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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epilepsy-like convulsive seizures have been induced by cholera toxin administration into the rat amygdaloid complex. Between the 8th and 48th hr after the administration, rhythmic spike discharges (1--3 spikes/sec) were electroencephalographically observed bilaterally in the amygdaloid complexes, and rats exhibited abnormal behaviors such as running, jumping, tail lifting, rearing, vocalization aggressive behavior, facial twitching and increased salivation. During these stages, high voltage spikes were intermittently observed with generalized convulsive seizures. Duration of the seizure was 1--2 min and the incidence was 0--6 times/hr. At 48 hrs after the administration or thereafter, convulsive seizures disappeared and electroencephalographic abnormalities were gradually normalized. Occasional rhythmic spike discharges, however, were observed more than 168 hrs after the administration. Since autoradiographic observations with 125I-labeled cholera toxin revealed that the injected toxin does not spread out at all from the injected site, the use of this toxin seems to be an ideal procedure to produce micro-epileptogenic foci. Cyclic AMP content as well as adenylate cyclase activity in the ipsilateral amygdaloid complex was significantly increased during preconvulsive and convulsive states. The administration of 5 x 10(-8) moles of dibutyryl cyclic AMP through the cannula implanted into the amygdaloid complex also induced behavioral and electroencephalographic abnormalities similar to those found in the cholera toxin-treated animals. These results suggest that cyclic AMP and/or cyclic AMP dependent neuronal mechanisms may play a significant role in the establishment of epileptogenic focus. Possible use of this animal model for the study of anti-epileptic drugs are also suggested.
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PMID:[Cholera toxin induced epileptogenic focus--special reference to cyclic AMP metabolism and epileptogenic focus (author's transl)]. 23 Aug 51

The N-methyl-D-aspartate (NMDA)-sensitive subtype of glutamate receptor, which gates Ca(2+)-permeable ion channels, is known for its role in learning and memory formation, in the induction of long-term potentiation, and also in seizure activity and neurotoxicity. In primary cultures of cerebellar neurons, agonists of NMDA receptors induce a dose-dependent release of [3H]arachidonic acid ([3H]AA), which is potentiated by activation of the glycine-positive modulatory site and inhibited by NMDA receptor antagonists. NMDA receptor-induced [3H]AA release is inhibited by quinacrine and partially depends on the presence of extracellular calcium. The [3H]AA release is not sensitive, however, to pretreatment with pertussis or cholera toxin, which suggests a Ca(2+)-dependent activation of phospholipase A2 not employing G proteins. Pretreatment of cultures with the natural and semisynthetic sphingolipids GT1b and PKS 3, respectively, inhibits NMDA receptor-mediated [3H]AA release. We also demonstrated glutamate-evoked [3H]AA release from rat hippocampal slices, which is NMDA receptor mediated, calcium dependent and sensitive to quinacrine. Arachidonic acid and its metabolites have been shown to play a role as second messengers and to modulate neuronal activity. Moreover, they are thought to act as transsynaptic modulators in the mechanism of NMDA receptor-induced long-term potentiation in the hippocampus. Their role in ischemic brain pathology has also been postulated. Our experiments on cultured cerebellar granule cells, incubated in a Mg(2+)-free medium deprived of glucose and oxygen, demonstrated a time-dependent stimulation of [3H]AA release. This release was inhibited by antagonists of NMDA receptors and by quinacrine. Stimulation of NMDA-sensitive glutamate receptors and the subsequent calcium-mediated activation of phospholipase A2 may play a role in the in vivo release of arachidonic acid during brain ischemia. This hypothesis is supported by the observation that the enhanced level of thromboxane B2 in the gerbil brain after 5 min of global ischemia is reduced by the systemic application of either the NMDA antagonist MK-801 or the ganglioside GM1.
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PMID:NMDA receptor-mediated arachidonic acid release in neurons: role in signal transduction and pathological aspects. 138 78

Injecting 0.5-1.0 microgram of cholera toxin into rat hippocampus induces a chronic epileptic focus which generates interictal discharges and brief epileptic seizures intermittently over the following seven to 10 days. Here we examined the electrophysiological properties of hippocampal slices prepared from these rats three to four days after injection, at the height of the epileptic syndrome. These slices generated epileptic discharges in response to electrical stimulation of afferent pathways. In many cases epileptic discharges occurred spontaneously in the CA3 subregion; these usually lasted < 200 ms, but they could last < 0.6 s. Intracellular recordings from pyramidal layer cells revealed depolarization shifts synchronous with the epileptic field potentials. These depolarization shifts had slow onsets compared with those induced by blocking inhibition with bicuculline (depolarizations started a mean of 57 ms before, and reached 5.2 mV by, the onset of the cholera toxin epileptic field potential, compared with 12 ms and 3.6 mV respectively for 70 microM bicuculline methiodide). Extracellular unit recordings showed that the slow predepolarization seen in the cholera toxin focus was associated with an acceleration of the firing of other pyramidal layer neurons. The epileptic activity in this model cannot be attributed to the loss of synaptic inhibition, because inhibitory postsynaptic potentials could be evoked when the synchronous bursts were blocked by increasing [Ca2+]o from 2 to 8 mM. Observations of monosynaptic inhibitory postsynaptic currents isolated by application of 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione, 50 microM DL-2-amino-5-phosphonovaleric acid and 100-200 microM 3-amino-2-(4-chlorophenyl)-2-hydroxy-propylsulphonic acid showed a small effect of the toxin only on the time course of the inhibitory postsynaptic current. On the other hand, there were significant changes in the intrinsic properties of individual neurons. The membrane potentials of cells in the cholera toxin focus did not differ from those in slices from rats injected with vehicle solution, but their input resistances were significantly increased. Unlike the other cellular changes in this model, the increase in input resistance was not seen in slices exposed acutely to 1 micrograms/ml cholera toxin for 30 min, suggesting there may be morphological changes in the chronic focus. Action potential accommodation and the slow afterhyperpolarization were depressed in both acute and chronic epileptic tissue, indicating impairments of Ca(2+)- and/or voltage-dependent K+ currents, and we conclude that these provide the most likely basis for cholera toxin epileptogenesis.
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PMID:Epileptic focus induced in rat by intrahippocampal cholera toxin: neuronal properties in vitro. 810 80

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

Cholera is an acute intestinal infection caused by Vibrio cholerae 01. When an infected person presents severe dehydration and is not adequately treated, he or she will develop hypovolemic shock and eventually could died. There is scarce information concerning this disease in the Pediatric group. Herein we report on eight cases of Pediatric cholera, in children 17 month to four years of age. Seven patients out of eight were admitted presenting dehydration. Four presenting mild or moderate dehydration and three presenting hypovolemic shock. These three patients were rehydrated by intravenous route and thereafter the hydration was maintained by oral therapy. The outcome was uneventful in six patients. One patient developed abdominal distention probably due to hypopotassemia, and another patient presented hyponatremia and seizures. All the patients recovered within five days after admission.
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PMID:[Cholera in children. A report of 8 cases]. 827 30

Glutamate (Glu) uptake is the primary mechanism for its removal from the synapse. In genetic audiogenic seizures (AGS), Glu uptake is elevated prior to the appearance of seizures. Increased Glu uptake is also observed in synaptosomes from normal mice preincubated with lithium or nitroarginine, an NO synthase inhibitor. Pertussis and cholera toxins cause a marked reduction in Glu uptake. In contrast, neither lithium nor nitroarginine affected Glu uptake by synaptosomes from genetic epileptic mice. Arachidonic acid inhibits Glu uptake, whereas synaptosomes from epileptic mouse brain appear to be more sensitive to arachidonic acid as indicated by a shift of the inhibition curve to the left. These observations are indicative of the possible regulation of Glu uptake by second messengers and its alteration in genetic epilepsy.
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PMID:Possible regulation of high-affinity glutamate uptake in synaptosomes of normal and epileptic mice. 887 51

The therapeutic mechanism of the action of lithium in the treatment of bipolar affective disorder is not known, in spite of a burgeoning number of biochemical studies linking lithium to signal transduction processes. This article reviews a decade of studies examining the behavioural manifestations of manipulating inositol, cyclic adenosine monophosphate (cAMP) and G proteins in rats. Inositol, forskolin, dibutyryl cAMP and pertussis toxin all interacted with lithium when rearing behavior was measured. Lithium potentiated the increase in locomotion induced by injections of cholera toxin into the nucleus accumbens, consistent with the hypothesis that it inactivates inhibitory G proteins. More specific interactions were found between lithium and inositol following cholinergic and serotonergic stimulation. Inositol, but not forskolin, attenuated lithium-pilocarpine seizures and the enhancement of the serotonin syndrome; however, inositol had no effect on lithium-induced attenuation of wet dog shakes following an injection of 5-hydroxytryptophan. Behavioural evidence supports biochemical findings suggesting that lithium's interactions with the phoshphatidyl inositol and cyclic AMP signal transduction systems may be relevant to its therapeutic effects in bipolar disorder. Further research on more specific behaviours may elucidate the relevant pharmacological mechanisms underlying the therapeutic effect of lithium.
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PMID:Interactions of lithium and drugs that affect signal transduction on behaviour in rats. 1052 45

We previously created a transgenic mouse model of comorbid Tourette's syndrome and obsessive-compulsive disorder (TS+OCD), by expressing a neuropotentiating cholera toxin (CT) transgene in a subset of dopamine D1 receptor-expressing (D1+) neurons thought to induce cortical and amygdalar glutamate output. To test glutamate's role in the TS+OCD-like disorder of these transgenic mice (D1CT-7 line), the effects of glutamate receptor-binding drugs on their behavior were examined. MK-801, a non-competitive NMDA receptor antagonist that indirectly stimulates cortical-limbic glutamate output, aggravated a transgene-dependent abnormal behavior (repetitive climbing and leaping) in the D1CT-7 mice at doses insufficient to induce stereotypies, and more readily induced stereotypies and limbic seizure behaviors at high doses. NBQX, a seizure-inhibiting AMPA receptor antagonist, reduced only the MK-801-dependent stereotypic and limbic seizure behavior of D1CT-7 mice, but not their transgene-dependent behaviors. These data imply that TS+OCD-like behavior is mediated by cortical-limbic glutamate, but that AMPA glutamate receptors are not an essential part of this behavioral circuit. Our findings lead to the prediction that the symptoms of human Tourette's syndrome and obsessive-compulsive disorder are elicited by excessive forebrain glutamate output.
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PMID:Glutamatergic drugs exacerbate symptomatic behavior in a transgenic model of comorbid Tourette's syndrome and obsessive-compulsive disorder. 1098 Feb 39

Prenatal morphine exposure on gestation days 11-18 alters bicuculline-induced seizures in rats during development and in adulthood. Adult, morphine-exposed male progeny exhibit an increased latency to bicuculline seizures, which can be reversed by administration of the opioid receptor antagonist naloxone. In chronically morphine-treated adult mice, cholera toxin B (CTX-B) can reverse the effects of chronic morphine administration. Therefore, the present study investigated whether prenatally morphine-exposed rats show a similar response to CTX-B as chronically morphine-treated adult rodents. Prenatally morphine-, saline- and unexposed male progeny were tested for seizure susceptibility with a 7.5-mg/kg intraperitoneal injection of bicuculline in adulthood. CTX-B or saline was injected subcutaneously at 24, 12, and 0.5 h before bicuculline injection. CTX-B decreased the occurrence of bicuculline-induced seizures in both prenatally saline- and morphine-exposed but not unexposed rats. Furthermore, three, but not one, saline injections administered at 12-h intervals prior to bicuculline administration reversed the increase in seizure latency in prenatally morphine-exposed adult males, suggesting an altered responsiveness of the stress system. The present study demonstrates that CTX-B can decrease the occurrence of bicuculline seizures in prenatally stressed rats and that increased seizure latencies in prenatally morphine-exposed male rats may be related to stress responses.
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PMID:Cholera toxin B decreases bicuculline seizures in prenatally morphine- and saline-exposed male rats. 1500 61

Epilepsy-like convulsive seizures have been induced by cholera toxin administration into the rat amygdaloid complex and lateral ventricle. Between the 8th and 48th h following the administration, rhythmic spike discharges (1-3 spikes/s) were electroencephalographically observed bilaterally in the amygdaloid complexes, and rats exhibited abnormal behaviors such as running, jumping, tail lifting, rearing, vocalization, aggressive behavior, facial twitching and increased salivation. During these stages, high voltage spikes were intermittently observed with generalized convulsive seizures. Duration of the seizure was 1-2 min and the incidence was 0-6 times/h. At 48 h after the administration or thereafter, convulsive seizures disappeared and electroencephalographic abnormalities were gradually normalized. Occasional rhythmic spike discharges, however, were observed more than 168 h after the administration. Intraventricularly administered cholera toxin also induced the same type of convulsive seizures. Cyclic AMP content in the rat cerebrum from toxin-treated animals was significantly higher than that found in controls. The present results clearly indicate that cholera toxin administered intraventricularly as well as into the amygdaloid complexes of the rats induces epileptic attack-like convulsive seizures 8-48 h after the administration and this effect of the toxin is most likely to be related to the increase of cerebral cyclic AMP content.
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PMID:Epilepsy-like convulsive seizures induced by cholera toxin administration into amygdaloid complex and lateral ventricle. 2048 42


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