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)

This study was performed to determine the effect of prolonged status epilepticus on the activity and subcellular location of a neuronally enriched, calcium-regulated enzyme, calcineurin. Brain fractions isolated from control animals and rats subjected to pilocarpine-induced status epilepticus were subjected to differential centrifugation. Specific subcellular fractions were tested for both calcineurin activity and enzyme content. Significant, status epilepticus-induced increases in calcineurin activity were found in homogenates, nuclear fractions, and crude synaptic membrane-enriched fractions isolated from both cortex and hippocampus. Additionally, significant increases in enzyme levels were observed in crude synaptic fractions as measured by Western analysis. Immunohistochemical studies revealed a status epilepticus-induced increase in calcineurin immunoreactivity in dendritic structures of pyramidal neurons of the hippocampus. The data demonstrate a status epilepticus-induced increase in calcineurin activity and concentration in the postsynaptic region of forebrain pyramidal neurons.
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PMID:Status epilepticus-induced changes in the subcellular distribution and activity of calcineurin in rat forebrain. 1467 64

Young adult and aged male Fisher 344 rats underwent kainate-induced convulsive status epilepticus (SE) for 4 h prior to sacrifice to determine potential aging-related differences in the effect of prolonged SE on the expression of hippocampal voltage-gated calcium channels (VGCCs). Immunohistochemistry was performed on hippocampal sections using antibodies directed against the alpha1 subunit of class A-D VGCCs. Compared to age-matched controls, SE animals showed a marked loss of alpha1A immunoreactivity (IR) in CA3 and the hilus, which was more prominent in aged animals. Alpha1B-IR was decreased selectively in the stratum lucidum of CA3. Alpha1C-IR was increased on neuronal somata in the pyramidal and granule cell layers of both age groups. In contrast, there was a marked decrease of alpha1C-IR in the neuropil of CA3 stratum pyramidale and portions of CA1, which was more pronounced in aged animals. Alpha1D-IR was decreased in CA3 and the hilus, which was more prominent in aged animals. Nissl staining demonstrated mild somal dysmorphia in the pyramidal cell layer of CA3, which was more apparent in aged animals. Fluoro-Jade B staining was prominent in the stratum pyramidale of CA3 and in the hilus of aged SE animals. These results demonstrated that expression patterns of hippocampal high-threshold VGCC alpha1 subunits were altered variably during prolonged convulsive SE and were associated with prominent early degenerative changes in aged neurons in CA3 and the hilus.
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PMID:Alterations in hippocampal voltage-gated calcium channel alpha 1 subunit expression patterns after kainate-induced status epilepticus in aging rats. 1470 30

The ideal antiepileptic drug (AED) should correct the aberrant pathophysiology of epileptogenesis without interfering with normal neurotransmission A new group of drugs with antiepileptic efficacy, without sedative properties, would be an exciting prospect. Theoretical considerations and results from experimental animal models of epilepsy have put forward the possibility that calcium (Ca2+) antagonists may form such a group. The initiation of epileptogenic activity in the neuron is thought to be connected with the phenomenon known as "intrinsic burst firing", which is activated by an inward Ca2+ current. Ca2+ is described as the primary mediator of "excitotoxic" neuronal damage. Both necrotic and apoptotic cell death is associated with Ca2+ entry into the cells during status epilepticus. The Ca2+ channel blockers depressed epileptic depolarizations of neurons. In this review, we present anticonvulsant effects of cinnarizine, flunarizine, nifedipine, nimodipine, nicardipine, amlodipine, isradipine, niguldipine, diltiazem, verapamil and dantrolene in animal models of seizures. Also, a detailed analysis of interactions between Ca2+ blockers and AEDs was performed. Clinical trials in intractable epilepsy support to a certain degree antiepileptic properties of Ca2+ antagonists.
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PMID:Calcium modulation in epilepsy. 1504 75

Antiepileptic drugs (AEDs) are designed to prevent and suppress seizure activity. Their effects on calcium influx and molecular cascades contributing to necrotic and apoptotic neuronal death, however, suggests that they have functions other than just suppression of excitability. The neuroprotective effects of 20 AEDs currently in use or being investigated in Phase II - III clinical trials for treatment of epilepsy are reviewed. Data analyses is complicated by several factors. Firstly, the available data on the neuroprotective effects of different AEDs varies largely. Secondly, most of the evidence demonstrating neuroprotective effects comes from stroke models and it is uncertain whether these data can be extrapolated to other conditions, such as status epilepticus (SE) or traumatic brain injury. Thirdly, data obtained in adult animals cannot be extrapolated to young animals without caution. For example, AEDs protecting adult brain from stroke or SE-induced injury can cause apoptosis in immature brain. Finally, data comparison is complicated by the variability in study designs and methodologies between studies. With these caveats in mind, an analysis of the available data suggests that AEDs with different mechanisms of action can have mild-to-moderate neuroprotective effects. It is difficult, however, to associate the neuroprotective effects with a favourable functional outcome. For example, it is difficult to conclude that administration of AEDs during the latency phase would have an effect on the molecular cascades underlying epileptogenesis. The few favourable data demonstrating a decrease in the incidence of epilepsy after SE are probably related to the administration of AEDs during SE, which resulted in modification/alleviation of the insult itself and consequently, reduced its epileptogenecity. These experimental data, however, are clinically important because they show that early intervention of SE has an effect on long-term functional outcome. These observations emphasise the need to use additional outcome measures, such as markers of normal development or cognitive performance, when the benefits of neuroprotection achieved by the use of neuroprotective AEDs are assessed.
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PMID:Antiepileptic drugs in neuroprotection. 1510 63

Immunocytochemical markers of specific rat hippocampal interneuron subpopulations, including the calcium binding proteins parvalbumin (PV), and calretinin (CR) were examined in relation to the evolution of spontaneous seizures after electrically induced status epilepticus (SE). PV/CR/NeuN immunoreactive neurons were counted in the hippocampal formation at different time intervals after SE and related to spontaneous hippocampal discharge activity. Decreased PV immunoreactivity was observed within 1 day after SE in the hilus, pre- and parasubiculum, and in the entorhinal cortex layers II and V/VI. In layer III, the density of detectable PV immunoreactive neurons did not decrease significantly, whereas the number of surrounding principal neurons was extensively decreased within a week in most post-SE rats, and after 3-4.5 months in all rats that had developed a progressive evolution of seizures. CR immunoreactive neuron number decreased in all hippocampal subregions except for the stratum lacunosum-moleculare and the EC layer II, in which the density did not decrease significantly. The apparent decrease in the number of PV and CR immunoreactive hilar neurons was correlated with the duration of the SE and was most extensive in rats with a progressive form of epilepsy. The loss of CR and PV expression or the loss of CR- and PV-containing neurons in specific regions of the hippocampal formation may play a role in the progressive nature of epilepsy possibly via increasing the entorhinal-hippocampal activity.
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PMID:Progression of temporal lobe epilepsy in the rat is associated with immunocytochemical changes in inhibitory interneurons in specific regions of the hippocampal formation. 1514 63

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

Four noninstitutionalized patients, 4 months - 51 years old, presented out of 421 patients with epilepsy seen within a period of 2 years with serious symptoms of vitamin D deficiency secondary to chronic antiepileptic drug therapy. Presenting symptoms included exacerbation of seizure activity, status epilepticus, carpopedal spasms, fractures, osteomalacia, and rickets. All had low serum calcium and low vitamin D levels. Our experience supports the practice of screening patients on chronic antiepileptic drug therapy for vitamin D abnormalities.
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PMID:Symptomatic antiepileptic drug associated vitamin D deficiency in noninstitutionalized patients: an under-diagnosed disorder. 1529 60

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

Alterations in hippocampal neuronal Ca(2+) and Ca(2+)-dependent systems have been implicated in mediating some of the long-term neuroplasticity changes associated with acquired epilepsy (AE). However, there are no studies in an animal model of AE that directly evaluate alterations in intracellular calcium concentration ([Ca(2+)](i)) and Ca(2+) homeostatic mechanisms (Ca(2+) dynamics) during the development of AE. In this study, Ca(2+) dynamics were evaluated in acutely isolated rat CA1 hippocampal, frontal, and occipital neurons in the pilocarpine model by using [Ca(2+)](i) imaging fluorescence microscopy during the injury (acute), epileptogenesis (latency), and chronic-epilepsy phases of the development of AE. Immediately after status epilepticus (SE), hippocampal neurons, but not frontal and occipital neurons, had significantly elevated [Ca(2+)](i) compared with saline-injected control animals. Hippocampal neuronal [Ca(2+)](i) remained markedly elevated during epileptogenesis and was still elevated indefinitely in the chronic-epilepsy phase but was not elevated in SE animals that did not develop AE. Inhibiting the increase in [Ca(2+)](i) during SE with the NMDA channel inhibitor MK801 was associated in all three phases of AE with inhibition of the changes in Ca(2+) dynamics and the development of AE. Ca(2+) homeostatic mechanisms in hippocampal neurons also were altered in the brain-injury, epileptogenesis, and chronic-epilepsy phases of AE. These results provide evidence that [Ca(2+)](i) and Ca(2+)-homeostatic mechanisms are significantly altered during the development of AE and suggest that altered Ca(2+) dynamics may play a role in the induction and maintenance of AE and underlie some of the neuroplasticity changes associated with the epileptic phenotype.
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PMID:Evidence that injury-induced changes in hippocampal neuronal calcium dynamics during epileptogenesis cause acquired epilepsy. 1558 36

Overactivation of N-methyl-D-aspartate receptors is known to mediate excitotoxicity due to excessive entry of calcium, leading to the activation of several calcium-dependent enzymes. Calpains are calcium-activated proteases that appear to play a role in excitotoxic neuronal death. Several cellular proteins are substrates for these proteases, particularly the N-methyl-D-aspartate receptor. Recently, cleavage of NR2B subunits has been implicated in excitotoxic neurodegeneration in ischemia. In this work, we investigated the proteolysis by calpains of NR2B subunits of the N-methyl-D-aspartate receptor in the hippocampus of epileptic rats. Our results show that cleaved forms of NR2B subunits are formed after status epilepticus, in the same areas of the hippocampus where calpain activation was detected by immunohistochemical staining of calpain-specific spectrin breakdown products.
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PMID:Proteolysis of NR2B by calpain in the hippocampus of epileptic rats. 1572 44


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