Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596131 (audiogenic seizure)
 315 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The N-4,4-diphenyl-3-butenyl derivative of the glial selective gamma-aminobutyric acid (GABA) uptake inhibitor 4,5,6,7-tetrahydroisoxazolo [4,5-c]pyridin-3-ol (N-DPB-THPO), was tested for its ability to block sound-induced seizures in the audiogenic seizure-susceptible Frings mouse model of epilepsy. Following intracerebroventricular (i.c.v.) administration, N-DPB-THPO blocked tonic hindlimb extension in a dose- and time-dependent manner. At the doses tested no gross behavioral effects were noted.
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PMID:Anticonvulsant activity of the gamma-aminobutyric acid uptake inhibitor N-4,4-diphenyl-3-butenyl-4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol . 831 39

Excitant amino acids are implicated in audiogenic seizure (AGS) susceptibility in the genetically epilepsy-prone rat (GEPR). In the present study systemic administration of NMDA receptor antagonists significantly decreased AGS severity in the GEPR. Systemic administration of the competitive NMDA antagonists 3-((+-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP) and 2-amino-7-phosphonoheptanoic acid and the non-competitive antagonist dizocilpine (MK-801) were effectively anticonvulsant in the GEPR. The inferior colliculus is the most critical nucleus for AGS initiation in the GEPR and an excitant amino acid is implicated as an important excitatory transmitter in inferior colliculus neurons. Systemically administered CPP significantly reduced inferior colliculus neuronal firing in the normal behaving rat and the GEPR concurrently with blockade of AGS and this effect occurred at nearly all sound intensities tested. Systemic administration of MK-801, while effective in blocking AGS, produced no consistent change in inferior colliculus neuronal firing, which is consistent with its very low potency in blocking AGS with bilateral microinjection into the inferior colliculus. These findings suggest that an important action of competitive, but not noncompetitive, NMDA antagonists is on brain stem auditory nuclei, especially the inferior colliculus, that are critical to AGS. MK-801 appears to exert its anticonvulsant effects in AGS network sites beyond the inferior colliculus. These findings and recent inferior colliculus slice studies suggest that NMDA receptors in inferior colliculus may have quantitatively different properties from those in other brain regions. These differences in NMDA receptor function in inferior colliculus may reflect NMDA receptor heterogeneity observed in binding studies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Noncompetitive and competitive NMDA antagonists exert anticonvulsant effects by actions on different sites within the neuronal network for audiogenic seizures. 843 60

Previous studies have shown significantly greater GABA levels and numbers of GABAergic neurons in the central nucleus of the inferior colliculus (ICCN) of genetically epilepsy-prone rats (GEPR-9s). In the present study, in situ hybridization and emulsion autoradiographic techniques were used to determine whether there are also elevated numbers of ICCN cells that contain the 67-kD form of mRNA for the GABA synthesizing enzyme, glutamate decarboxylase (GAD), in GEPR-9s as compared to normal Sprague-Dawley (SD) rats. Hybridization with a 35S-labeled RNA probe complementary to a span of monkey GAD mRNA labeled cells throughout the brain including the ICCN. Labeled cells in the ICCN appeared to be of different sizes that corresponded with previous descriptions of GABAergic neurons from immunocytochemical studies. In the GEPR-9s, a larger number of GAD67 cRNA labeled neurons was observed in the ICCN as compared to SD rats. The external nucleus of the inferior colliculus was also found to contain significantly greater numbers of GAD67 cRNA labeled neurons whereas in the frontal cortex, a region of the brain that is not required for audiogenic seizure activity in GEPR-9s, there were no significant differences in hybridization between GEPR-9s and SD rats. Interestingly, within the superficial layers of the superior colliculus there was a higher density of hybridization in GEPR-9s than in SD rats indicating higher levels of GAD expression.(ABSTRACT TRUNCATED AT 250 WORDS)
Epilepsy Res 1993 Feb
PMID:The inferior colliculus of GEPRs contains greater numbers of cells that express glutamate decarboxylase (GAD67) mRNA. 845 48

The seizure susceptibility of carbonic anhydrase II (CA) deficient mice and their normal littermates was determined and compared. In flurothyl-induced seizures, CA deficient mice displayed longer latencies to the onset of both clonic and tonic-clonic seizures. In pentylenetetrazole-induced seizures mutant mice exhibited a lower incidence of clonic seizures than did their normal littermates. Acetazolamide (a CA blocker) was used for the pretreatment of normal mice to compare them to CA deficient littermates. The pretreated mice displayed a lower incidence of flurothyl-induced tonic-clonic seizures and of both types of pentylenetetrazole seizures. The attempts to elicit audiogenic seizure did not reveal any difference between normal and mutant littermates. However, when the mice were primed by a loud sound during the critical period and retested for audiogenic seizures again at age 1.5 months, the CA deficient mice displayed a significantly lower incidence of seizures. The similarity between the anticonvulsant action of CA deficiency and the anticonvulsant action of acetazolamide suggests an important role of CA in seizures. The exact mechanism of anticonvulsant action by CA inhibition, however, remains to be elucidated.
Epilepsy Res 1993 Feb
PMID:Reduced susceptibility to seizures in carbonic anhydrase II deficient mutant mice. 845 49

Pharmacological and neurochemical evidence indicates that brain noradrenergic systems play an important role in the determination of audiogenic seizure severity in genetically epilepsy-prone rats (GEPRs). In earlier studies, intracerebroventricular (ICV) injections of norepinephrine suppressed convulsions in a now extinct moderate seizure GEPR colony. Also, ICV noradrenergic agonists are known to produce dose-related anticonvulsant effects in the extant moderate seizure GEPRs (GEPR-3s). The present experiments were undertaken to determine whether ICV norepinephrine also suppresses audiogenic seizures in the extant GEPR-3s and in the severe seizure genetically epilepsy-prone rats (GEPR-9s). Injections of norepinephrine or vehicle were made into the lateral ventricle through implanted guides. GEPR-9s were pretreated systemically either with the monoamine oxidase inhibitor pargyline or with saline. GEPR-3s received no pretreatment. In pargyline pretreated GEPR-9s, seizure severity fell and the fraction of animals exhibiting an anticonvulsant response increased progressively as the dose of norepinephrine was increased. In saline pretreated GEPR-9s, the anticonvulsant dose response curve for norepinephrine was shifted to a higher dose range. Accordingly, the anticonvulsant dose50 for norepinephrine was significantly greater in saline pretreated GEPR-9s than in pargyline pretreated animals. Moreover, the dose required to produce the anticonvulsant effect in GEPR-9s was approximately 10 fold greater than in the earlier studies in the extinct moderate seizure GEPRs. Also, the current experiment with extent GEPR-3s, showed that ICV norepinephrine was anticonvulsant in the same dose that was effective in the extinct colony of moderate seizure GEPRs. In general terms, these observations provide additional evidence that noradrenergic influences are anticonvulsant in the GEPR. The neurobiological factors responsible for reduced responsiveness of the GEPR-9 are presently unknown.
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PMID:Anticonvulsant effects of intracerebroventricularly administered norepinephrine are potentiated in the presence of monoamine oxidase inhibition in severe seizure genetically epilepsy-prone rats (GEPR-9s). 846 44

Forebrain seizures were kindled in rats by daily electrical stimulation of the amygdala. Genetically epilepsy-prone rats scoring 9 (GEPR-9s) on the seizure severity scale during audiogenic seizure (AGS) screening ("brainstem seizure-experienced") required fewer stimulations to achieve fully kindled seizures (forelimb clonus with rearing and falling) than control rats. AGS-naive GEPR-9s required an intermediate number of stimulations, indicating a role for both genetic predisposition and previous acoustically evoked brainstem seizure experience. Other forebrain kindling indices such as afterdischarge threshold/duration and seizure latency/duration also involved genetic as well as phenotypic (previous seizure experience) factors. In most GEPR-9s in both groups, severe brainstem seizures occurred after forebrain stimulation. The occurrence of brainstem seizures had a random nature and was not related to the sequence of kindling-dependent forebrain seizure progression. The lack of a difference in the occurrence of brainstem seizures between seizure-experienced and AGS-naive GEPR-9s suggest that genetic predisposition is the major factor in forebrain seizure-induced activation of brainstem seizure circuitry. This brainstem seizure activity appears to model pertinent aspects of secondary generalization observed in human partial seizures.
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PMID:Amygdala kindling of forebrain seizures and the occurrence of brainstem seizures in genetically epilepsy-prone rats. 863 30

Previous studies have shown that widespread depletion of brain 5-hydroxytryptamine (5-HT, serotonin) exacerbates audiogenic seizures in genetically epilepsy-prone rats (GEPRs), while elevations in brain 5-HT attenuate these seizures. However, the location of the central nervous system site(s) at which 5-HT exerts its anticonvulsant action on audiogenic seizures, remains unknown. The substantia nigra has been shown to exert modulatory actions over both brainstem and forebrain driven seizures in normal rats, and receives a rich serotonergic innervation. The present study was designed to determine if 5-HT exerts its modulatory effect on audiogenic seizures by an action in the substantia nigra. Microinfusion of 5,7-dihydroxytryptamine (4 micrograms/0.25 microliter bilateral) into the substantia nigra of GEPRs which display a moderate seizure (GEPR-3s) failed to alter the audiogenic seizure. Consistent with these findings, microinfusions of fluoxetine-HCl into the substantia nigra of severe seizure GEPRs (GEPR-9s) failed to alter any aspect of the audiogenic seizure. This effect was observed when fluoxetine was infused alone, or in combination with systemic administration of 5-hydroxytryptophan (75 mg/kg, i.p.). The present findings argue against a modulatory role of nigral 5-HT on audiogenic seizures in GEPRs.
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PMID:Neither intranigral fluoxetine nor 5,7-dihydroxytryptamine alter audiogenic seizures in genetically epilepsy-prone rats. 890 Oct 11

The nucleus reticularis pontis oralis (RPO) is necessary for the expression of tonic hindlimb extension (THE) in maximal electroshock seizures (MES) of rats. Previous work in this laboratory has demonstrated that focal RPO microinfusion of NMDA antagonists inhibited THE while focal RPO microinfusion of NMDA induced convulsive activity similar to the audiogenic seizure response of rats. The purpose of the present study was to identify other receptors in the RPO that influence THE or induce convulsive activity. Bilateral microinfusion of bicuculline had no effect on the THE component of MES except when the bicuculline induced wild-running convulsions in which case the subsequent THE response to the MES stimulus was inhibited. The GABAergic agents muscimol, baclofen or 2-hydroxysaclofen neither altered the THE response nor induced convulsions. In addition, bilateral RPO microinfusion of the clinically effective antiepileptic drugs phenytoin, phenobarbital, valproate, ethosuximide or felbamate had no effect on the THE component of MES. These results indicate that the role of GABAergic receptors in the anticonvulsant activity mediated by the RPO is not prominent and that the RPO is unlikely to be the site of antiepileptic drug action in MES.
Epilepsy Res 1996 Nov
PMID:The effect on maximal electroshock seizures induced by GABA agents and antiepileptic drugs microinfused into the nucleus reticularis pontis oralis. 895 12

Remacemide hydrochloride is currently undergoing clinical trials for use as an anticonvulsant agent in the treatment of epilepsy. It is considered that the desglycinyl metabolite (FPL 12495AA) of the parent compound accounts for the majority of the anticonvulsant activity. In this study we have investigated the effects of FPL 12495AA on electrical activity in the cortical wedges prepared from audiogenic seizure-prone DBA/2 mice. FPL 12495AA at varying concentrations (50-200 microM) significantly reduced both the spontaneous depolarizations (IC50 102 microM) and the associated afterpotentials (IC50 50 microM) which are characteristic in this preparation under magnesium-free conditions. The compound also concentration-dependently reduced N-methyl-D-aspartate (NMDA)-induced depolarizations of the tissue (IC50 43 microM) and the antagonism by FPL 12494AA was not overcome by increasing NMDA concentrations. FPL 12495AA had no effect on (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-induced depolarizations. The results suggest that FPL 12495AA has a specific antagonistic effect on the NMDA receptor complex possibly through non-competitive inhibition at the phenycyclidine site in the ion channel. Such an action could contribute to its anticonvulsant properties.
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PMID:The effect of the desglycinyl metabolite of remacemide on cortical wedges prepared from DBA/2 mice. 899 98

Audiogenic seizures, a model of brainstem epilepsy, are characterized by a tonic phase (sustained muscular contraction fixing the limbs in a flexed or extended position) associated with a short cortical electroencephalogram flattening. When sound-susceptible rats are exposed to repeated acoustic stimulations, kindled audiogenic seizures, characterized by a clonic phase (facial and forelimb repetitive jerks) associated with cortical spike-waves, progressively appear, suggesting that repetition of brainstem seizures causes a propagation of the epileptic discharge toward the forebrain. In order to determine the structures through which this propagation occurs, four kinds of experiments were performed in non-epileptic rats and in sound-susceptible rats exposed to single or repeated sound stimulations. The following results were obtained: (I) Electrical amygdalar kindling was similar in non-epileptic and naive-susceptible rats, but was facilitated in sound-susceptible rats submitted to 40 acoustic stimulations and presenting kindled audiogenic seizures. (2) Audiogenic seizures induced an increase in [(14)C]2-deoxyglucose concentration in the amygdala after a single seizure, and in the amygdala, hippocampus and perirhinal and piriform cortices after a kindled audiogenic seizure. (3) A single audiogenic seizure induced the expression of c-Fos protein mainly in the auditory nuclei. A few cells were stained in the amygdala. After 5-10 audiogenic seizures, a clear staining appeared in the amygdala, and perirhinal and piriform cortices. The hippocampus expressed c-Fos later, after 40 audiogenic seizures. (4) Injection of lidocaine into the amygdala did not modify single audiogenic seizures, but suppressed myoclonias and cortical spike-waves of kindled audiogenic seizures. Similar deactivation of the hippocampus failed to modify kindled audiogenic seizures. Taken together, these data indicate a critical role for the amygdala in the spread of audiogenic seizures from brainstem to forebrain.
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PMID:The amygdala is critical for seizure propagation from brainstem to forebrain. 913 Jul 79


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