UMLS:C0038220 - FACTA Search

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

Hypoxia-ischemia, hypoglycemia, and status epilepticus damage specific regions in the developing brain. The factors which determine selective neuronal vulnerability have remained obscure but recent research suggests that the patterns may be related to dysfunction of specific sets of synapses. An important current hypothesis suggests that hyperactivity of excitatory synapses, which use neurotransmitters such as glutamate, may cause excessive transmitter release and lead to damage of adjacent neurons. Excessive stimulation of excitatory neurotransmitter receptors triggers a cascade of biochemical reactions and potentially lethal ionic shifts. Recent observations suggest that drugs acting at these receptors could be used to reduce brain injury caused by a variety of insults to the developing brain.
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PMID:New insights into mechanisms of neuronal damage in the developing brain. 287 53

There is convincing evidence that acidic amino acids, in particular L-glutamate, or substances containing them serve as the major excitatory neurotransmitters in the brain. At least three distinct receptors mediate the excitatory effects of this class of neurotransmitters. Pharmacological studies with agonists and antagonists of these receptors suggest that they may mediate the neurodegenerative consequences of Huntington's disease, status epilepticus, and hypoxemia, and that glutamate receptor antagonists have clinical potential as anticonvulsants, analgesics, and neuroprotective agents.
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PMID:Glutamate and related acidic excitatory neurotransmitters: from basic science to clinical application. 289 May 49

1. DL-C-Allyglycine, 4-deoxypyridoxine hydrochloride and 3-mercaptopropionic acid have been studied with reference to their convulsant effects in mice and in baboons (Papio papio) with photosensitive epilepsy, and their action on the cerebral enzyme synthesizing gamma-aminobutyric acid (L-glutamate-1-carboxy-lyase).2. In mice, the ED(50) values for seizures following intraperitoneal injection were allylglycine 1.0 mmol/kg body weight, 4-deoxypyridoxine 1.1 mmol/kg and 3-mercaptopropionic acid 0.27 mmol/kg. Latency to seizure onset was longest after allylglycine (44-240 min), intermediate after 4-deoxypyridoxine (9-114 min) and shortest after 3-mercaptopropionic acid (2.5-8 min).3. In Papio papio intravenous administration of subconvulsant doses of allylglycine (0.87-3.1 mmol/kg), or of 4-deoxypyridoxine (0.21-0.53 mmol/kg) enhanced the occurrence and persistence of myoclonic responses to intermittent photic stimulation, and augmented the associated electroencephalographic abnormalities, without modifying their character or distribution. Higher doses produced brief seizures recurring at regular intervals, between 2-14 h after allylglycine (4.0-4.3 mmol/kg) or 1-4 h after 4-deoxypyridoxine (0.53-0.87 mmol/kg). Electroencephalographically these seizures originated unilaterally in the occipital or posterior parietal cortex.4. In Papio papio photically-induced epileptic responses were enhanced 5-10 min after the intravenous injection of 3-mercaptopropionic acid (0.09-0.28 mmol/kg). A sequence of brief generalized seizures followed by complete recovery occurred 4-17 min after the injection of 3-mercaptopropionic acid (0.28-0.38 mmol/kg). Fatal status epilepticus followed the injection of 3-mercaptopropionic acid (0.57-0.75 mmol/kg). E.E.G. records showed generalized cortical involvement at the onset of the seizures.5. L-Glutamate 1-carboxy-lyase (GAD) activity was determined in whole brain homogenates from mice killed at various intervals after receiving i.p. a convulsant dose of one of the compounds. Inhibition of GAD activity was evident 30-60 min before seizure onset following allylglycine or 4-deoxypyridoxine administration, and was maximal (40-60%) just before or during seizure activity. Addition of pyridoxal phosphate to the brain homogenate relieved inhibition produced by 4-deoxypyridoxine but not that produced by allylglycine. Inhibition of GAD activity in brain homogenates from animals killed 2 or 4 min after injection of a convulsant dose of 3-mercaptopropionic acid varied from 0-49% depending on the dose of 3-mercaptopropionic acid and the concentration of substrate in the assay system.6. Kinetic analysis of the inhibition of GAD activity following direct addition of the compounds to mouse brain homogenates indicated that 3-mercaptopropionic acid (0.01-0.5 mM) was competitive with respect to the substrate. A comparable percentage inhibition of GAD activity was obtained only with much higher concentrations of 4-deoxypyridoxne, i.e. 10-50 mM. Allylglycine in vitro was a very weak inhibitor of GAD activity.7. Three biochemically different mechanisms underlie the inhibition of cerebral GAD activity that precedes seizures induced by ailylglycine, 4-deoxypyridoxine and 3-mercaptopropionic acid. The data are consistent with a critical reduction in the rate of synthesis of gamma-aminobutyric acid being responsible for the onset of seizures.
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PMID:Seizures induced by allylglycine, 3-mercaptopropionic acid and 4-deoxypyridoxine in mice and photosensitive baboons, and different modes of inhibition of cerebral glutamic acid decarboxylase. 420 45

Electrographic patterns induced by neocortical and hippocampal microinjections of kainic acid (KA) have been studied in curarized 4-30-day-old rats. In younger (4-6-day-old) animals, both hippocampal and neocortical KA application induced, with a long delay, the appearance of sequences of slow spikes, simultaneously occurring in the cortex and hippocampus. The same pattern was observed in about 60% of animals 7-9 days old. In the remaining 40% of the rats of this age, epileptic abnormalities, initially localized in the neocortical or hippocampal injection site were obtained. The latter pattern always appeared in 10-14-day-old rats. In some of these status epilepticus was also reached. In older (15-30 days) animals, the hippocampal injection caused the appearance of hippocampal seizures, always evolving into status epilepticus. In neocortically injected animals, cortical bursts of polyspikes appeared, with or without hippocampal involvement. After 40-60 min, typical hippocampal seizures occurred, later leading to status epilepticus. The simultaneous hippocampal and neocortical response observed in younger rats is attributed to a massive activation of the immature brain structures. The focal response seems to be correlated with a maturational process of glutamate and/or kainate receptors at both hippocampal and neocortical levels. This process is completed during the third week, when a typical selective activation of the limbic structures is obtained.
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PMID:Intracortical and intrahippocampal injections of kainic acid in developing rats: an electrographic study. 619 66

The heterocyclic compound kainic acid (KA) is a potent excitant when applied to mammalian neurones. Lesions caused by injections of KA into the rat striatum and hippocampus cause similar patterns of damage to those seen in Huntington's chorea and status epilepticus, respectively. Although it was originally thought to be a glutamate agonist, it is now clear that KA does not act on the majority of the receptors for glutamate, and in fact seems to act on a class of receptors which are distinct from those which mediate responses to other excitatory amino acids. The potent and selective neurotoxic effects of this compound may be mediated by these same receptors. At present, the relative distribution of junctional and extrajunctional (non-synaptic) receptors is unknown and resolution of this issue would provide important insights into the action of KA on the central nervous system (CNS). We show here that KA binding sites are greatly enriched in isolated synaptic junctions from rat brain and, using an in vitro autoradiographic technique, we have found that these binding sites are concentrated specifically in terminal fields where KA acts as a potent neurotoxin.
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PMID:Synaptic localization of kainic acid binding sites. 625 47

Quisqualic acid (QA) is a potent neuroexcitant and a heterocyclic analogue of glutamate as is kainic acid. Twenty micrograms of QA in unilateral lateral amygdaloid nucleus of cats produced a transient limbic status epilepticus lasting 20-30 hours. Over 14 days after recovery from the limbic status, the animals received daily electrical stimulation to the ipsilateral hippocampus at the intensity of afterdischarge threshold which was determined before the injection of QA. These stimulations resulted in secondarily generalized convulsive seizures in all animals within 4 to 12 days. Spontaneous secondarily generalized seizures were confirmed in two cats after completion of the hippocampal kindling. This rapid completion of the kindling process is interesting phenomenon in contrast to the report that the hippocampal kindling took nearly 60 days. This rapid completion of the kindling effect is considered to be due to the transfer effect (Goddard, 1975) established in the ipsilateral hippocampus by severe bombardments from the amygdala stimulated by the injection of QA as the primary focus. In addition, the pathological changes in the amygdala and hippocampus on the injected side might be related to the rapid kindling process of the ipsilateral hippocampus as the irritable foci.
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PMID:[Rapid hippocampal kindling following intraamygdaloid injection of quisqualic acid in cats]. 635 21

1. In this report we compare changes in inhibitory neurotransmission within the CA1 region and the dentate gyrus (DG) in a model of chronic temporal lobe epilepsy (TLE). Extracellular and intracellular recordings were obtained in combined hippocampal-parahippocampal slices > or = 1 mo after a period of self-sustaining limbic status epilepticus (SSLSE) induced by continuous hippocampal stimulation. 2. Polysynaptic inhibitory postsynaptic potentials (IPSPs) were induced by positioning electrodes to activate specific afferent pathways and evoking responses in the absence of glutamate receptor antagonists [D(-)-2-amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)]. Polysynaptic IPSPs were evoked in CA1 pyramidal cells from electrodes positioned in stratum radiatum and in stratum lacunosum/moleculare. Polysynaptic IPSPs were evoked in DG granule cells from electrodes positioned over the perforant path located in the subiculum. Monosynaptic IPSPs were induced by positioning electrodes within 200 microns of the intracellular recording electrode (near site stimulation) and stimulating in the presence of APV and CNQX to block ionotropic glutamate receptors. Monosynaptic IPSPs were evoked in CA1 pyramidal cells with electrodes positioned in the stratum lacunosum/moleculare and stratum pyramidale. Monosynaptic IPSPs were evoked in DG granule cells with electrodes positioned in the stratum moleculare. 3. Population spike (PS) amplitudes were employed to assure that a full range of stimulus strengths, from subthreshold for action potentials to an intensity giving maximal-amplitude PSs, was used to elicit polysynaptic IPSPs in CA1 pyramidal cells in both post-SSLSE and control slices. In control tissue, polysynaptic IPSPs were biphasic, composed of early and late events. In post-SSLSE tissue, polysynaptic IPSPs were markedly diminished. The diminution of polysynaptic IPSPs was detected at all levels of stimulus intensity. Both early IPSPs [mediated by gamma-aminobutyric acid-A (GABAA) receptors] and late IPSPs (mediated by GABAB receptors) were diminished. Polysynaptic IPSPs were diminished with both stratum radiatum and with stratum lacunosum/moleculare stimulation. 4. Reversal potentials for either polysynaptic early or polysynaptic late IPSPs evoked in CA1 pyramidal cells by stratum radiatum stimulation were not different in slices from post-SSLSE animals as compared with control animals. Likewise, reversal potentials for either polysynaptic early or polysynaptic late IPSPs evoked by stratum lacunosum/moleculare stimulation did not differ in the two groups. These findings excluded changes in driving force as an explanation for the diminished amplitude of IPSPs in CA1 pyramidal cells in the post-SSLSE model.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Changes in inhibitory neurotransmission in the CA1 region and dentate gyrus in a chronic model of temporal lobe epilepsy. 747 86

In the present investigation we address the question of whether one of the responses to increased neuronal activity is a modification of the expression of the different subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-selective glutamate receptors (GluR-1, GluR-2, GluR-3). Thus, we used two different models of generalized status epilepticus, as widespread elevated neuronal activity, to study in vivo responses of the AMPA receptor mRNA expression in rat forebrain. By Northern blot analysis and in situ hybridization, we show that one of the delayed responses to LiCl/pilocarpine-induced status epilepticus is a dramatic change in the mRNA level of some subunits of AMPA-selective glutamate receptors. These effects, which appear between 6 and 12 h after the drug treatment, are subunit and brain region specific. The most striking example of differential expression of the three examined GluR mRNAs can be observed in the dentate gyrus of the hippocampus. In this specific brain subregion an increase of GluR-3 mRNA level is induced 12 h after LiCl/pilocarpine treatment, while a clear decrease in GluR-1 mRNA level and no significant change in GluR-2 mRNA level can be observed in the same area under these experimental conditions. Both the GluR-1 decrease and the GluR-3 increase are transient effects and a return to basal level can be observed after 48-72 h. In the CA1 layer of the hippocampus, a parallel decrease of both GluR-1 and GluR-3 expression is found 12-24 h after drug treatment, followed by a recovery of the expression to control values at 48 h. In kainate-induced epilepsy we could reproduce the late increase (12-24 h) in GluR-3 mRNA in the dentate gyrus; however, under this experimental condition, no clear decrease of GluR-1 expression can be observed in this area. A general decrease in mRNA level for the AMPA receptor subunits (GluR-1-3) in the hippocampal layers, in particular in CA3 and CA4 subfields, was also observed. In conclusion the results reported in the present paper reveal a specific regulation of GluR gene expression in the granule cells of the hippocampal dentate gyrus and stimulate further investigation on the functional role of the GluR-3 subunit in the receptor-channel complex.
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PMID:Changes in gene expression of AMPA-selective glutamate receptor subunits induced by status epilepticus in rat brain. 752 10

It has been suggested that nitric oxide (NO) interferes with both glutamatergic neurotransmission and the regulation of cerebral blood flow in epileptic seizures. This study examines the effect of an inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg), on the extracellular concentration of glutamate during seizures induced by kainic acid (KA; 10 mg/kg), both drugs being administered systemically. L-NAME was injected 40 min before KA. The extracellular glutamate concentration was measured in the hippocampus of awake, spontaneously breathing rats using microdialysis combined with HPLC. The arterial blood gases and glycemia were periodically checked. The arterial blood pressure, the electrocorticogram and the body temperature were continuously monitored. In basal conditions, the systemic injection of L-NAME increased arterial blood pressure but did not significantly change the hippocampal glutamate level. In seizure conditions, the hippocampal glutamate concentration was either slightly increased or not significantly changed in saline-treated rats (n = 6) but it was decreased in L-NAME-treated rats (n = 6). At all times after KA injection, the hippocampal glutamate concentration was significantly lower in L-NAME-treated rats than in saline-treated rats. Unlike saline-treated rats, L-NAME-treated rats died during status epilepticus. This study shows that acute systemic injection of L-NAME reduces the extracellular concentration of glutamate in the rat hippocampus during seizures induced by KA.
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PMID:Effect of inhibiting NO synthesis on hippocampal extracellular glutamate concentration in seizures induced by kainic acid. 760 44

The etiology of cerebral abnormalities after focal status epilepticus (SE) is unknown. Possible causes include hypoxia and the excessive release of excitatory amino acids. Magnetic resonance imaging (MRI) of a 21-year-old patient with "cryptogenic" continuous motor seizures showed swelling and signal hyperintensity of the contralateral parietotemporal cortex, the thalamus, and the ipsilateral cerebellum on T2-weighted images. These regions are connected by glutamatergic pathways. Proton magnetic resonance spectroscopy (MRS) of the cortical lesion yielded a signal peak at the resonance frequency of 2.29 ppm, suggesting a focal increase of glutamate or its degradation product glutamine. At 3-month follow-up, structural alterations had disappeared, but the N-acetyl-aspartate/choline ratio was still reduced in the previously abnormal area. These findings are the first to demonstrate the contribution of MRS to pathophysiologic studies of focal SE in humans and, in combination with the pattern of imaging abnormalities, support a major role of glutamate for seizure-related brain damage.
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PMID:Magnetic resonance imaging and spectroscopy findings after focal status epilepticus. 764 36

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