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)

The pro- or anticonvulsant properties of propofol remain a matter of controversy. Although numerous case reports describe the appearance of abnormal movements, posturing and seizure-like activity related to the use of propofol, systematic studies in both humans and animals strongly suggest that it possesses antiepileptic properties. Propofol consistently reduces the seizure duration during electroconvulsive therapy, its use has been successful in controlling refractory status epilepticus and in animals it offers a strong protection against lignocaine- or pentylene-tetrazol-induced epilepsy. The beneficial effects of propofol may be related to its uniform depressant action on the central nervous system, to a potentialization of GABA-mediated pre- and postsynaptic inhibition, and by decreasing the release of excitatory transmitters, glutamate and aspartate.
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PMID:Propofol: pro- or anticonvulsant? 920 33

Intracellular recording techniques were used to examine GABA(A) receptor-mediated synaptic inhibition in pyramidal cells of the CA1 region of the rat hippocampus in the post-self sustaining limbic status epilepticus model of temporal lobe epilepsy. Orthodromically evoked, monosynaptic inhibitory postsynaptic potentials were recorded in vitro following pharmacological blockade of ionotropic glutamate and GABA(B) receptors. Inhibitory postsynaptic potentials from epileptic tissue were kinetically altered relative to controls; both the 10-90% rise-time and width (measured at half-maximum amplitude) were reduced by approximately 50% resulting in significant shortening of duration. The degree of pyramidal cell hyperexcitability, assessed before pharmacological treatment as the number of action potentials evoked by maximum intensity afferent stimulation, correlated significantly with the magnitude of synaptic potential duration reduction determined following blockade of glutamatergic neurotransmission. Bath application of the benzodiazepine type 1 receptor agonist zolpidem reduced post-self sustaining limbic status epilepticus CA1 pyramidal cell hyperexcitability substantially (but not completely) via a marked increase in inhibitory postsynaptic potential area. Post-self-sustaining limbic status epilepticus inhibitory postsynaptic potentials which exhibited the most pronounced shortening were augmented by zolpidem to a greater degree than longer duration synaptic potentials. In contrast, zolpidem-induced augmentation of control inhibitor, postsynaptic potential area was much less robust. It is suggested that a deficiency in post-self-sustaining limbic status epilepticus GABA(A) receptor-mediated synaptic inhibition contributes to a state of partial disinhibition which is a major factor in enhanced CA1 excitability in chronic limbic epilepsy. Possible mechanisms underlying post-self-sustaining limbic status epilepticus kinetic abnormalities are discussed.
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PMID:Shortened-duration GABA(A) receptor-mediated synaptic potentials underlie enhanced CA1 excitability in a chronic model of temporal lobe epilepsy. 928 63

Fast synaptic inhibition in the forebrain is mediated primarily by GABA acting on GABAA receptors (GABARs). GABARs are regulated by numerous positive (barbiturates, benzodiazepines, and neurosteroids) and negative (picrotoxin, bicuculline, and Zn2+) allosteric modulators. The sensitivity of GABARs to GABA and to allosteric modulators changes gradually during normal development, during development of chronic epilepsy, and after prolonged exposure to GABAR agonists. Here we report the development of rapid functional plasticity of GABARs occurring over 45 min of continuous seizures (status epilepticus) in rats. Seizures induced in rats by administration of lithium followed by pilocarpine were readily terminated by the benzodiazepine diazepam when administered early during the seizures (after 10 min of seizures). However, during status epilepticus, there was a substantial reduction of diazepam potency for termination of the seizures. To determine whether the loss of sensitivity of the animals to diazepam was caused by an alteration of GABAR functional properties, we obtained whole-cell GABAR currents from hippocampal dentate granule cells isolated acutely from control rats and from rats undergoing status epilepticus. GABAR properties were characterized by determining GABA sensitivity and the sensitivity of GABARs to regulation by benzodiazepines, barbiturates, and Zn2+. When compared with those from naive controls, GABAR currents from rats undergoing status epilepticus were less sensitive to diazepam and Zn2+ but retained their sensitivity to GABA and pentobarbital. We conclude that the prolonged seizures of status epilepticus rapidly altered the functional properties of hippocampal dentate granule cell GABARs.
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PMID:Rapid seizure-induced reduction of benzodiazepine and Zn2+ sensitivity of hippocampal dentate granule cell GABAA receptors. 929 98

The effects of the administration of two doses (1,000 and 1,500 mg kg-1) of gamma-vinyl-GABA (GVG), have been tested in pubescent rats, systemically injected with kainic acid (KA). The changes in spontaneous behaviour before KA injection, the behavioural and epileptic manifestations (Wet Dog Shakes, Limbic Seizures and Status Epilepticus) and the lethality rate caused by KA were taken into account and compared to those observed in controls and in carbamazepine (CBZ) or phenytoin (PHT) treated animals. While GVG appeared to reduce the incidence of the epileptic manifestations and the subsequent mortality, particularly when higher doses of the drug were used, CBZ exerted a proconvulsant action and PHT did not substantially modify the parameters considered. Moreover, GVG, but not CBZ and PHT, induced remarkable sedative effects which disappeared within 48 h. The different anticonvulsant profile of GVG, CBZ and PHT were correlated to their different modes of action, since GVG acts by enhancing the inhibitory GABA-mediated processes, while CBZ and PHT act by reducing the excitatory processes.
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PMID:Vigabatrin versus carbamazepine and phenytoin in kainic acid-treated pubescent rats. 934 35

In adult rats, kainic acid-induced status epilepticus markedly reduces GluR2 (the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid, AMPA subunit that limits Ca2+ permeability), receptor mRNA in the vulnerable CA3 and may contribute to delayed neurodegeneration. In rat pups resistant to kainate seizure-induced hippocampal neurodegeneration by silver impregnation, glutamate or GABA(A) alpha1-receptor mRNAs were unaltered in CA3 neurons 24 h after status epilepticus. In the dentate gyrus, GluR1 and GluR2 mRNAs were transiently increased in P14 but not P5 pups. Immunocytochemistry revealed no apparent differences in the distribution patterns of GluR1, GluR2, or GluR2/3 receptor proteins in the CA3 or dentate gyrus of P14 pups. Status epilepticus-induced alterations in receptor GluR2 and GABA(A) alphal mRNAs and AMPA protein expression vary with developmental age. Sustained expression at young ages may contribute to the resistance of developing hippocampal neurons to seizure-induced damage.
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PMID:Developmental regulation of glutamate and GABA(A) receptor gene expression in rat hippocampus following kainate-induced status epilepticus. 944 90

Status epilepticus (prolonged or repetitive seizures without a period of recovery between them) is a life-threatening medical emergency for which appropriate diagnosis and treatment are imperative. It is usually classified with a practical aim as convulsive and non-convulsive, generalized and partial. In convulsive status there is a critical period of 30 min before irreversible metabolic alterations appear. The factors that influence the beginning and endpoint of a status epilepticus are unknown but a role has been proposed for both glutamate mediates excitation and lack of GABA mediated inhibition.
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PMID:[Concept, classification and pathophysiology of status epilepticus]. 947 Apr 31

The pool of zinc present in excitatory synaptic terminals in normal and pathological conditions (for instance the status epilepticus induced by kainic acid) can be stained by a silver sulphide method followed by physical development of the insoluble zinc-sulphide complexes. In this study we applied a previously described simple and rapid developing procedure that reveals synaptic zinc, to the study of normal and pathological hippocampi and combined it with pre and postembedding immunocytochemical methods to detect different antigens. Normal and kainic acid-treated rats were perfused with fixative solutions containing sodium sulphide and 50 microm-thick vibratome sections of the hippocampi were incubated in a commercial developing solution (IntenSE M, Amersham). The developed vibratome sections were then (1) mounted for light microscopy or osmicated and epon-embedded for electron microscopy; or (2) processed for the preembedding immunoenzymatic detection of various antigens (GABA, parvalbumin, calbindin) with light and electron microscopy. Thin sections from epon-embedded samples were also processed for the postembedding immunogold localization of glutamate. This very simple and rapid procedure gives rise to zinc-specific staining, comparable to that obtained with classical developing methods and good preservation of both antigenicity and ultrastructure. It is therefore possible to detect, in the same thick or thin section, zinc reaction product and different antigens.
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PMID:A simplified procedure for the physical development of the sulphide silver method to reveal synaptic zinc in combination with immunocytochemistry at light and electron microscopy. 953 64

In the limbic status model of chronic temporal lobe epilepsy, hippocampal stimulation induces acute status epilepticus in rats; recurrent, spontaneous seizures develop following an asymptomatic silent period lasting several weeks. Previous work has shown increased excitability and decreased inhibition in CA1 pyramidal neurons in chronically epileptic animals. To determine the relationship of altered cellular responses to seizure onset, in vitro intracellular recording was used to follow the evolution of changes in synaptic physiology occurring during the seizure-free silent period. Pyramidal cells displayed increasing epileptiform activity throughout the period investigated, 3-14 days following status; the mean number of evoked action potentials from 1.1+/-0.05 in control cells to 2.4+/-0.4 early (3 days after status) and 4. 3+/-0.7 late (14 days) in the silent period. Monosynaptic inhibitory postsynaptic potentials mediated by gamma-aminobutyric acid-A receptors in silent period cells differed markedly from controls. Area, rise time, and duration of these potentials decreased by 40-60% within 3 days following status and to values commensurate with chronically epileptic animals in 7 to 10 days. gamma-Aminobutyric acid-B receptor-mediated IPSPs diminished more gradually in the silent period, reaching a minimum at day 14. In contrast, presynaptic gamma-aminobutyric acid-B receptor function showed maximum impairment 3 days after status. The benzodiazepine type 1 receptor agonist zolpidem reduced hyperexcitability in both silent period and chronically epileptic cells, but was more effective at unmasking the underlying IPSP in silent period neurons. The results indicate that changes in different components of pyramidal cell inhibitory synaptic physiology associated with chronic epilepsy in this model evolve individually at different rates, but are all complete before seizure onset. Although the results do not imply causality, they do suggest that the development of physiological changes in CA1 pyramidal cells may contribute to the lag period preceding the onset of chronic seizures.
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PMID:Ontogeny of altered synaptic function in a rat model of chronic temporal lobe epilepsy. 967 75

The atypical antipsychotic clozapine treatment (at high doses) has been reported to be associated with tremors. However, antitremor effects of clozapine have also been reported in Parkinsonian patients. Recently, we reported the protective effects of acute clozapine against pilocarpine-induced status epilepticus (SE). With this background, this study was designed to investigate the possible protective effect of clozapine against acute chemoconvulsions and kindling seizures produced by pentylenetetrazol (PTZ) in mice. Various doses of clozapine (1.0, 2.5, 5.0 and 7.5 mg) offered different degrees of protective effects against PTZ (80 mg) challenge, and the maximum protection was observed with the 2.5 mg dose as it delayed the onset of jerks, clonus, tonic extensor phase and reduced mortality. Animals chronically pretreated with clozapine (2.5, 7.5 and 15.0 mg) for 8 days when challenged by PTZ (50 and 80 mg) on the 8th day also showed protection. Repeated administration of PTZ at a subconvulsive dose (30 mg/kg, i.p, three times a week, for 9 weeks) produced kindled seizures in over 80% of the mice. Pretreatment with clozapine (1 or 5 mg) prevented the behavioral manifestations (motor seizures) as well as the development of kindling. The effect was compared with GABA (200 mg) and diazepam (1 mg), a known anticonvulsant drug.
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PMID:Protective effect of clozapine against pentylenetetrazol convulsions and kindling. 970 77

The GABA(A) receptor is a ligand gated chloride channel consisting of five membrane spanning proteins for which 13 different genes have been identified in the mammalian brain. The present review summarizes recent work from our laboratory on the characterization of the immunocytochemical distribution of these GABA(A) receptor subunits in the rat brain and changes in immunoreactivity and mRNA expression after kainic acid-induced status epilepticus. A heterogeneous distribution of immunoreactive GABA(A) receptor subunits was observed. The most abundant ones were: alpha1, alpha2, alpha4, alpha5, beta2, beta3, gamma2, and delta. Alpha1, beta2, and gamma2 were about equally distributed in all subfields of the hippocampus; alpha4- and delta-subunits were preferentially found in the dentate molecular layer and in CA1; alpha2 was localized to the dentate molecular layer and CA3; alpha5 was found in the dendritic areas of CA1 to CA3; and beta1 was preferentially seen in CA2. Alpha1, beta2, gamma2 and delta were highly concentrated in interneurons. Kainic acid-induced seizures caused acute and chronic changes in the expression of mRNAs and immunoreactive proteins. Acute changes included decreases in alpha2, alpha5, beta1, beta3, gamma2 and delta mRNA levels (by about 25-50%), accompanied by increases (by about 50%) in alpha1, alpha4, and beta2 messages in granule cells (after 6-12 h). Chronic changes, characterized by losses in mRNA and immunoreactive proteins in CA1 and CA3, are undoubtedly due to seizure-related cell damage. However, compensatory expression of alpha2 and beta3 subunits, especially in CA3b/c, was observed. Furthermore, increases in mRNAs and immunoreactive proteins were seen for alpha1, alpha2 alpha4, beta1, beta2, beta3 and gamma2 in granule cells and in the molecular layer of the dentate gyrus at 7-30 days after kainic acid injection. The changes in the expression of GABA(A) receptor subunits, observed in practically all hippocampal subfields, may reflect altered GABA-ergic transmission during development of the epileptic syndrome. Increased expression of GABA(A) receptor subunits in the dendritic field of granule cells and CA3 suggest that GABA-ergic inhibition may be augmented at these levels. However, the lasting preservation of alpha1-, beta2-, and gamma2-subunits in interneurons could provide a basis for augmented inhibition of GABA-ergic interneurons, leading to net disinhibition.
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PMID:Expression of GABA(A) receptor subunits in the hippocampus of the rat after kainic acid-induced seizures. 976 15


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