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Query: UMLS:C0596131 (audiogenic seizure)
 315 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic animal models of epilepsy comprise genetically predisposed animal species in which seizures either occur spontaneously or in response to sensory stimulation. The major advantage of these naturally occurring epilepsies in animals as models of human epilepsy is that they simulate the clinical situation more closely than any other experimental epilepsy. Models with idiopathic spontaneous recurrent seizures are epileptic dogs, tottering mice, and rats with spike-wave absence (petit mal) seizures. In dogs, the most common seizure type are generalized tonic-clonic (grand mal) seizures. Recent epidemiological and antiepileptic drug efficacy studies strongly suggest that epileptic dogs offer a valuable model for human grand mal epilepsy. In tottering mice, two types of spontaneous recurrent seizures occur: spike-wave absence seizures and focal motor seizures. Both types differ in sensitivity to common antiepileptic drugs, which closely resembles the absence and focal types of epilepsy in humans. Spontaneously recurrent spike-wave absence seizures in rats can be selectively blocked by drugs effective in petit mal (absence) epilepsy in man, demonstrating the validity of this new petit mal model for anticonvulsant drug screening. Models with reflex seizures comprise photosensitive baboons (Papio papio) and fowl, audiogenic seizure susceptible mice and rats, and gerbils with seizures in response to different sensory stimuli. With respect to seizure types and drug efficacies in these species, rats and chickens may represent suitable models for grand mal epilepsy, whereas baboons offer a useful model of photomyoclonic seizures. Gerbils can be subdivided into animals with minor (myoclonic) and major (mostly generalized tonic-clonic) seizures, which respond differently to antiepileptic drugs and seem to provide interesting models for petit mal and grand mal epilepsy in man. In conclusion, the data summarized in this review emphasize that genetic animal models of epilepsy offer unique approaches to the evaluation of antiepileptic drugs used or usable in man.
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PMID:Genetic animal models of epilepsy as a unique resource for the evaluation of anticonvulsant drugs. A review. 643 66

The major neutral and acidic cerebellar lipids were studied in audiogenic seizure (AGS)-resistant C57BL/6 (B6) and AGS-susceptible DBA/2J (D2) mice. These cerebellar lipids were also studied in the D2.B6- Iasb congenic mice and in the B6D2F1 hybrids that are mostly AGS resistant. Except for the Iasb gene, which inhibits AGS susceptibility, the D2.B6- Iasb congenic mice are genetically similar to the D2 mice. Because subtle abnormalities in the chemical structure of membranes may underlie epilepsy, we wanted to determine if AGS susceptibility was associated with abnormalities in the distribution of cerebellar lipids. A new method for the analysis of total brain lipids was used in this study. Slight, but significant, differences were found between the B6 and D2 strains for the concentrations (microgram/100 mg wet weight) of sphingomyelin, phosphatidylcholine, and cerebrosides. However, these differences may not be associated with differences in AGS susceptibility since the concentrations of these lipids in the AGS-resistant D2.B6- Iasb and B6D2F1 mice were more similar to the D2 than the B6 concentrations. The expression of Iasb is not responsible for the lipid differences found between the B6 and D2 mice.
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PMID:Genetic analysis of cerebellar lipids in mice susceptible to audiogenic seizures. 672 80

Felbamate (2-phenyl-1,3-propanediol dicarbamate) is a novel anticonvulsant substance whose mechanism of action is not clearly understood. The present investigation examined its ability to modulate the strychnine-insensitive glycine receptor associated with the N-methyl-D-aspartate (NMDA) receptor. Felbamate decreased the magnitude of glycine (100 microM)-enhanced NMDA (100 microM)-induced intracellular calcium ([Ca2+]i) transients in mouse cerebellar granule cells which had been loaded with the Ca(2+)-sensitive fluorescent probe indo-1 acetoxymethyl ester (indo-1/AM). This effect of felbamate was concentration dependent, with a maximal effect observed at 300 microM (65 +/- 4% of control). In the Frings audiogenic seizure-susceptible mouse model of reflex epilepsy, the glycine agonist D-serine (150 nmol, i.c.v.) completely blocked the anticonvulsant activity of a maximally effective dose of felbamate (19 mg/kg, i.p.). This effect of D-serine could be reversed by increasing the administered dose of felbamate to 29 mg/kg. Furthermore, administration of D-serine (300 nmol, i.c.v.) to felbamate-treated Frings mice produced a parallel right shift in felbamate's anticonvulsant dose-response curve (ED50s: 9.4 mg/kg for felbamate vs. 17.7 mg/kg for felbamate + D-serine). The results obtained in this investigation suggest that the ability of felbamate to modulate the strychnine-insensitive glycine receptor may be physiologically and behaviorally relevant to its anticonvulsant mechanism of action.
Epilepsy Res 1995 Jan
PMID:Felbamate modulates the strychnine-insensitive glycine receptor. 771 59

Previous studies using single-unit recording techniques have shown that the inferior colliculus is critical for audiogenic seizure initiation in genetically epilepsy-prone rats (GEPR). In order to investigate cellular abnormalities that may be important in causing audiogenic seizure susceptibility, intracellular recordings were made from neurons of inferior colliculus dorsal cortex (ICd) in a GEPR variety that exhibits severe audiogenic seizures (GEPR-9). GEPR neuronal membrane and synaptic properties were compared to those of normal Sprague-Dawley rats (SD), the strain from which GEPR were derived. We found six electrophysiological differences between GEPR and normal SD ICd neurons, all of which could promote seizures in GEPR. (1) Input resistance was higher in GEPR than in normal ICd neurons. (2) Threshold for repetitive action potential firing was closer to resting membrane potential in GEPR ICd neurons. (3) GEPR neurons showed faster repetitive spike firing than normal SD neurons. (4) Anode break spikes occurred at the offset of a hyperpolarizing pulse more often in GEPR than in normal SD neurons. (5) Stimulation of the commissure of the inferior colliculus caused synaptic paired pulse inhibition in normal ICd neurons, but paired pulse facilitation was always observed in GEPR neurons. (6) In GEPR, a large epileptiform depolarizing event could be elicited by strong electrical stimulation of the commissure of the inferior colliculus. In normal SD rats, similar epileptiform activity was seen only after application of bicuculline or NMDA. Our results suggest that both abnormal neuronal membrane properties and altered synaptic transmission are likely to contribute to seizure predisposition and audiogenic seizure initiation in GEPR.
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PMID:Inferior colliculus neuronal membrane and synaptic properties in genetically epilepsy-prone rats. 782 Jun 92

The anticonvulsant properties of a mixture of non-esterified alpha-linolenic acid and linoleic acid with a ratio of 1:4 (SR-3) were evaluated in four rat models of epileptic seizures: (1) i.p. injection of a single convulsant dose (50 mg/kg or 100 mg/kg) of pentylenetetrazol; (2) repeated subconvulsant doses of pentylenetetrazol; (3) cortical irritation by intraventricular administration of iron chloride (FeCl3); and (4) audiogenic seizure-prone preparation created by repeated pretreatment with p-cresol. Treatment with SR-3 (about 40 mg/kg i.p.) for a period of 3 weeks prior to challenge was found effective in each of these experimental models and caused up to a 22-fold increase in latency to major motor seizures, up to 84% reduction in the number of rats with seizures, and up to a 97% reduction in the duration of seizures. It is postulated that the anticonvulsant effects of SR-3 may be related to its stabilization of neuronal membranes. SR-3 should be evaluated further as a treatment for epilepsy.
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PMID:Essential fatty acid preparation (SR-3) raises the seizure threshold in rats. 791 28

Tiagabine is a new anticonvulsant drug that blocks the uptake of GABA, prolonging the action of this inhibitory transmitter. In the present study the effects of systemically administered tiagabine [30 mg/kg, ip (ED50)] were examined on audiogenic seizure (AGS) severity and neuronal firing in the inferior colliculus (IC) in the freely moving genetically epilepsy-prone rat (GEPR-9). The IC is known to be critical to AGS initiation. The effects of focal microinjection of tiagabine into the IC were also examined. Bilateral focal microinjection of tiagabine into the IC significantly reduced seizure severity in the GEPR-9. Systemically administered tiagabine also produced a significant reduction in seizure severity in the GEPR-9. Tiagabine produced a reduction in IC (central nucleus) neuronal firing, which was significant only at high acoustic intensities (90-105 dB), concomitant with the considerable reduction in seizure severity. These data are consistent with enhancement by tiagabine of gamma-aminobutyric acid (GABA)-mediated inhibition in IC, which is most prominent at high acoustic intensities. The time course of the reduction in neuronal firing of IC neurons paralleled the reduction in seizure severity. Previous studies have shown that two forms of GABA-mediated inhibition (intensity-induced and offset inhibition) in IC neurons are most prominent at high stimulus intensities, which are required to induce AGS. The blockade of GABA uptake by tiagabine may act to inhibit audiogenic seizures, in part, by intensifying these naturally occurring forms of acoustically evoked inhibition in inferior colliculus neurons.
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PMID:Blockade of GABA uptake with tiagabine inhibits audiogenic seizures and reduces neuronal firing in the inferior colliculus of the genetically epilepsy-prone rat. 792 22

Genetically epilepsy-prone rats (GEPR) are an animal model of generalized motor seizures. The underlying causes of the predisposition to seizures in GEPR have not been fully determined. The brainstem auditory system is critical for audiogenic seizures in GEPR, and neurophysiological abnormalities have been observed in these areas, but recent evidence suggests that non-auditory brain areas may also be abnormal. This may account for the lowered threshold in GEPR for various non-audiogenic seizures. Because the normal responses of the hippocampal Schaffer collateral/CA1 synapse are relatively well understood, we studied single and repetitive synaptic responses in hippocampal slices of GEPR in vitro. Our hypothesis was that altered excitatory or inhibitory synaptic transmission may contribute to GEPR non-audiogenic seizure predisposition. We recorded extracellular EPSPs, population spikes, and afferent volleys in hippocampal area CA1, and compared GEPR responses to those of Sprague-Dawley (SD) rats, the strain from which GEPR were derived. GEPR responses to single synaptic stimuli were not significantly different from SD. The second of a pair of closely spaced EPSPs or population spikes was larger in both GEPR and SD (paired pulse facilitation), but the magnitude of population spike facilitation was significantly increased in GEPR. Short trains of four stimuli caused inhibition of population spike firing in SD, an effect that was much reduced in GEPR. When SD slices were treated with bicuculline, a GABAA receptor antagonist, enhanced paired pulse facilitation and loss of inhibition during trains of stimuli were seen, similar to the patterns seen in GEPR.(ABSTRACT TRUNCATED AT 250 WORDS)
Epilepsy Res 1994 Jun
PMID:Loss of synaptic inhibition during repetitive stimulation in genetically epilepsy-prone rats (GEPR). 795 41

Previous studies have implicated a decreased efficacy of GABA as an important defect subserving the audiogenic seizures of the genetically epilepsy-prone rat (GEPR-9). The inferior colliculus (IC) is a critical site for audiogenic seizure (AGS) initiation, and the pontine reticular formation (PRF) is implicated in the propagation of AGS and in other generalized seizure models. The present study observed that microinjection of baclofen, a GABA-B receptor agonist, into IC protects against AGS, and blockade of the breakdown of endogenous GABA by gabaculine, a GABA transaminase inhibitor, increased GABA levels and blocked AGS susceptibility in the GEPR-9. Microinjection of baclofen or gabaculine into the PRF reduced AGS severity, but the doses required were considerably greater and the degree of anticonvulsant effect was less. Uptake of [3H]GABA into GEPR-9 synaptosomes from the IC is significantly increased as compared to normal, which could contribute to the diminished effectiveness of GABA in the GEPR-9. Previous studies indicate that GABA-A receptor agonists block AGS with IC microinjection, and recent data indicate that blockade of GABA uptake in this nucleus significantly reduced AGS severity. These data taken together strongly support the critical importance of the defect in GABA function in the IC in modulating susceptibility to audiogenic seizure initiation in the GEPR-9.
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PMID:GABA in the inferior colliculus plays a critical role in control of audiogenic seizures. 800 65

The genetically epilepsy-prone rat (GEPR) and other mammals with genetically based epilepsy are characterized by an innate predisposition to seizures evoked by a wide variety of stimuli (including those of endogenous origin). The present investigation was undertaken to identify the anatomical location of the noradrenergic terminal fields responsible for regulation of seizure predisposition. In this study, audiogenic seizure severity was used as the index of seizure predisposition. The effect of widespread destruction of noradrenergic terminal fields was compared with the effect of destroying regionally distinct terminal fields. These lesions were produced by microinfusion of 6-hydroxydopamine (6-OHDA) into the locus ceruleus, the A1 noradrenergic area, the noradrenergic dorsal bundle, the cerebellar peduncles and spinal intrathecal space. Selective depletion of norepinephrine in the forebrain, the cerebellum, or the spinal cord failed to alter audiogenic seizure severity. An increase in seizure severity was always associated with marked depletion of norepinephrine in the midbrain excluding the inferior colliculus. Also a significant correlation existed between the seizure intensification and reduction of norepinephrine in this structure in all instances where a seizure intensification was observed. An association of seizure intensification also existed in all cases except one with depletion in the pons/medulla. The present findings support the hypothesis that the noradrenergic terminal fields of the midbrain excluding the inferior colliculus are determinants of seizure predisposition. Inasmuch as audiogenic seizures are a type of brainstem seizure, the present findings do not a priori pertain to the noradrenergic regulation of forebrain seizures.
Epilepsy Res 1994 May
PMID:Noradrenergic terminal fields as determinants of seizure predisposition in GEPR-3s: a neuroanatomic assessment with intracerebral microinjections of 6-hydroxydopamine. 808 52

Fluoxetine (15 mg/kg i.p.) decreased the audiogenic seizure intensity in 33% of severe seizure genetically epilepsy-prone rats (GEPR-9s). 5-Hydroxytryptophan (5-HTP, 12.5 mg/kg i.p.) produced no anticonvulsant effect in GEPR-9s. When GEPR-9s were treated with a combination of these two drugs, the combination treatment decreased the audiogenic seizure intensity in 83% of the animals tested. Brain microdialysis studies showed that the same combination of 5-HTP and fluoxetine also produced a marked potentiation of the increase in the extracellular serotonin concentration in the thalamus of freely-moving GEPR-9s when compared with administration of either drug alone. A negative correlation between audiogenic seizure intensity and extracellular serotonin concentration existed after either fluoxetine alone or the combination treatment. No significant changes in extracellular norepinephrine concentrations were observed after the combination treatment. These results coupled with our earlier reports strongly suggest that a serotonergic mechanism is involved in the anticonvulsant effects of fluoxetine in GEPRs.
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PMID:Evidence that a serotonergic mechanism is involved in the anticonvulsant effect of fluoxetine in genetically epilepsy-prone rats. 814 89


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