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

C57BL/6Bg mice had silver bead electrodes chronically implanted on the surface of the cortex and had their cortical EEG recorded during audiogenic seizures following ethanol withdrawal. For 7 days, the experimental groups were fed a liquid diet containing 6% v/v ethanol ad lib as the only source of food and water. The control group was fed a similar diet containing an isocaloric amount of sucrose. The cortical EEG's of experimental and control groups before, during, and after treatment were virtually identical. Only the experimental group was susceptible to audiogenic seizures. During audiogenic seizures, the cortical EEG showed no sign of spike waves or paroxysmal activity. This is in contrast to picrotoxin convulsions with these same mice as well as to spontaneous convulsions in animals following ethanol withdrawal. Similar EEG observations have been reported on audiogenic seizures from genetic and acoustically primed susceptibilities. Consequently, we suggest that all audiogenic seizure responses, including those during ethanol withdrawal, are a type of subcortical epilepsy.
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PMID:Electroencephalographic correlates of audiogenic seizures during ethanol withdrawal in mice. 98 61

Alterations of excitant amino acid (EAA) action are implicated in seizure susceptibility in the genetically epilepsy-prone rat (GEPR). The inferior colliculus (IC) is critical for audiogenic seizure (AGS) initiation in the GEPR. The present study observed that bilateral microinjection into the IC of L-canaline, a glutamate synthesis inhibitor, decreased AGS severity in the GEPR and also decreased potassium-evoked release of glutamate from IC slices. Bilateral microinjection of NMDA receptor antagonists, 2-amino-7-phosphonoheptanoate (AP7) or 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonate (CPP) into IC blocked AGS, and an antagonist at non-NMDA EAA receptors, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), also blocked AGS. NMDA receptor antagonists were 5-200 times more effective than CNQX. Microinjection of a non-competitive NMDA receptor antagonist, dizocilpine (MK-801), into IC had little effect except with very high doses. Microinjection of CPP or AP7 into the IC blocked AGS at considerably lower doses as compared to pontine reticular formation (PRF). However, MK-801 attenuated AGS when microinjected into PRF at doses that were ineffective in IC. Systemically administered CPP blocked AGS and significantly reduced IC neuronal firing in the behaving GEPR, suggesting an important action of systemically administered NMDA receptor antagonists on brainstem auditory nuclei critical to AGS. The present results support a critical role for glutamate acting, in part, through NMDA receptors in IC in initiation of AGS.
Epilepsy Res 1992 Nov
PMID:Glutamate in the inferior colliculus plays a critical role in audiogenic seizure initiation. 136 Nov 65

The N-methyl-D-aspartate (NMDA)-preferring glutamate receptor subtype possesses, in addition to the recognition site for glutamate, a binding site for glycine. We report here on the pharmacological properties of 3-(4,6-dichloro-2-carboxyindol-3-yl)-propionic acid (MDL 29,951) and 4-carboxymethylamino-5,7-dichloroquinoline-2-carboxylic acid (MDL 100,748), two novel glycine antagonists of NMDA receptor activation in vitro and in vivo. We have measured in parallel the effects of two previously described glycine antagonists, 7-chlorokynurenic acid and 5,7-dichlorokynurenic acid. All were potent inhibitors of [3H]glycine binding. Ki values (microM) were 0.36 (7-chlorokynurenic acid), 0.08 (5,7-dichlorokynurenic acid), 0.07 (MDL 100,748) and 0.14 (MDL 29,951). MDL 100,748 and MDL 29,951 were approximately 2000-fold selective for the glycine binding site relative to the glutamate recognition sites. All four compounds completely inhibited the use-dependent binding of [3H]N-[1-(2-thienyl) cyclohexyl]-piperidine and were noncompetitive, glycine-reversible inhibitors of both NMDA-induced biochemical and electrophysiological responses in brain slice preparations. A competitive interaction with the glycine binding site was also evident in that MDL 29,951 and MDL 100,748 produced parallel rightward shifts in the glycine requirement for demonstration of NMDA-stimulated elevations in cytosolic calcium in cultured neuronal preparations. The glycine antagonists were potent anticonvulsants after their i.c.v. administration to audiogenic seizure-susceptible DBA/2J mice. Because the compounds chosen encompass a variety of chemical structures, the results indicate that glycine is required for NMDA receptor activation and that bioavailable glycine antagonists may form the basis of a novel therapy for epilepsy.
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PMID:Potent indole- and quinoline-containing N-methyl-D-aspartate antagonists acting at the strychnine-insensitive glycine binding site. 138 5

Parameters were evaluated for the optimum induction of audiogenic seizure susceptibility in Sprague-Dawley (SD) rats by noise exposure. The effect of maturation on this susceptibility was also examined. It was found that SD rats are most inducible between neonatal days 13 and 15 and that susceptibility requires a minimum of 2 days to develop. Noise exposure on day 14 results in universal susceptibility by day 20, but seizure severity is not maximal until days 32-36. Although susceptibility persists at high levels into adulthood, seizures in older rats revert to the wild-running-only type. Seizure latency (from stimulus onset to onset of wild running) becomes increasingly shorter during the prepubescent period (days 16-24) but is stable at older ages. The mean shortness of latency in adult seizures depends somewhat on the age when initial noise exposure occurred; day-14 noise exposures result in seizures with shortest latencies. Ontogenetic comparisons were made of susceptibility in these noise exposure-induced rats, genetically epilepsy prone rats (GEPRs, which are SD substrains)29 and noise exposure-induced Wistar (WI) rats28. It appears that epileptogenesis begins at virtually the same age in all four groups of rats but that considerable differences characterize the absolute severity of seizures and the age dependence of maximum seizure severity among the strains.
Epilepsy Res 1992 Oct
PMID:Noise exposure-induced audiogenic seizure susceptibility in Sprague-Dawley rats. 147 96

Results of previous studies (Pierson, M. and Swann, J., Epilepsia, 32 (1991) 1-9) have demonstrated that exposure of Wistar rats to noise on day 14 results in audiogenic seizure susceptibility. Experiments reported here examined whether unilateral susceptibility could be induced in rats by monaural restriction of this noise exposure. Behavioral attributes of seizures on day 28 were compared in groups that were: binaurally noise-exposed/binaurally tested, binaurally noise-exposed/monaurally tested, monaurally noise-exposed/binaurally tested and monaurally noise-exposed/monaurally tested. Effects of left- and right-ear exposures and tests were assessed separately. Unilateral susceptibility was evident since seizures could be elicited later only by stimulation of the originally noise-exposed ear. Seizures were behaviorally different in monaurally noise-exposed and binaurally noise-exposed animals. Convulsions, directional reversals during running episodes, and relatively short latencies occur only in binaurally noise-exposed rats. These behaviors occur with either monaural or binaural stimulation. Initial, running direction was random in binaurally stimulated/binaurally noise-exposed rats, but was fixed in all other groups depending on which ear was exposed in either sensitization (day 14) or testing (day 28). Right- and left-ear sensitizations or tests resulted in left-directed and right-directed running onsets respectively. Previous studies of the effect of selective CNS lesions in instances of unilateral or bilateral susceptibility have led to the understanding that seizure initiation in unilaterally susceptible animals is mediated by the crossed ascending auditory pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Epilepsy Res 1992 Mar
PMID:Audiogenic seizures in unilaterally sensitized and monaurally stimulated Wistar rats. 156 35

Brain maturation and GABA metabolism are known to play a key role in epileptogenesis. The metabolism of the polyamines (putrescine, spermidine and spermine) is closely linked to the process of brain maturation. Putrescine has been shown to be catabolized to GABA in brain tissue and astrocytes. In order to better understand the importance of glial putrescine transport and metabolism, a model of age-dependent epilepsy was used to study the kinetic properties of [14C]putrescine uptake into cultured astrocytes from normal C57/BL and audiogenic DBA/2 newborn mice, and the subsequent GABA formation. (1) Putrescine uptake exhibited non-Michaelian allosteric kinetics with positive co-operativity (Hill factor = 2), suggesting a physiological importance of putrescine uptake by astrocytes. (2) The Vmax of putrescine uptake was significantly higher in C57/BL astrocytes than in DBA/2J, but the uptake affinity for putrescine was higher in DBA/2J than in C57/BL. (3) Higher K+ concentrations (18 mM) had little effect on putrescine uptake in either strain. (4) Ten-micromolar N-acetylputrescine, the first putrescine metabolite, stimulated putrescine uptake into astrocytes of both strains, but to a different degree: +46% in C57/BL and + 102% in DBA/2J. (5) The specific radioactivity of the GABA formed from labelled putrescine was four times higher in astrocytes from DBA/2J than from C57/BL mice. (6) The molar ratio of glutamate/GABA in the cerebral cortex of the DBA/2J mice was significantly higher during the period of audiogenic seizure susceptibility than in age-matched C57/BL mice. Our results show characteristics of putrescine uptake into astrocytes; we demonstrated distinct kinetic properties between normal and epileptic strains of mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characteristics of putrescine uptake and subsequent GABA formation in primary cultured astrocytes from normal C57BL/6J and epileptic DBA/2J mouse brain cortices. 158 19

Endogenous cerebral prostanoids possess anticonvulsant properties. This study investigates possible age-dependent anomalies of prostanoid synthesis in the brain of seizure-prone DBA/2J (DBA2) mice as compared to sound stimulus-resistant CFLP mice. Irrespective of the age of the animals, a large increase of prostaglandin (PG) D2 and E2 in the brain of CFLP mice was observed in response to pentylenetetrazol (PTZ)-, or electroshock (ES)-induced seizures. Significantly less PGD2 and PGE2 was formed in the brain of DBA2 mice at day 21 after birth when subjected to PTZ or ES convulsions. At 42 days of age, however, this deficit of cerebral PGD2 synthesis in DBA2 mice disappeared concomitantly with the age-related decrease in audiogenic seizure (AS) susceptibility, whereas the deficit of PGE2 formation persisted. These results suggest that a deficiency of cerebral PGD2 synthesis may be one of the factors responsible for the AS susceptibility of the DBA2 mice. In contrast to PTZ or ES convulsions, acoustically induced seizures of the DBA2 mice were not accompanied by cerebral prostanoid synthesis. This supports the view that the pathways involved in AS are different from those involved in PTZ or ES models of epilepsy.
Epilepsy Res 1990 Mar
PMID:Differential prostaglandin formation induced by convulsions in the brain of mice susceptible (DBA/2J) and resistant (CFLP) to acoustic stimulation. 232 14

The genetically epilepsy-prone (GEP) rat is susceptible to seizure induction by acoustic stimuli. The inferior colliculus (IC) has been implicated as being critically important in audiogenic seizure susceptibility based on lesion, electrical stimulation, and focal implantation experiments. The current study determined that GEP rats were most susceptible to seizure induction by pure tone bursts at 100 dB at a frequency of 12 kHz. IC neurons in the GEP rat exhibited a significantly elevated incidence of a particular response pattern at 12 kHz and at characteristic frequency. This pattern consisted of a peak at the beginning and end of the stimulus (onset-offset response). This response pattern only occurred with high intensity stimuli approximating those which induce seizures and may represent an afterdischarge phenomenon. The response threshold was significantly elevated and tuning characteristics were also significantly altered in IC neurons of GEP rats as compared to normal IC neurons. The latter two findings may be related to the deficit of hearing which is reported in the GEP rat. The increased incidence of onset-offset responses may be due to a decreased efficacy of inhibition in the GEP rat neurons as compared to normal rat neurons.
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PMID:Neuronal response abnormalities in the inferior colliculus of the genetically epilepsy-prone rat. 241 87

Two markers for noradrenergic neurons: 1) desmethylimipramine sensitive norepinephrine (NE) uptake and 2) dopamine beta-hydroxylase activity were compared in various brain regions of normal and genetically epilepsy-prone rats (GEPR). These studies were designed to characterize further the nature of the noradrenergic deficit in GEPRs, which has been described as a reduction in steady-state NE levels. The high affinity (desmethylimipramine-sensitive) uptake of 3H-NE into crude synaptosomes was found to be significantly reduced in widespread areas of the GEPR forebrain including cortex, hippocampus, amygdala and hypothalamus. GEPRs also displayed a reduced uptake of 3H-NE in synaptosomes from the inferior colliculus, a structure that has been implicated in the audiogenic seizure, but other regions of the brain stem (reticular formation, cochlear nucleus, cerebellum) failed to reveal abnormalities in NE uptake. Reductions in dopamine beta-hydroxylase activity seemed to parallel the reductions in NE uptake regionally (except for the caudate nucleus), and both deficits (uptake and dopamine beta-hydroxylase) were similar in magnitude to the decrements in steady-state NE levels reported previously. The present findings therefore support the concept that there is a reduction in the number of noradrenergic terminals in most structures receiving noradrenergic innervations in the GEPR brain.
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PMID:Regional brain abnormalities in norepinephrine uptake and dopamine beta-hydroxylase activity in the genetically epilepsy-prone rat. 270 32

The purpose of this paper was to study the relationship between different neurotransmitter systems and seizure susceptibility in Mongolian gerbils with genetically determined epilepsy. In these animals, generalized tonic-clonic seizures were induced by stimulation with a blast of compressed air. A variety of drugs that specifically manipulate inhibitory or excitatory neurotransmitter systems proved capable of dose dependently blocking these seizures, i.e., the anticholinergic drug biperiden (ED50 12 mg/kg i.p.), the excitatory amino acid antagonist (+/-)-2-amino-7-phosphonoheptanoic acid (120 mg/kg), the gamma-aminobutyric acid (GABA) agonists muscimol (0.66 mg/kg), 4,5,6,7-tetrahydroisoxazolo(5,4-c) pyridine-3-ol (1.3 mg/kg), progabide (50 mg/kg) and its acidic metabolite SL 75102 (45 mg/kg), the GABA aminotransferase inhibitors aminooxyacetic acid (0.9 mg/kg), gamma-acetylenic GABA (2.1 mg/kg) and ethanolamine-O-sulfate (1000 mg/kg), the GABA uptake inhibitor (-)-nipecotic acid ethyl ester (21 mg/kg), the dopamine agonist apomorphine (approximately 5 mg/kg), the dopamine precursor 3,4-dihydroxy-L-phenylalanine (34 mg/kg), and the alpha-adrenoceptor agonists clonidine (0.38 mg/kg) and xylazine (approximately 10 mg/kg). The anticonvulsant effect of 3,4-dihydroxyl-L-phenylalanine was not significantly affected by pretreatment with the dopamine-beta-hydroxylase inhibitors disulfiram and diethyldithiocarbamate, thus strongly indicating that 3,4-dihydroxyl-L-phenylalanine was acting through increase in dopamine rather than noradrenaline levels in the brain. The (+)-isomer of nipecotic acid ethyl ester, the glycineamide derivative milacemide, the indirect 5-hydroxytryptamine agonist fenfluramine and the 5-hydroxytryptamine antagonist ketanserin exerted no anticonvulsant action. The 5-hydroxytryptamine precursor L-5-hydroxytryptophan and the dopamine agonist lisuride were only weakly active but exerted pronounced side effects in the animals. Weak anticonvulsant effects were also determined for atropine, the noradrenaline precursor DL-threo-3,4-dihydroxyphenylserine and the excitatory amino acid antagonist (+/-)-2-amino-5-phosphonopentanoic acid. Comparison of anticonvulsant potencies of the various drugs in gerbils with potencies reported in other genetic animal models of epilepsy, such as audiogenic seizure-susceptible mice, indicated that drugs that increase GABA and dopamine levels in the brain are strikingly more effective in gerbils than in other species in blocking generalized seizures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Influence of pharmacological manipulation of inhibitory and excitatory neurotransmitter systems on seizure behavior in the Mongolian gerbil. 285 79


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