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)

Epilepsy is one of the most common neurological disorders. Although epilepsy can be idiopathic, it is estimated that up to 50% of all epilepsy cases are initiated by neurological insults and are called acquired epilepsy (AE). AE develops in 3 phases: (1) the injury (central nervous system [CNS] insult), (2) epileptogenesis (latency), and (3) the chronic epileptic (spontaneous recurrent seizure) phases. Status epilepticus (SE), stroke, and traumatic brain injury (TBI) are 3 major examples of common brain injuries that can lead to the development of AE. It is especially important to understand the molecular mechanisms that cause AE because it may lead to innovative strategies to prevent or cure this common condition. Recent studies have offered new insights into the cause of AE and indicate that injury-induced alterations in intracellular calcium concentration levels [Ca(2+)](i) and calcium homeostatic mechanisms play a role in the development and maintenance of AE. The injuries that cause AE are different, but they share a common molecular mechanism for producing brain damage-an increase in extracellular glutamate concentration that causes increased intracellular neuronal calcium, leading to neuronal injury and/or death. Neurons that survive the injury induced by glutamate and are exposed to increased [Ca(2+)](i) are the cellular substrates to develop epilepsy because dead cells do not seize. The neurons that survive injury sustain permanent long-term plasticity changes in [Ca(2+)](i) and calcium homeostatic mechanisms that are permanent and are a prominent feature of the epileptic phenotype. In the last several years, evidence has accumulated indicating that the prolonged alteration in neuronal calcium dynamics plays an important role in the induction and maintenance of the prolonged neuroplasticity changes underlying the epileptic phenotype. Understanding the role of calcium as a second messenger in the induction and maintenance of epilepsy may provide novel insights into therapeutic advances that will prevent and even cure AE.
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PMID:Cellular mechanisms underlying acquired epilepsy: the calcium hypothesis of the induction and maintainance of epilepsy. 1683 74

This study was conducted to characterize the post-pubertal developmental aspects on seizure susceptibility and severity as well as calcium/calmodulin protein kinase type II (CaM kinase II) activity in status epilepticus (SE). Thirty- to ninety-day-old rats, in 10-day increments, were studied. This corresponds to a developmental age group that has not received thorough attention. The pilocarpine model of SE was characterized both behaviorally and electrographically. Seven criteria were analyzed for electrographical characterization: seizure severity, SE susceptibility, the average number of discrete seizures, average time until first seizure, average time to SE, average time from first discrete seizure to SE, and death. After 1 h of SE, specific brain regions were isolated for biochemical study. Phosphate incorporation into a CaM kinase II-specific substrate, autocamtide III, was used to determine kinase activity. There was no developmental effect on the average number of discrete seizures, average time until first seizure, average time to SE, average time from first discrete seizure to SE, and death; however, there was a significant effect on SE probability and seizure severity. Once SE was expressed, all animals showed a decrease in both cortical and hippocampal CaM kinase II activities. Conversely, seizure activity in the absence of SE did not result in a decrease in CaM kinase II activity. The data suggest that there is a gradual age-dependent modulation of SE susceptibility and seizure severity within the developmental stages studied. Additionally, once status epilepticus is observed at any age, there is a corresponding SE-induced inhibition of CaM kinase II.
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PMID:Age dependence of pilocarpine-induced status epilepticus and inhibition of CaM kinase II activity in the rat. 1586 29

We report on an 11-year healthy boy who presented refractory status epilepticus (SE), which was unresponsive to conventional antiepileptic drugs used in the algorithm of the treatment of SE. Based on evidence that verapamil has anticonvulsant activity in animal models and the fact that the boy had a supraventricular tachycardia (140-160 b/min), i.v. verapamil (0.034 mg/min) was administered on day 37, and after a 3.125 mg cumulative verapamil dose (1.5 hour after initiation of the infusion), the patient regained consciousness was able to breathe spontaneously and the electrical SE promptly disappeared. The apparent dramatic response to i.v. verapamil may be explained by its direct anticonvulsant action on the basis of the potential involvement of calcium channels in epileptic activity and that verapamil, a known Pgp inhibitor in the cerebrovascular endothelium in the epilepticus focus, acted by facilitating the brain penetration of the antiepileptic drugs that our patient was receiving simultaneously.
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PMID:Calcium-channel blocker verapamil administration in prolonged and refractory status epilepticus. 1594 42

We examined the mechanism of neuronal necrosis induced by hypoxia in dentate gyrus cultures or by status epilepticus (SE) in adult mice. Our observations showed that hypoxic necrosis can be an active process starting with early mitochondrial swelling and loss of the mitochondrial membrane potential, followed by cytochrome c release and caspase-9-dependent activation of caspase-3. This sequence of events (or program) was independent of protein synthesis and may be induced by energy failure and/or calcium overloading of mitochondria. We called this form of necrosis "programmed necrosis." After SE in adult mice, CA1 and CA3 pyramidal neurons displayed a necrotic morphology, associated with caspase-3 immunoreactivity and with double-stranded DNA breaks, suggesting that "programmed necrosis" may be involved in SE-induced neuronal loss.
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PMID:Programmed neuronal necrosis and status epilepticus. 1598 52

Calcitonin is currently used to treat hypercalcemia of many clinical types. However, we encountered a woman who suffered severe hypercalcemia and status epilepticus, both of which developed 8 days after the administration of salmon calcitonin for the treatment of breast cancer. When the patient first presented her serum calcium level was 15.5mg/dl, intact parathyroid hormone level 118 pg/ml, calcitonin <2 pg/ml, magnesium 1.2mg/dl, and phosphate 1mg/dl. Her serum calcium level returned to the reference range within 48 h after correction. At follow-up no hypercalcemia had developed, although the patient had received no further treatment for her breast cancer and multiple metastases were subsequently detected. Her hypercalcemia is ascribed to exogenous calcitonin supplementation. These conflicting events may be due to functionally heterogeneous calcitonin receptors or to activation of 1 alpha-hydroxylase by exogenous calcitonin.
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PMID:Hypercalcemia and status epilepticus relates to salmon calcitonin administration in breast cancer. 1614 33

Status epilepticus (SE)-induced neuronal death is morphologically necrotic and is initiated by excessive glutamate release, which activates postsynaptic N-methyl-D-aspartate (NMDA) receptors and triggers receptor-mediated calcium influx (excitotoxicity). This results in activation of intracellular proteases and neuronal nitric oxide synthase, with generation of free radicals, and damage to cellular membranes, structural proteins, and essential enzymes. Programmed cell death mechanisms, such as p53 activation, activation of cell death-promoting Bcl-2 family members, and endonuclease-induced DNA laddering, occur in SE-induced neuronal death. Caspase-independent excitotoxic mechanisms, such as NMDA-induced calpain I activation, with activation and translocation of the cell death-promoting Bcl-2 family member Bid from cytoplasm to mitochondria, and subsequent translocation of apoptosis-inducing factor and endonuclease G to nuclei (which cause large-scale and internucleosomal DNA cleavage, respectively), may be triggered by SE. Poly(ADP-ribose) polymerase-1 (PARP-1) activation and cysteinyl cathepsin and DNase II release from lysosomes may occur following SE as well, but these events await future investigation. In the future, rational combinations of central nervous system-penetrable neuroprotective agents, based on our knowledge of excitotoxic mechanisms, may be useful in refractory human SE.
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PMID:Prolonged seizures and cellular injury: understanding the connection. 1627 99

Status epilepticus (SE) can take various forms in idiopathic generalized epilepsy (IGE), some of which forms also occur in symptomatic or focal epilepsies. Although the clinical semiology of the SE episodes may be similar in these different epilepsies, the frequency, response to treatment and prognosis differ. (a) Convulsive SE is surprisingly uncommon in IGE and much less common than in the secondarily generalized or partial epilepsies. Also, when it does occur, it usually responds rapidly to treatment. (b) Typical absence SE occurs only in patients with IGE (the subcategories with typical absence seizures) and also in the syndrome of de novo absence SE of late onset. This form of nonconvulsive SE should be differentiated from atypical absence SE, which occurs in the secondarily generalized epilepsy encephalopathies, and from complex partial SE which occurs in focal epilepsy. The clinical symptoms of these three types overlap but the prognosis and response to treatment are different. The mechanisms underlying absence SE are uncertain and may include both genetic and environmental factors. The termination of absence seizures has been hypothesized to be due to persistent activation of a depolarizing current in thalamocortical neurons that inactivates T-type calcium channels. SE could thus result from dysfunction of this channel or mechanisms that hyperpolarize thalamocortical neurons-these include decreased cortical inhibition, increased reticular thalamic neuronal activity or increased thalamocortical neuron GABA(B)-receptor activation. (c) Generalized electrographic SE is encountered in IGE in the syndrome of phantom absence with GTCS. It also occurs in ESES and in the Landau-Kleffner syndrome. The seizure phenomenology overlaps with the focal SE of temporal or frontal lobe epilepsy. (d) Myoclonic SE is also uncommon in IGE but occurs in juvenile myoclonic epilepsy. It is more commonly encountered in progressive myoclonic epilepsies, myoclonic-astatic epilepsy and in the Dravet syndrome. (e) Autonomic status occurs largely in the Panayiotopoulos syndrome. It is included here under the rubric of IGE, although the epilepsy has focal as well as generalized features and its nosological position is controversial. Fifty percent of seizures in this syndrome could be classified as status epilepticus. There is no doubt that convulsive SE can result in cerebral damage. In animal models of focal SE, nonconvulsive forms can also result in cerebral damage, but cerebral damage is not observed in animal models of absence SE. Similarly, cerebral damage seems not to occur in the forms of nonconvulsive SE in human IGE.
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PMID:Status epilepticus in idiopathic generalized epilepsy. 1782 50

Knock-out (KO) mice lacking gangliotetraose gangliosides attributable to disruption of the gene for GM2/GD2 synthase [GalNAcT (UDP-N-acetylgalactosamine:GM3/GD3 beta-1,4-N-acetylgalactosaminyltransferase; EC 2.4.1.92 [EC])] are revealing key neural functions for the complex gangliosides of brain. This study has found such animals to be highly susceptible to kainic acid (KA)-induced seizures in terms of both seizure severity and duration. Intraperitoneal injection of 25 mg/kg KA produced status epilepticus for approximately 200 min in normal mice or heterozygotes and more than four times longer in the KO mice. The latter group suffered approximately 30% mortality, which increased to approximately 75% at dosage of 30 mg/kg KA, compared with 10-14% for the other two genotypes at the latter dosage. Nissl staining and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling assay revealed substantial deterioration of pyramidal neurons attributable to apoptosis in the KO hippocampus, especially the CA3 region. Seizure activity in the KO mouse was only moderately diminished by intraperitoneal injection of GM1 ganglioside, whereas LIGA 20, a semisynthetic analog of GM1, substantially reduced both seizure severity and cell damage. The potency of LIGA 20 was correlated with its enhanced membrane permeability (compared with GM1), as seen in the increased uptake of [3H]LIGA 20 into the subcellular fractions of brain including cell nuclei. The latter finding is consonant with LIGA 20-induced restoration of the Na+/Ca2+ exchanger located at the inner membrane of the nuclear envelope in KO mice, an exchanger dependent on tight association with GM1 or its analog for optimal activity. These results point to a neuroprotective role for GM1 and its associated exchanger in the nucleus, based on regulation of Ca2+ flux between nucleoplasm and nuclear envelope.
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PMID:Enhanced susceptibility to kainate-induced seizures, neuronal apoptosis, and death in mice lacking gangliotetraose gangliosides: protection with LIGA 20, a membrane-permeant analog of GM1. 1630 14

A PubMed search of the years 1965 to 2003 found only 30 articles that were directly related to modeling seizures or epilepsy in aged animals. This lack of research is disturbing but explainable because of the high cost of aged animals and their increasing infirmity. Many changes occur in the older brain: cell loss in the hippocampal formation, changes in long-term potentiation maintenance, alteration in kindling, increased susceptibility to status epilepticus, and neuronal damage from stroke. The effect of aging on voltage-gated sodium and calcium channels has not been studied sufficiently. With increasing numbers of elderly persons with epilepsy needing appropriate treatment, the need to better understand the basic mechanisms of epilepsy is crucial.
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PMID:Basic research in epilepsy and aging. 1638 87

Recurrent mossy fiber synapses in the dentate gyrus of epileptic brain facilitate the synchronous firing of granule cells and may promote seizure propagation. Mossy fiber terminals contain and release zinc. Released zinc inhibits the activation of NMDA receptors and may therefore oppose the development of granule cell epileptiform activity. Hippocampal slices from rats that had experienced pilocarpine-induced status epilepticus and developed a recurrent mossy fiber pathway were used to investigate this possibility. Actions of released zinc were inferred from the effects of chelation with 1 mM calcium disodium EDTA (CaEDTA). When granule cell population bursts were evoked by mossy fiber stimulation in the presence of 6 mM K(+) and 30 microM bicuculline, CaEDTA slowed the rate at which evoked bursting developed, but did not change the magnitude of the bursts once they had developed fully. The effects of CaEDTA were then studied on the pharmacologically isolated NMDA receptor- and AMPA/kainate receptor-mediated components of the fully developed bursts. CaEDTA increased the magnitude of NMDA receptor-mediated bursts and reduced the magnitude of AMPA/kainate receptor-mediated bursts. CaEDTA did not affect the granule cell bursts evoked in slices from untreated rats by stimulating the perforant path in the presence of bicuculline and 6 mM K(+). These results suggest that zinc released from the recurrent mossy fibers serves mainly to facilitate the recruitment of dentate granule cells into population bursts.
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PMID:Facilitation of granule cell epileptiform activity by mossy fiber-released zinc in the pilocarpine model of temporal lobe epilepsy. 1649 Jan 81


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