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)

To elucidate the intracellular mechanism of the bursting activity which is characteristic of seizure discharge, the behavior of the intracellular cyclic nucleotide and the intracellular calcium during pentylenetetrazole (PTZ)-induced bursting activity in snail neurons was investigated. Cyclic AMP was increased about 3-fold by the incubation of ganglia with PTZ. The effect of PTZ on phosphodiesterase activity measured using either cyclic AMP or cyclic GMP as substrate showed a slight increase in cyclic AMP phosphodiesterase activity. The release of calcium from the lysosome fraction was increased by the incubation of ganglia with dibutyryl cyclic AMP. Protein kinase activity was stimulated by the incubation of ganglia with PTZ. Adenylate cyclase activity was stimulated by the incubation of ganglia with PTZ. These findings suggest that PTZ-induced bursting activity in snail neurons is initiated by an intracellular increase of cyclic AMP, which promotes calcium release from lysosomes and induces protein kinase activation.
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PMID:Behavior of intracellular cyclic nucleotide and calcium in pentylenetetrazole-induced bursting activity in snail neurons. 630 20

The high seizure susceptibility in epileptic fowl is due to an autosomal recessive mutation. Cyclic AMP and cyclic GMP concentrations were determined in brains from two day old epileptic chicks (homozygotes) during an inter-ictal period as well as during and following a seizure evoked by stroboscopic stimulation. The data were compared to values obtained from non-epileptic carrier chicks (heterozygotes) sacrificed in an unstimulated state or subjected to the seizure evoking stimulus. During the inter-ictal state in epileptics no abnormalities were found in cyclic nucleotide concentrations indicating that the high seizure susceptibility is not related to abnormalities of these nucleotides. Although seizure activity in epileptics was associated with reduced cyclic AMP in the optic lobes this also occurred in carrier chicks subjected to the seizure evoking stimulus. The only significant changes in cyclic GMP levels, occurring as a result of seizures in epileptics, were an increase in cyclic GMP in the cerebral hemispheres during the seizure and a decrease in the optic lobes during the postictal period.
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PMID:Cyclic nucleotides and seizures in a hereditary model of epilepsy. 632 61

The objective of the present experiments was to study metabolic correlates to the localization of neuronal lesions during sustained seizures. To that end, status epilepticus was induced by i.v. administration of bicuculline in immobilized and artificially ventilated rats, since this model is known to cause neuronal cell damage in cerebral cortex and hippocampus but not in the cerebellum. After 20 or 120 min of continuous seizure activity, brain tissue was frozen in situ through the skull bone, and samples of cerebral cortex, hippocampus, and cerebellum were collected for analysis of glycolytic metabolites, phosphocreatine (PCr), ATP, ADP, AMP, and cyclic nucleotides. After 20 min of seizure activity, the two "vulnerable" structures (cerebral cortex and hippocampus) and the "resistant" one (cerebellum) showed similar changes in cerebral metabolic state, characterized by decreased tissue concentrations of PCr, ATP, and glycogen, and increased lactate concentrations and lactate/pyruvate ratios. In all structures, though, the adenylate energy charge remained close to control. At the end of a 2-h period of status epilepticus, a clear deterioration of the energy state was observed in the cerebral cortex and the hippocampus, but not in the cerebellum. The reduction in adenylate energy charge in the cortex and hippocampus was associated with a seemingly paradoxical decrease in tissue lactate levels and with failure of glycogen resynthesis (cerebral cortex). Experiments with infusion of glucose during the second hour of a 2-h period of status epilepticus verified that the deterioration of tissue energy state was partly due to reduced substrate supply; however, even in animals with adequate tissue glucose concentrations, the energy charge of the two structures was significantly lowered. The cyclic nucleotides (cAMP and cGMP) behaved differently. Thus, whereas cAMP concentrations were either close to control (hippocampus and cerebellum) or moderately increased (cerebral cortex), the cGMP concentrations remained markedly elevated throughout the seizure period, the largest change being observed in the cerebellum. It is concluded that although the localization of neuronal damage and perturbation of cerebral energy state seem to correlate, the results cannot be taken as evidence that cellular energy failure is the cause of the damage. Thus, it appears equally probable that the pathologically enhanced neuronal activity (and metabolic rate) underlies both the cell damage and the perturbed metabolic state. The observed changes in cyclic nucleotides do not appear to bear a causal relationship to the mechanisms of damage.
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PMID:Metabolic changes in cerebral cortex, hippocampus, and cerebellum during sustained bicuculline-induced seizures. 729 97

We produced limbic status epilepticus in rats by injecting a combination of dibutyryl-cAMP (db-cAMP) and ethylenediaminetetraacetic acid (EDTA) into the amygdala (AM). Thirty minutes after intra-AM db-cAMP/EDTA injection, thyrotropin-releasing hormone (TRH) was administered intravenously or intracerebroventricularly. Intravenous TRH (3, 25, 50 mg/kg) produced immediate activation of electroclinical seizures, lasting for 25-45 min. In some animals which showed this seizure activation, complete seizure suppression occurred 55-70 min after the TRH treatment. Similar activation of ictal seizures with delayed seizure suppression was obtained after intracerebroventricular TRH (25, 50 micrograms). The findings suggest that the effects of intravenous TRH are due to its central action and that the use of intravenous TRH is not a promising approach for the treatment of status epilepticus.
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PMID:The effect of thyrotropin-releasing hormone (TRH) on limbic status epilepticus in rats. 780 43

Kainate, a potent excitatory and neurotoxic agent, has also proved useful in studies on other glutamate-driven phenomena, such as neuronal plasticity. Long-term effects of kainate are apparently dependent on its influence on the expression of various genes, including those encoding the AP-1 transcription factor, consisting of proteins belonging to the Fos and Jun families. In our studies we analysed c-fos, fos B, c-jun, jun B and jun D mRNA levels as well as a functional feature of AP-1, its DNA-binding activity, in the rat brain following systemic injection of kainate. Two phases of elevated AP-1 DNA-binding activity were observed in the hippocampus and entorhinal cortex, and were correlated with period of seizures (2 and 6 h after kainate injection) and neuron damage (48-72 h). At 72 h after kainate treatment DNA fragmentation, believed to be diagnostic of apoptotic processes typical of programmed cell death phenomena, was noted. Two and six hours after the treatment, AP-1 consisted predominantly of Fos B, c-Fos, Fra-2 and Jun B, while at 72 h Jun D constituted the major AP-1 component in place of Jun B, and no c-Fos was detected. Only a slight AP-1 increase was seen 24 h after kainate treatment. In the sensory cortex, only the late phase of AP-1 elevation was detected. Contrary to AP-1, no effect of kainate on levels of two other transcription factors, CREB/ATF (cAMP-responsive element binding proteins) and OCT (octamer element DNA-binding activity) was seen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dynamic changes in the composition of the AP-1 transcription factor DNA-binding activity in rat brain following kainate-induced seizures and cell death. 785 19

The c-fos immediate early gene is induced by normal stimuli including light, stress, hyperosmolar solutions, and hormones. Ischemia, hypoxia, seizures, cortical injury, nerve section and other pathological stimuli can also induce c-fos. The induction can occur via increases in intracellular calcium that act through a Ca2+/cAMP element on its promoter, or via trophic and other factors that act through a serum response element (SRE) on its promoter. Several studies show that calcium entry via voltage sensitive calcium channels (VSCCs) is important for inducing c-fos. We have shown that calcium entry via the NMDA receptor is important for induction of c-fos mRNA by glutamate and cAMP in cultured cortical neurons. Moreover, the NMDA receptor appears to regulate translation of c-fos mRNA to Fos protein when cells are stimulated with other types of stimuli including vasoactive intestinal peptide, zinc, and fibroblast growth factor. These results suggest that toxins that elevate intracellular calcium will likely induce the c-fos gene in brain. The heat shock or stress genes are induced by a wide variety of stimuli including heavy metals, heat, oxidative and ischemic stress, prolonged seizures, hypoglycemia, calcium ionophores, and certain toxins. It is believed that denatured proteins stimulate heat shock factors to bind to heat shock elements on the promoters of all heat shock genes to induce gene transcription. We and others have shown that global and focal ischemia induce the hsp70 heat shock gene in brain. Mild ischemia induces hsp70 mRNA and HSP70 protein in neurons only.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in gene expression as an index of neuronal injury: heat shock and the immediate early gene response. 809 Mar 62

A small dose (0.5-1.0 micrograms) of cholera toxin injected into rat hippocampus induced an epileptic focus which discharged intermittently for 7-10 days. Epileptic discharges lasting from 70 ms to 2 min were recorded in vivo through implanted electrodes. The longer bursts could generalize to the neocortex, and occasionally caused motor seizures. The epileptic bursts reached a maximum 3-4 days after injection, and then declined to occasional brief interictal discharges by 9 days. Postmortem histology revealed no evidence of gross pathology or neuronal loss. Hippocampal slices prepared from rats < 8 days after injection of cholera toxin, and maintained in vitro, generated brief spontaneous and evoked epileptic bursts, usually lasting < 1 s. Spontaneous bursts always started in subregion CA3c, and propagated through the pyramidal layer at a mean of 0.18 m/s. Intracellular recordings from CA3 pyramidal layer cells always revealed simultaneous paroxysmal depolarization shifts during epileptic bursts. Epileptic activity, both in vivo and in vitro, required the whole toxin molecule. Injections of either the B subunit or the vehicle solution were not epileptogenic. Therefore binding of the toxin to neuronal membranes, which is mediated by the B subunit, was not sufficient for the epileptogenic effects of cholera toxin. This suggested that the activation of Gs which requires the whole molecule, was necessary. Gs activation is known to stimulate cyclic AMP production, but forskolin, which directly stimulates adenyl cyclase, failed to produce epileptic activity, even though it depressed action potential accommodation and afterhyperpolarizations (AHPs). While further work is required to resolve the basic mechanisms of cholera toxin induced epileptic foci, we propose that they require the activation of Gs, which can enhance Ca2+ currents and modify excitatory synaptic transmission directly. Cyclic AMP induced changes in these properties cannot be excluded. However, cyclic AMP induced reductions in action potential accommodation and AHPs, which are found in cholera toxin foci, may contribute to, but are not sufficient for, epileptogenesis. Cholera toxin differs from the commonly used epileptic agents in that its main action is on G proteins and second messenger systems, rather than on synaptic transmission directly. Furthermore it has a prolonged time course, and does not cause gross pathology. These features combine to make it a distinctive model for epilepsy and neuronal synchronization.
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PMID:Epileptic focus induced by intrahippocampal cholera toxin in rat: time course and properties in vivo and in vitro. 826 12

Levels of cAMP and cGMP in the left and right areas of the rat sensorimotor cortex (SMC) 7 days after pentylenetetrazole kindling (30 days) were determined by radioimmunological assay. It is shown that levels of cyclic nucleotides remained unchanged in rats SMC 7 days after single injection of seizure dose (70 mg/kg) of pentylenetetrazole. Levels of cAMP and cGMP in SMC increased by 2-3 times after 30-day administration of physiological saline as compared to single injection; cortical asymmetry of cAMP and cGMP is absent. Differences in the levels of cyclic nucleotides in sensitive and low-sensitive animals to pentylenetetrazole were not revealed. When kindling was completed cGMP level increased in right SMC and it decreased in left SMC as compared to control animals; cAMP level was unaltered in left and increased in right SMC. The role of cortical asymmetry of cyclic nucleotides development of seizure state is discussed.
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PMID:[Changes in the level of cyclic nucleotides in the left and right sensorimotor areas of the cerebral cortex in rats after corazol-induced kindling]. 831 37

Effects of the cyclic AMP agonists 8-(4-chlorophenylthio)-adenosine 3':5' cyclic monophosphate (CPT-cAMP), dibutyryl cyclic AMP (dbcAMP) and forskolin were studied on extracellular field potentials in rat neocortex slices in vitro. CPT-cAMP and forskolin produced a prolonged enhancement of epileptiform activity resulting from removal of Mg2+ from the bathing medium. DbcAMP had no apparent effect except at high concentrations (1 mM), when it reduced bursting activity. Field potentials observed following electrical stimulation of the corpus callosum in the presence of Mg2+ were enhanced by CPT-cAMP and dbcAMP; however forskolin was without effect. Intracellular recording techniques demonstrated a transient excitatory influence of dbcAMP. The results indicate a role for cyclic AMP in seizure mechanisms.
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PMID:Cyclic AMP analogues increase excitability and enhance epileptiform activity in rat neocortex in vitro. 839 51

The behavioral consequences of metabotropic glutamate receptor (mGluR) activation were investigated following intracerebral administration of the mGluR selective agonists (RS)3,5-dihydroxyphenyl-glycine (3,5-DHPG), (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD), (1R,3S)-1-aminocyclopentane-1,3-dicarboxylate (1R,3S-ACPD), L-2-amino-4-phosphonobutyrate (L-AP4), L-serine-O-phosphate (L-SOP) and (2S,3S,4S)alpha-(carboxycyclopropyl)glycine (L-CCGI) into the thalamus in mice. Injections of 3,5-DHPG, 1S,3R-ACPD and L-CCGI produced dose-dependent increases in limbic seizures with a potency order of 3,5-DHPG = 1S,3R-ACPD > L-CCGI. This effect of 1S,3R-ACPD was stereoselective, since the inactive isomer (1R,3S-ACPD) did not elicit seizure activity. Limbic seizures induced by the phosphoinositide-coupled mGluR subtype selective agonist 3,5-DHPG were attenuated by the mGluR antagonist L-2-amino-3-phosphonopropanoic acid (L-AP3) and dantrolene, inhibitors of mGluR-mediated intracellular calcium mobilization. Interestingly, L-AP4, L-SOP and low doses of L-CCGI also protected against 3,5-DHPG seizures. These data indicate that mGluR agonist-induced limbic seizures in mice are mediated by activation of phosphoinositide-coupled mGluRs. Furthermore, these seizures can be protected against by activation of mGluRs that are negatively-linked to cAMP formation.
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PMID:Induction or protection of limbic seizures in mice by mGluR subtype selective agonists. 853 55


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