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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Long-term GABA(A) receptor alterations occur in hippocampal dentate granule neurons of rats that develop epilepsy after status epilepticus in adulthood. Hippocampal GABA(A) receptor expression undergoes marked reorganization during the postnatal period, however, and the effects of neonatal status epilepticus on subsequent GABA(A) receptor development are unknown. In the current study, we utilize single cell electrophysiology and antisense mRNA amplification to determine the effect of status-epilepticus induced by lithium-pilocarpine in postnatal day 10 rat pups on GABA(A) receptor subunit expression and function in hippocampal dentate granule neurons. We find that rats subjected to lithium-pilocarpine-induced status epilepticus at postnatal day 10 show long-term GABA(A) receptor changes including a two-fold increase in alpha1 subunit expression (compared with lithium-injected controls) and enhanced type I benzodiazepine augmentation that are opposite of those seen after status epilepticus in adulthood and may serve to enhance dentate gyrus inhibition. Further, unlike adult rats, postnatal day 10 rats subjected to status epilepticus do not become epileptic. These findings suggest age-dependent differences in the effects of status epilepticus on hippocampal GABA(A) receptors that could contribute to the selective resistance of the immature brain to epileptogenesis.
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PMID:Effects of status epilepticus on hippocampal GABAA receptors are age-dependent. 1506 73

Formation of local excitatory circuits may contribute to epileptogenesis. We tested the hypothesis that epileptogenesis is associated with increased recurrent excitation in the hippocampal CA1 area of rats with kainate-induced epilepsy. Whole cell recordings were obtained during focal flash photolysis of caged glutamate, which served as a focal excitant to activate local pyramidal cells and to study possible connections between neurons. Kainate-treated rats with spontaneous seizures were studied months after status epilepticus and were compared with saline-injected control rats. Experiments were done in isolated CA1 minislices and in bicuculline to block GABA(A) receptors. Spontaneous excitatory postsynaptic currents (sEPSCs) were present in 42% of the CA1 pyramidal cells from controls and 62% from kainate-treated rats. The frequency of sEPSCs in the kainate group was significantly higher than that in the control group, but mean amplitude was not different. Flash photolysis of caged glutamate on the somatodendritic area of CA1 pyramidal neurons caused a burst of action potentials. Local excitatory connections between CA1 pyramidal cells were found in 4 of 48 neurons (8%) in slices from control animals, but in significantly more neurons (12 of 37; 32%) from rats with kainate-induced epilepsy exhibited interconnections (P < 0.001). Photoactivation of glutamate on recorded CA1 pyramidal cells in the kainate group sometimes caused afterdischarges, but not in controls. The kainate-treated rats with pyramidal cells that responded to photostimulaltion with repetitive EPSCs appeared to have experienced more severe seizures. These data provide new electrophysiological evidence for the formation of recurrent excitatory circuits in the CA1 area of rats with kainate-induced epilepsy.
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PMID:Increased excitatory synaptic activity and local connectivity of hippocampal CA1 pyramidal cells in rats with kainate-induced epilepsy. 1508 40

This review focuses on the remodeling of brain circuitry associated with epilepsy, particularly in excitatory glutamate and inhibitory GABA systems, including alterations in synaptic efficacy, growth of new connections, and loss of existing connections. From recent studies on the kindling and status epilepticus models, which have been used most extensively to investigate temporal lobe epilepsy, it is now clear that the brain reorganizes itself in response to excess neural activation, such as seizure activity. The contributing factors to this reorganization include activation of glutamate receptors, second messengers, immediate early genes, transcription factors, neurotrophic factors, axon guidance molecules, protein synthesis, neurogenesis, and synaptogenesis. Some of the resulting changes may, in turn, contribute to the permanent alterations in seizure susceptibility. There is increasing evidence that neurogenesis and synaptogenesis can appear not only in the mossy fiber pathway in the hippocampus but also in other limbic structures. Neuronal loss, induced by prolonged seizure activity, may also contribute to circuit restructuring, particularly in the status epilepticus model. However, it is unlikely that any one structure, plastic system, neurotrophin, or downstream effector pathway is uniquely critical for epileptogenesis. The sensitivity of neural systems to the modulation of inhibition makes a disinhibition hypothesis compelling for both the triggering stage of the epileptic response and the long-term changes that promote the epileptic state. Loss of selective types of interneurons, alteration of GABA receptor configuration, and/or decrease in dendritic inhibition could contribute to the development of spontaneous seizures.
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PMID:Kindling and status epilepticus models of epilepsy: rewiring the brain. 1519 78

Mice with targeted deletion of the GABA catabolic enzyme succinic semialdehyde dehydrogenase (SSADH) manifest lethal tonic-clonic seizures, amenable to pharmacologic rescue, at 3-4 weeks of life. In the current report, we characterized amino acid profiles in SSADH(-/-) brain utilizing whole brain and regional extracts (frontal and parietal cortex, hippocampus, and cerebellum) to develop hypotheses concerning epileptogenesis. Of 35 amino acids quantified, we found significant dysregulation in SSADH(-/-) mice for 11 (GABA, glutamate, glutamine, alanine, aspartate, serine, taurine, cystathionine, methionine, homocarnosine, and arginine) as compared to age-matched littermates both before, and following, the period of generalized convulsive seizures and status epilepticus. Our results reveal imbalanced amino acid levels potentially involved in the transition from absence seizures to generalized convulsive seizures resulting in SSADH(-/-) mice. We conclude that the SSADH(-/-) mouse represents a unique epileptic model with the potential to reveal novel aspects of excitatory/inhibitory interactions in the genesis of seizures.
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PMID:Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency. 1526 67

Transplantation of neural stem cells (NSCs) can replace lost neurons and improve the functional deficits. Cell transplantation strategies have been tried in the epileptic disorder, but the effect of exogenous NSCs is unknown. In this study, we attempted to test the anti-epileptogenic effect of NSCs in adult rats with status epilepticus. Experimental status epilepticus was induced by lithium-pilocarpine injection, and beta galactosidase-encoded human NSCs were transplanted intravenously on the next day of status epilepticus. Spontaneous recurrent seizures were monitored with Racine's seizure severity scale. Immunohistochemistry with anti-beta gal, Tuj-1, NeuN, GFAP, CNPase, GluR2, parvalbumin, and GABA were performed and extracellular field excitatory postsynaptic potentials (fEPSP) were recorded. Human NSCs suppressed spontaneous recurrent seizure formation and transplanted NSCs were differentiated into GABA-immunoreactive interneurons in the damaged hippocampus. Amplitude of fEPSP in the hippocampal CA1 was reduced, which was reversed by picrotoxin. These findings suggest that NSCs could be differentiated into inhibitory interneurons and decrease neuronal excitability, which could prevent spontaneous recurrent seizure formation in adult rats with pilocarpine-induced status epilepticus.
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PMID:Human neural stem cell transplantation reduces spontaneous recurrent seizures following pilocarpine-induced status epilepticus in adult rats. 1537 47

delta Subunit-containing GABA(A) receptors are located predominantly at nonsynaptic sites in the dentate gyrus where they may play important roles in controlling neuronal excitability through tonic inhibition and responses to GABA spillover. Immunohistochemical methods were used to determine whether delta subunit expression was altered after pilocarpine-induced status epilepticus in C57BL/6 mice in ways that could increase excitability of the dentate gyrus. In pilocarpine-treated animals, the normal diffuse labeling of the delta subunit in the dentate molecular layer was decreased by 4 d after status epilepticus (latent period) and remained low throughout the period of chronic seizures. In contrast, diffuse labeling of alpha4 and gamma2 subunits, potentially interrelated GABA(A) receptor subunits, was increased during the chronic period. Interestingly, delta subunit labeling of many interneurons progressively increased after pilocarpine treatment. Consistent with the observed changes in delta subunit labeling, physiological studies revealed increased excitability in the dentate gyrus of slices obtained from the pilocarpine-treated mice and demonstrated that physiological concentrations of the neurosteroid tetrahydrodeoxycorticosterone were less effective in reducing excitability in the pilocarpine-treated animals than in controls. The findings support the idea that alterations in nonsynaptic delta subunit-containing GABA(A) receptors in both principal cells and interneurons could contribute to increased seizure susceptibility in the hippocampal formation in a temporal lobe epilepsy model.
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PMID:Altered expression of the delta subunit of the GABAA receptor in a mouse model of temporal lobe epilepsy. 1614 12

GABAergic inhibition of the substantia nigra pars reticulata (SNR) has been shown to suppress seizures in most models of epilepsy, including the amygdala-kindling model of temporal lobe epilepsy (TLE). A dysfunction of this seizure gating mechanism of the SNR may lead to facilitation of seizure propagation in such models. In post-status epilepticus models of TLE, GABAergic neurons in the SNR are damaged, but it is not known whether such damage also occurs in kindling. By using stereological techniques for cell counting in amygdala-kindled rats, we determined the density of SNR neurons that were labeled for GABA by immunohistochemistry or for the two isoforms of the GABA-synthesizing enzyme glutamate decarboxylase (GAD), GAD65 and GAD67, by in situ hybridization (ISH). In addition, GABA neurons in the basolateral amygdala (BLA) were counted. While there was a significant reduction of GAD65 mRNA expressing neurons in the BLA of kindled rats, no alteration in the density of neurons was observed in the anterior or posterior SNR when cells were counted 6 weeks after the last kindled seizure. Our previous finding of reduced GAD and GABA levels in synaptosomes isolated from the SN of kindled rats together with the present observation of unchanged density of SNR neurons in such rats suggest that kindling affects the GABAergic projections from the striatum or globus pallidus to the SNR rather than directly affecting GABA neurons in the SNR.
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PMID:Amygdala-kindling does not induce a persistent loss of GABA neurons in the substantia nigra pars reticulata of rats. 1546 61

While it is clear that acute hippocampal injury or status epilepticus increases the production of new neurons in the adult dentate gyrus (DG), the effects of chronic epilepsy on dentate neurogenesis are unknown. We hypothesize that epileptogenic changes and spontaneous recurrent motor seizures (SRMS) that ensue after hippocampal injury or status epilepticus considerably decrease dentate neurogenesis. We addressed this issue by quantifying the number of cells that are positive for doublecortin (DCX, a marker of new neurons) in the DG of adult F344 rats at 16 days and 5 months after an intracerebroventricular kainic acid (ICV KA) administration or after graded intraperitoneal KA (IP KA) injections, models of temporal lobe epilepsy (TLE). At early post-KA administration, the injured hippocampus exhibited increased dentate neurogenesis in both models. Conversely, at 5 months post-KA administration, the chronically epileptic hippocampus demonstrated severely declined neurogenesis, which was associated with considerable SRMS in both KA models. Additionally, stem/progenitor cell proliferation factors, FGF-2 and IGF-1, were decreased in the chronically epileptic hippocampus. Interestingly, the overall decrease in neurogenesis and the extent of SRMS were greater in rats receiving IP KA than rats receiving ICV KA, suggesting that the extent of neurogenesis during chronic TLE exhibits an inverse relationship with SRMS. These results provide novel evidence that chronic TLE is associated with extremely declined dentate neurogenesis. As fraction of newly born neurons become GABA-ergic interneurons, declined neurogenesis may contribute to the increased seizure-susceptibility of the DG in chronic TLE. Likewise, the hippocampal-dependent learning and memory deficits observed in chronic TLE could be linked at least partially to the declined neurogenesis.
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PMID:Chronic temporal lobe epilepsy is associated with severely declined dentate neurogenesis in the adult hippocampus. 1557 83

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

Within the area tempestas (AT) in the anterior piriform cortex, unilateral microinfusions of GABA receptor antagonists and glutamate receptor agonists trigger brief episodic limbic seizures. In the present study, we document a synergistic effect of coinfusing bicuculline (GABAA receptor antagonist) with either carbachol (muscarinic receptor agonist) or cyclothiazide (inhibitor of AMPA receptor desensitization) but not with glutamate receptor agonists (AMPA, NMDA or kainate) in the rat AT. In particular, coadministration of bicuculline (118 pmol) with either carbachol (328 pmol) or cyclothiazide (1.2 nmol) triggered continuous self-sustaining seizures (status epilepticus; SE). Cyclothiazide alone did not evoke seizures. Although blockade of NMDA receptors with AP-7 (100 or 500 pmol) prevented episodic seizures evoked by carbachol or bicuculline alone, it was without effect on the continuous seizures evoked by combined treatments. NMDA-insensitive self-sustaining seizures were also evoked by the combination of AMPA and cyclothiazide. Regardless of the mechanism by which SE was evoked, it was prevented only by an AMPA receptor antagonist, NBQX, thus reinforcing the crucial role of AMPA receptors in the transition to SE. Further evidence for AMPA receptor regulation of seizure severity came from the overexpression of the GluR1 AMPA receptor subunit in AT. This resulted in substantially increased severity of bicuculline-evoked seizures that was reversed by focal application of NBQX. Thus, desensitization of AMPA receptors appears to limit the duration and severity of seizure activity, and a failure of this mechanism, or an overabundance of slowly desensitizing AMPA receptors, predisposes to severe and prolonged seizures.
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PMID:AMPA receptor desensitization as a determinant of vulnerability to focally evoked status epilepticus. 1567 44


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