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)

EEG registered hippocampal status epilepticus (HSE) was provoked in 41 adult albino rats by intraseptal injection of ouabain, and the hippocampus was studied from 1 1/2 to 24 hr with the enzyme histochemical tests for succinic dehydrogenase (SDH), lactic dehydrogenase (LDH), thiaminopyrophosphatase (TPPase), acid phosphatase (AcPase), Mg2+ adenosine triphosphatase (Mg2++ ATPase), and with general and neurohistological stains. In a first group of animals (1 1/2 to 10 hr of HSE), a stage of general increase in enzymatic activity was detected in the pyramidal neurons (SDH, LDH, AcPase, and TPPase). Mg2+ ATPase showed a marked increase in astrocytes. In a second group (more than 10 hr of HSE), SDH was found decreased in the dendritic fields. LDH activity persisted in neuronal bodies, and AcPase and TPPase showed diffuse activity in the cytoplasm of some pyramidal neurons. In a third group (more than 18 hr of HSE), SDH activity was low. No AcPase granules were observed in some pyramidal neurons and TPPase was negative in some areas of pyramidal layer. Mg2+ ATPase reaction showed scare and retracted astroglial processes. These changes were coincident with "cellular ghosts" observed with hematoxylin-eosin techniques of the same samples in the pyramidal field and were interpreted as cellular death, attributed to relative anoxia following neuronal discharge.
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PMID:Enzyme histochemistry of the rat hippocampus during experimental status epilepticus. 15 26

The use of magnesium sulfate (MgSO4) as an anticonvulsant is controversial. Status epilepticus was induced in 0.5% halothane-anesthetized Wistar rats with a threshold (90 mg/kg) or suprathreshold (200 mg/kg) dose of intravenous (i.v.) pentylenetetrazol (PTZ) under stereotactic hippocampal depth electrode monitoring. Fifteen minutes after seizure induction, the maximum hemodynamically tolerated dose of MgSO4 (10 mg/kg/min in 22 min) was administered i.v. MgSO4 was ineffective in altering seizure discharge. A subgroup of nine animals received hypertonic mannitol before MgSO4 to open the blood-brain barrier (BBB) to facilitate Mg2+ CNS penetration. Again MgSO4 was ineffective in attenuating epileptic activity. These results support the contention that MgSO4 is not an effective treatment for status epilepticus. We hypothesize that because Mg2+ blocks Ca2+ influx into the neuron through the N-methyl-D-aspartate (NMDA) receptor-operated calcium channel in a voltage-dependent manner it would be ineffective in neurons that are continuously depolarizing as in status epilepticus.
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PMID:Effects of magnesium sulfate on pentylenetetrazol-induced status epilepticus. 183 Nov 20

Lowering of extracellular Mg2+ results in various forms of epileptiform activity in different parts of temporal lobe slices [5,22] which contain neocortical areas such as areas Te2 or Te3, the entorhinal cortex (EC), subiculum, hippocampal areas CA1 to CA3 and the dentate gyrus [5,11]. In the EC, the subiculum and Te2/Te3 seizure-like events (SLEs) with tonic and clonic electrographic discharge patterns, negative slow field potentials and ionic changes comparable to those during tonic-clonic seizures in intact animals were observed. After 30 to 120 min of recurrent seizure activity (80 +/- 37 min) the seizure-like events (SLEs) developed into a state of late recurrent discharges (LRDs). Since previous studies had shown that the LRDs do not respond to valproic acid in contrast to a blocking effect of this drug on SLEs, we investigated the effects of the clinically employed anticonvulsants phenytoin, carbamazepine, phenobarbital, midazolam and ethosuximide on LRDs. All these agents were unable to block the LRDs in the EC, subiculum and Te2/Te3. This was found true both for concentrations which can block SLEs and for higher concentrations. Thus we conclude that this activity may represent a model of difficult to treat status epilepticus.
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PMID:Paroxysmal epileptiform discharges in temporal lobe slices after prolonged exposure to low magnesium are resistant to clinically used anticonvulsants. 775 May 6

Glutamate is an excitatory neurotransmitter in the mammalian central nervous system and a neurotoxin (excitotoxin) that has the potential to destroy neurones by activation of ionotropic receptors. In contrast to the well documented role of glutamate in the pathogenesis of neuronal degeneration resulting from hypoxia/ischaemia, hypoglycaemia, status epilepticus and trauma, it has been difficult to establish a link between the excitotoxicity and neuronal death that occur in chronic neurodegenerative disorders. Impairment of energy metabolism has been shown to increase neuronal vulnerability to glutamate. The cause of this phenomenon lies in the attenuation of the Mg2+ blockade of the N-methyl-D-aspartate receptors that leads to persistent activation of these receptors by physiologic extracellular glutamate concentrations. The concept of increased neuronal vulnerability to excitotoxic injury establishes a link between slow neuronal degeneration and excitotoxicity and suggests that glutamate antagonists may prove beneficial in the treatment of chronic neurodegenerative diseases that have been resistant to therapy.
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PMID:Excitotoxicity and neurodegenerative diseases. 884 37

Propofol (2,6 di-isopropylphenol) is an intravenous general anesthetic used widely in neuroanesthesia, as a sedative in intensive care units, and has successfully aborted refractory status epilepticus. We investigated the effects of propofol on epileptiform activity in rat hippocampal slices. Interictal epileptiform activity was produced by bath applying one of the following: picrotoxin (PTX; 10 and 50 microM), bicucculine methiodide (BMI; 10 and 50 microM), 4-aminopyridine (4-AP; 50 microM), 8.5 mM [K+]o or 0 [Mg2+]o artificial cerebrospinal fluid. Propofol was then added in increasing concentrations and the effect on the rate of extracellular field epileptiform discharges was measured. Ictal-like discharges (> 2 Hz for > 2 s) were produced by 7.5 mM [K+]o and pilocarpine (10 microM). Propofol (30 micrograms/ml, 168 microM) completely abolished discharges induced by 8.5 mM [K+]o and at 60 micrograms/ml (337 mM) completely suppressed discharges induced by 4-AP and 0 [Mg2+]o. Propofol was less effective in reducing discharges produced by GABAA/Cl- receptor complex antagonists. Propofol at a concentration of 300 micrograms/ml (1.7 mM) was needed to reduce BMI-induced (50 microM) discharges by 77% and only reduced PTX-induced (50 microM) discharges by 20%. Ictal-like discharges produced by pilocarpine were disrupted by low concentrations of propofol (3-10 micrograms/ml, 16.9-56.2 microM) and the duration of the ictal-like discharge period was significantly reduced. We found that propofol has significant in vitro antiepileptic effects. Additionally, propofol was less effective against GABAA antagonists suggesting that the GABAA receptor complex is the site of its action.
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PMID:Propofol inhibits epileptiform activity in rat hippocampal slices. 895 13

The mechanisms by which neurons die after stroke and status epilepticus and related neuropathological conditions are unclear, but may involve voltage-dependent Na+ channels, glutamate receptors, and nitric oxide (NO.). These questions were investigated using an in vitro primary cell culture model in which hippocampal pyramidal neurons undergo a gradual and delayed neurodegeneration induced by enhanced excitatory neurotransmission. When cells were treated with Mg2+-free, glycine-supplemented medium for a brief period (15 min) and examined 24 h later, approximately 30-40% of the neurons had died. Cell death could be inhibited by blockers of voltage-sensitive Na+ channels and by N-methyl-D-aspartate receptor antagonists. Application of either the endogenous antioxidant melatonin (EC50: 19.2+/-2.8 microM) or the NO. synthase inhibitor Nomega-nitro-L-arginine after, but not during, Mg2+-free exposure protected against delayed neuronal death; significant neuroprotection was observed when the addition was delayed for up to 4 h. This operational time window suggests that an enduring production of NO. and reactive oxygen species from neuronal sources is responsible for delayed cell death. A role for reactive oxygen species in this injury process was strengthened by the finding that, whereas neurons cocultured with astroglia were more resistant to killing, agents capable of lowering intracellular glutathione negated this protection. Because secretion levels of melatonin are decreased with aging, reductions in this pineal hormone may place neurons at a heightened risk for damage by excitatory synaptic transmission.
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PMID:Melatonin prevents the delayed death of hippocampal neurons induced by enhanced excitatory neurotransmission and the nitridergic pathway. 961 51

During seizure-like events (SLEs), intracellular Ca2+ concentration ([Ca2+]i) increases causing depolarization of the mitochondrial membrane and subsequent intramitochondrial accumulation of Ca2+. Mitochondrial depolarization results in an interruption of oxidative phosphorylation and increase in reactive oxygen species. Calcium activates enzymes of the citrate cycle. A characteristic feature of the low-Mg2+-induced SLEs is that they are transformed to a late activity refractory to anticonvulsant drugs, which may be regarded as a model system of difficult to treat status epilepticus. In contrast, 4-aminopyridine (4-AP)-induced activity rarely evolves to such late activity. The autofluorescence of NAD(P)H was used to monitor changes in cellular energy metabolism in the entorhinal cortex in two in vitro models of focal epilepsy. During repetitive 4-AP-induced SLEs there was a short decrease followed by a long-lasting overshoot of the NAD(P)H signal. This sequence remained unaltered during recurring SLEs. In contrast, during recurrent low-Mg2+-induced SLEs, the brief initial NADH signal reduction was unchanged but the following overshoot of NADH displayed a continuous decrease. This indicates a relative energy failure, which may contribute to the transformation to late activity in the low-Mg2+ model.
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PMID:A relative energy failure is associated with low-Mg2+ but not with 4-aminopyridine induced seizure-like events in entorhinal cortex. 991

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

Epilepsy or the occurrence of spontaneous recurrent epileptiform discharges (SREDs, seizures) is one of the most common neurological disorders. Shift in the balance of brain between excitatory and inhibitory functions due to different types of structural or functional alterations may cause epileptiform discharges. N-Methyl-D-aspartate (NMDA) receptor dysfunctions have been implicated in modulating seizure activities. Seizures and epilepsy are clearly dependent on elevated intracellular calcium concentration ([Ca2+]i) by NMDA receptor activation and can be prevented by NMDA antagonists. This perturbed [Ca2+]i levels is forerunner of neuronal death. However, therapeutic tools of elevated [Ca2+]i level during status epilepticus (SE) and SREDs have not been discovered yet. Our previous study showed fast inhibition of ginseng total saponins and ginsenoside Rg3 on NMDA receptor-mediated [Ca2+]i in cultured hippocampal neurons. We, therefore, examined the direct modulation of ginseng on hippocampal neuronal culture model of epilepsy using fura-2-based digital Ca2+ imaging and neuronal viability assays. We found that ginseng total saponins and ginsenoside Rg3 inhibited Mg2+ free-induced increase of [Ca2+]i and spontaneous [Ca2+]i oscillations in cultured rat hippocampal neurons. These results suggest that ginseng may play a neuroprotective role in perturbed homeostasis of [Ca2+]i and neuronal cell death via the inhibition of NMDA receptor-induced SE or SREDs.
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PMID:Ginsenosides inhibit NMDA receptor-mediated epileptic discharges in cultured hippocampal neurons. 1520 58

Cannabinoids have been shown to have anticonvulsant properties, but no studies have evaluated the effects of cannabinoids in the hippocampal neuronal culture models of acquired epilepsy (AE) and status epilepticus (SE). This study investigated the anticonvulsant properties of the cannabinoid receptor agonist R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolol[1,2,3 de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone (WIN 55,212-2) in primary hippocampal neuronal culture models of both AE and SE. WIN 55,212-2 produced dose-dependent anticonvulsant effects against both spontaneous recurrent epileptiform discharges (SRED) (EC50 = 0.85 microM) and SE (EC50 = 1.51 microM), with total suppression of seizure activity at 3 microM and of SE activity at 5 microM. The anticonvulsant properties of WIN 55,212-2 in these preparations were both stereospecific and blocked by the cannabinoid type-1 (CB1) receptor antagonist N-(piperidin-1-yl-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A; 1 microM), showing a CB1 receptor-dependent pathway. The inhibitory effect of WIN 55,212-2 against low Mg2+-induced SE is the first observation in this model of total suppression of SE by a selective pharmacological agent. The clinically used anticonvulsants phenytoin and phenobarbital were not able to abolish low Mg2+-induced SE at concentrations up to 150 microM. The results from this study show CB1 receptor-mediated anticonvulsant effects of the cannabimimetic WIN 55,212-2 against both SRED and low Mg2+-induced SE in primary hippocampal neuronal cultures and show that these in vitro models of AE and SE may represent powerful tools to investigate the molecular mechanisms mediating the effects of cannabinoids on neuronal excitability.
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PMID:Activation of the cannabinoid type-1 receptor mediates the anticonvulsant properties of cannabinoids in the hippocampal neuronal culture models of acquired epilepsy and status epilepticus. 1646 64


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