by Propidium Iodide uptake. We conclude that hyperoxia is not essential for status epilepticus induced neuronal cell death in this model.
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PMID:Hyperoxia is not an essential condition for status epilepticus induced cell death in organotypic hippocampal slice cultures. 1513 68

Early surgical removal of a dysplastic hemisphere appears to be beneficial for neonates with hemimegalencephaly and medically resistant seizures. We analyzed the changes in the cerebral regional oxygen saturation index in a neonate with tuberous sclerosis and right hemimegalencephaly (1) during seven episodes of right hemisphere electroencephalographic status epilepticus with and without clinical manifestations and (2) after right hemispherectomy. The cerebral regional oxygen saturation index demonstrated marked fluctuations and progressive decline in both hemispheres during the episodes and normal values in the remaining hemisphere after surgery. We speculate that decreased oxygenation of the nonepileptic cerebral hemisphere in patients with hemimegalencephaly and medically resistant seizures can contribute to the production of global neurologic impairments in these patients and that the benefits of early hemispherectomy are due to the improved oxygenation of the nondysplastic hemisphere following surgery.
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PMID:Bilateral decreased oxygenation during focal status epilepticus in a neonate with hemimegalencephaly. 1522 15

The mechanism underlying the vulnerability of the brain to status epilepticus (SE) induced by pilocarpine remains unknown. Oxidative stress has been implicated in a variety of acute and chronic neurologic conditions, including SE. The present study was aimed at was investigating the changes in catalase activity after pilocarpine-induced seizures and SE. The Control group was treated with 0.9% saline (NaCl, subcutaneously (s.c.)) and sacrificed 1h after the treatment. Another group was treated with pilocarpine (400 mg/kg, s.c., Pilocarpine group) and sacrificed 1h after treatment. The catalase activity in the cerebellum, hippocampus, frontal cortex and striatum of Wistar rats was determined. The results have shown that pilocarpine administration and resulting SE produced a significant increase in the catalase activity in the hippocampus (36%), striatum (31%) and frontal cortex (15%) of treated adult rats. Nevertheless, in the adult rat cerebellum after SE induced by pilocarpine no change was observed in the catalase activity. Our results demonstrated a direct evidence of an increase in the activity of the scavenging enzyme (catalase) in different cerebral structures during seizure activity that could be responsible for eliminating oxygen free radicals and might be one of the compensatory mechanisms to avoid the development of oxidative stress during the establishment of SE induced by pilocarpine. Our reports also indicate clear regional differences in the catalase activity caused by pilocarpine-induced seizures and SE and the hippocampus might be the principal area affected and cerebellum does not modify for this parameter studied during epileptic activity.
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PMID:Catalase activity in cerebellum, hippocampus, frontal cortex and striatum after status epilepticus induced by pilocarpine in Wistar rats. 1524 87

Temporal lobe epilepsy (TLE) is associated with febrile convulsions and childhood status epilepticus (SE). Since the initial precipitating injury, triggering epileptogenesis, occurs during this SE, we aimed to examine the metabolic and morphological cerebral changes during the acute phase of experimental SE noninvasively. In the rat lithium-pilocarpine model of SE, we performed quantified T(2)- and isotropic-diffusion-weighted (DW) magnetic resonance imaging (MRI) at 3 and 5 h of SE and acquired single-voxel (1)H MR spectra at 2, 4 and 6 h of SE. T(2) was globally decreased, most pronounced in the amygdala (Am) and piriformic cortex (Pi), in which also a significant decrease in apparent diffusion coefficient (ADC) was found. In contrast, ADC values increased transiently in the hippocampus (HC) and thalamus (Th). MR spectra showed a decrease in N-acetylaspartate (NAA) and choline (Cho) and an increase of lactate in a hippocampal voxel. The T(2) decrease, attributed to raised deoxyhemoglobin, and the presence of lactate both indicate a mismatch between oxygen demand and delivery. The ADC decrease, indicative of excitotoxicity, confirms that the amygdala and piriformic cortex are particularly vulnerable to lithium-pilocarpine-induced seizures. The transient ADC increase in the thalamus may reflect the breakdown of the blood-brain barrier (BBB), which is shown to occur in this region at these time points. Neuronal damage and failure of energy-dependent formation of NAA are likely causes of an observed decrease in NAA, while the decrease in Cho is possibly due to depletion of the cholinergic system. This study illustrates that relative hypoxia, excitotoxicity and concomitant neuronal damage associated with SE can be probed noninvasively with MR. These pathological phenomena are the first to contribute to the pathophysiology of spontaneous recurrent seizures in a later stage in this animal model.
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PMID:In vivo 1H magnetic resonance spectroscopy, T2-weighted and diffusion-weighted MRI during lithium-pilocarpine-induced status epilepticus in the rat. 1556 33

Propofol (2, 6-diisopropylphenol) is a potent intravenous hypnotic agent which is widely used for the induction and maintenance of anesthesia and for sedation in the intensive care unit. Propofol is an oil at room temperature and insoluble in aqueous solution. Present formulations consists of 1% or 2% (w/v) propofol, 10% soybean oil, 2.25% glycerol, and 1.2% egg phosphatide. Disodium edetate (EDTA) or metabisulfite is added to retard bacterial and fungal growth. Propofol is a global central nervous system depressant. It directly activates GABA(A) receptors. In addition, propofol inhibits the NMDA receptor and modulates calcium influx through slow calcium ion channels. Propofol has a rapid onset of action with a dose-related hypnotic effect. Recovery is rapid even after prolonged use. Propofol decreases cerebral oxygen consumption, reduces intracranial pressure and has potent anti-convulsant properties. It is a potent antioxidant, has anti-inflammatory properties and is a bronchodilator. As a consequence of these properties propofol is being increasingly used in the management of traumatic head injury, status epilepticus, delirium tremens, status asthmaticus and in critically ill septic patients. Propofol has a remarkable safety profile. Dose dependent hypotension is the commonest complication; particularly in volume depleted patients. Hypertriglyceridemia and pancreatitis are uncommon complications. Allergic complications, which may include bronchospasm, have been reported with the formulation containing metabisulfite. In addition, this formulation has been demonstrated to result in the generation of oxygen free radicals. High dose propofol infusions have been associated with the "propofol syndrome"; this is a potentially fatal complication characterized by severe metabolic acidosis and circulatory collapse. This is a rare complication first reported in pediatric patients and believed to be due to decreased transmembrane electrical potential and alteration of electron transport across the inner mitochondrial membrane.
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PMID:Propofol: therapeutic indications and side-effects. 1557 60


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