Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The level of the mRNAs encoding the AMPA-selective glutamate receptors-A and -B, alternatively splice variants, Flip and Flop, was studied by in situ hybridization in the brains of rats kindled by Schaffer collateral/commissural-fiber stimulation. In comparison to control animals, the expression level of the Flip variant of both GluR-A and GluR-B mRNAs was bilaterally enhanced in the dentate granule neurons of kindled animals 24 h after last-generalized seizure, whereas no obvious alterations were observed in the GluR-A Flop and GluR-B Flop mRNA variants. In kindled animals, studied 1 month after the last seizure, GluR-A Flip and GluR-B Flip mRNA had returned to control levels. We suggest that these changes may result in an enhanced glutamate receptor sensitivity in the fascia dentata during kindling.
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PMID:Hippocampal kindling increases the expression of glutamate receptor-A Flip and -B Flip mRNA in dentate granule cells. 130 May 3

Following lesions of the fimbria-fornix, there is a time-dependent increase in interictal spikes and seizure susceptibility. This may result from sprouting of local excitatory and inhibitory circuits in response to the loss of subcortical and commissural innervation of the hippocampal formation. We used receptor autoradiography to examine the density of N-methyl-D-aspartate (NMDA)-sensitive L-[3H]glutamate and [3H]-kainate (KA) binding sites in the hippocampal formation at 5 days, 3 months, and 1 year following bilateral aspiration lesions of the fimbria-fornix. At 5 days post-lesion, the CA3 and CA1 strata radiatum and oriens displayed a decrease (20-42%, P less than 0.01) in NMDA-sensitive L-[3H]glutamate binding. The initial decrease was followed by a moderate recovery at later time points but was still evident at 1 year postlesion. This may reflect a lesion-induced turnover of synaptic complexes, down-regulation of postsynaptic receptors, or loss of presynaptic receptors. Five days following fimbria-fornix lesion there was also a decrease (13-15%, P less than 0.05) in [3H]KA binding in CA3 strata radiatum and pyramidale. However, at 3 months postlesion KA receptor density was elevated by 29-33% (P less than 0.01) in the outer molecular layer of the dentate gyrus with no significant change in binding to the inner molecular layer. By 1 year postlesion, the density of [3H]KA binding sites was not significantly different from that observed in control animals of the same age. The increase in KA receptor density in the outer molecular layer 3 months after fimbria-fornix lesion may reflect sprouting of the perforant path input or mossy fibers to this region and contribute to the increase in interictal spikes and seizures susceptibility.
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PMID:Alterations in [3H]kainate and N-methyl-D-aspartate-sensitive L-[3H]-glutamate binding in the rat hippocampal formation following fimbria-fornix lesions. 131 Apr 74

A hypothesis is presented to explain the influence of alcohol on glutamate generated excitotoxicity. Chronic alcohol exposure is reported to increase glutamate-N-methyl-D-aspartate (NMDA) receptors and calcium ion channel activity, resulting in the neurotoxicity and seizure activity associated with alcohol withdrawal in certain persons. Recent information indicates that nitric oxide is responsible for the neurotoxicity associated with excessive glutamate stimulation of NMDA receptors. Thus, it is hypothesized that nitric oxide is involved in producing the neurotoxicity and cell disturbances associated with chronic alcohol exposure.
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PMID:Alcohol, nitric oxide, and neurotoxicity: is there a connection?--a review. 132 Aug 8

A study was performed to examine the specific binding of excitatory amino acid (EAA) receptor subtypes in 5 brain regions of rats kindled from the amygdala or hippocampus, using extensively washed and Triton X-100-treated membranes. Seven days after the last amygdala kindled seizure, [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10- imine maleate ([3H]MK-801) binding, which labels N-methyl-D-aspartate (NMDA)-sensitive receptor-linked cation channels, decreased significantly only in the amygdala of kindled rats compared to that of controls under equilibrium assay conditions. There was no significant change in [3H]MK-801 binding in the amygdala or hippocampus 7 days after the last hippocampal kindled seizure, or 28 days after the last amygdala kindled seizure. Nor was there a significant change in NMDA-sensitive [3H]glutamate, strychnine-insensitive [3H]glycine, [3H]spermidine, [3H]kainate or [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA) binding in any brain region 7 days after the last amygdala kindled seizure, or in the hippocampus 28 days after the last amygdala kindled seizure. These results indicate that [3H]MK-801 binding sites labeling NMDA-sensitive receptor-linked cation channels in the amygdala undergo downregulation only transiently, but that none of the subcomponents of the NMDA receptor macromolecular complex exhibit enduring changes at steady state following the completion of amygdala kindling.
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PMID:Ionotropic excitatory amino acid receptors in discrete brain regions of kindled rats. 132 75

A brief application of high K+ or excitatory amino acids (i.e. kainic acid) generated repetitive synchronized burst that persisted for the duration of the application, in the CA3 field. Once excitability has been enhanced, further stimulation of various inputs evoked burst instead the typical excitatory postsynaptic potential--inhibitory postsynaptic potential sequence evoked in control conditions. These long-lasting changes in synaptic efficacy involved the activation of glutamate receptors of N-methyl-D-aspartate (NMDA) subtype. A brief period of hyperactivity (i.e. kindling of limbic pathways or administration of kainic acid) also resulted in a more delayed synaptic remodeling, notably of hippocampal mossy fibers (i.e. the axons of granule cells that mostly contact the apical dendrites of CA3 pyramidal neurons). Thus mossy fibers sprouted and made multiple ectopic asymmetrical synapses with spines of both granule cells dendrites and basilar dendrites of CA3 pyramidal cells. Finally, sprouting of mossy fibers was associated with a significant rise in the density of kainic acid binding sites (fmol/mg tissue) in the aberrantly innervated zones: the inner third of molecular layer and the stratum oriens of CA3. Saturation studies revealed that this rise did not significantly affect the affinity (Kd values) but the Bmax. In conclusion, brief seizure episodes produced in the hippocampus remarkably long-lasting changes in synaptic efficacy; synaptic density and the mean density of excitatory amino acid receptors of non-NMDA subtype. The role that such plastic changes may play in the permanence of the epilepsy is finally discussed.
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PMID:Long-term potentiation and sprouting of mossy fibers produced by brief episodes of hyperactivity. 133 65

Two potent glutamate antagonists, NBQX and GYKI 52466, that act selectively on non-NMDA receptors, have been tested for anticonvulsant activity in 3 models of reflex epilepsy (sound-induced seizures in DBA/2 mice and in genetically epilepsy-prone rats and photically-induced myoclonus in Papio papio) and in amygdala kindled rats. Both compounds potently but transiently suppress reflexly-induced epileptic responses. GYKI 52466 also reduces behavioral seizures and afterdischarge duration in amygdala kindled rats, but with a lower potency than it suppresses reflex epilepsy. These data are similar to earlier results with antagonists acting selectively on NMDA receptors; they do not support a specific involvement of enhanced AMPA receptor sensitivity as a major factor in the expression of kindled seizures.
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PMID:The effects of AMPA receptor antagonists on kindled seizures and on reflex epilepsy in rodents and primates. 133 44

U-54494A, a 1,2-diamine anticonvulsant, and U-50488H, a structurally related agonist for opiate kappa receptors, were tested for effects on spontaneous and glutamate-evoked firing rates in cerebral cortex of urethane-anesthetized male Sprague-Dawley rats. Iontophoretic application of 1,2-diamines, glutamate diethyl ether (GDEE), or procaine depressed spontaneous and amino acid-induced firing of cortical neurones. With continued ejection of 1,2-diamines or procaine, firing was silenced completely, but GDEE could maintain a partial suppression. A rapid rebound of excitation followed cessation of procaine ejections, but not of other agents. Procaine, but not U-54494A, blocked axonal conduction of rabbit sciatic nerve. Intravenous U-54494A and U-50488H significantly depressed spontaneous firing rates of cortical neurones, but only the U-50488H effects were antagonized by naloxone. It is concluded that U-54494A inhibits neuronal excitability by a mechanism independent of the analgesic kappa receptor. Biochemical and physiological studies have demonstrated that U-54494A and the kappa opioid agonist U-50488H (a structurally related diamine) (1) have anticonvulsant activity (2, 3). U-54494A lacks kappa analgesic and sedative properties, and it has been suggested that the mechanism of action of this compound may be mediated by a subtype of kappa opioid receptor (3). The effects of kappa analgesics on neuronal firing in nociceptive pathways have been described (4, 5). However, no previous electrophysiological studies on U-54494A have been done. Since U-54494A antagonizes amino acid-induced seizures (3), the interactions of this compound with glutamate are of interest. In the present study, the antagonist efficacies of U-54494A and U-50488H for inhibiting spontaneous and 1-glutamate stimulated neurons of the rat prefrontal cerebral cortex were assessed after i.v. and microiontophoretic administration of the compounds. Effects observed with these routes of administration allow the observation of neuronal changes occurring immediately after administration and take advantage of the high temporal resolution provided by the electrophysiological recording techniques of single cells. A preliminary account of portions of this work have been previously disclosed (6).
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PMID:Effect of the anticonvulsant U-54494A on cortical neuron excitability: comparison to the kappa agonist U-50488H. 134 50

The postsynaptic actions of glutamate, gamma-aminobutyric acid (GABA), acetylcholine, norepinephrine, serotonin, and histamine in the cerebral cortex and thalamus and their relevance to the control of thalamocortical activity are reviewed. Excitatory and inhibitory amino acids (such as glutamate and GABA) are proposed to form the neurotransmitters by which the executative neural networks of the neocortex and thalamus process synaptic information. In contrast, the more slowly acting neurotransmitters, acetylcholine, norepinephrine, serotonin, and histamine, are proposed to control the state of activity and excitability of thalamic and cortical neurons and thereby modulate the state of thalamocortical activity. Specific examples of the involvement of fast and slow transmitter actions in the genesis of epileptic seizures and the determination of sleep-wake cycles are given.
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PMID:Neurotransmitter actions in the thalamus and cerebral cortex. 135 May 91

1. We studied the effect of pentylenetetrazol (PTZ)-induced myoclonic jerks and generalized clonic-tonic convulsions (GC) on the levels of neurotransmitter amino acids in the cisternal CSF of rats. 2. The levels of aspartate, glutamate, glycine, and taurine were elevated in the CSF during myoclonic jerks and more distinctly immediately after GC. 3. During the recovery period of postictal depression seen in EEG (5 min after GC), the CSF levels of transmitter amino acids were lower than in the control group. 4. PTZ-induced irritative activity in the EEG disappeared in 24 hr but the levels of amino acids remained abnormal. 5. Amino acid changes in the CSF following PTZ-induced convulsions might indicate that the release of amino acids into the extracellular space is increased before and during the propagation of PTZ-induced seizure and decreased during postictal depression.
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PMID:Amino acid levels in cerebrospinal fluid of rats after administration of pentylenetetrazol. 135 Sep 65

Seizures elicited by posture change and intraperitoneal administration of convulsants were studied ontogenetically in the Mongolian gerbil (Meriones unguiculatus). In posture change, the first signs of seizure appeared after age 6 weeks with maximal frequency at 8-9 weeks. Adults developed complex, but stereotyped, seizures. Facial twitch was followed by the generalized convulsion, further progressing to trembling of the limbs and then kicking of the hindlimb (full seizure) after 55 days of age. Pentylenetetrazole induced a seizure similar to the full event in gerbils as young as 37 days of age. The seizure pattern elicited by strychnine or glutamate was different from that of pentylenetetrazole.
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PMID:Intrinsic and drug-induced seizures of adult and developing gerbils. 135 21


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