Neurobiology of seizure predisposition in the genetically epilepsy-prone rat

Dailey, John W.; Reigel, Charles E.; Mishra, P. K.; Jobe, Phillip C.

doi:10.1016/0920-1211(89)90063-6

Cited by 142 publications

(64 citation statements)

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“…In this strain, epilepsy is genetically determined, even though the exact mechanisms underlying the development of the disorder remain incompletely understood [24,27]. A nonspecific propensity for generalized seizures, regardless of the eliciting stimuli, enhances the value of this strain of rats as a model in the study of gene-linked generalized epilepsy.…”

Section: Introductionmentioning

confidence: 99%

“…Various neurotransmitters have been involved in the genesis of seizures in this animal model, and particular attention has been focused on both gamma-aminobutyric acid (GABA) and glutamate [24,33,34]. Additionally, drugs decreasing noradrenergic or serotonergic transmission increase convulsion intensity in GEPRs, while drugs increasing serotonergic or noradrenergic function decrease convulsion intensity [27,[35][36][37]. Finally, noradrenergic deficiencies exist in GEPRs that have experienced multiple sound-induced seizures, as well as in GEPRs that have been protected from seizureprovoking stimuli [27,38].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, drugs decreasing noradrenergic or serotonergic transmission increase convulsion intensity in GEPRs, while drugs increasing serotonergic or noradrenergic function decrease convulsion intensity [27,[35][36][37]. Finally, noradrenergic deficiencies exist in GEPRs that have experienced multiple sound-induced seizures, as well as in GEPRs that have been protected from seizureprovoking stimuli [27,38].…”

Section: Introductionmentioning

confidence: 99%

“…Genetically epilepsy-prone rats (GEPRs) represent an established animal model to study the pathophysiology of seizures and to screen potential new antiepileptic drugs [24][25][26][27][28][29][30][31]. In this strain, epilepsy is genetically determined, even though the exact mechanisms underlying the development of the disorder remain incompletely understood [24,27].…”

Section: Introductionmentioning

confidence: 99%

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Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

et al. 2015

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Antipsychotic drugs (APs) are of great benefit in several psychiatric disorders, but they can be associated with various adverse effects, including seizures. To investigate the effects of chronic antipsychotic treatment on seizure susceptibility in genetically epilepsy-prone rats, some APs were administered for 7 weeks, and seizure susceptibility (audiogenic seizures) was evaluated once a week during treatment and for 5 weeks after drug withdrawal. Furthermore, acute and subchronic (5-day treatment) effects were also measured. Rats received haloperidol (0.2-1.0 mg/kg), clozapine (1-5 mg/kg), risperidone (0.03-0.50 mg/kg), quetiapine (2-10 mg/kg), aripriprazole (0.2-1.0 mg/kg), and olanzapine (0.13-0.66 mg/kg), and tested according to treatment duration. Acute administration of APs had no effect on seizures, whereas, after regular treatment, aripiprazole reduced seizure severity; haloperidol had no effects and all other APs increased seizure severity. In chronically treated rats, clozapine showed the most marked proconvulsant effects, followed by risperidone and olanzapine. Quetiapine and haloperidol had only modest effects, and aripiprazole was anticonvulsant. Finally, the proconvulsant effects lasted at least 2-3 weeks after treatment suspension; for aripiprazole, a proconvulsant rebound effect was observed. Taken together, these results indicate and confirm that APs might have the potential to increase the severity of audiogenic seizures but that aripiprazole may exert anticonvulsant effects. The use of APs in patients, particularly in patients with epilepsy, should be monitored for seizure occurrence, including during the time after cessation of therapy. Further studies will determine whether aripiprazole really has a potential as an anticonvulsant drug and might also be clinically relevant for epileptic patients with psychiatric comorbidities.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

et al. 2015

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“…Although there are several single-locus mutants in mice including dilute Eerhal, tottering, stargazer, and lethargic, electrophysiologic analyses of the cellular mechanisms (2)(3)(4) of epileptogenesis have been conducted largely in rats. Nearly all rat models including the genetically epilepsy-prone rat (GEPR,5,6), the genetic absence epilepsy rats from Strasbourg (GAERS, 7), the WAG/Rij rat (8), and the spontaneous epileptic rat (SER,9) are polygenic, and in both the GAERS and WAG/Rij, seizures begin in the fourth week of life or later. Recently a single-locus mutation in rats, tish, was reported to result in heterotopias and spontaneous convulsive seizures; however, the developmental course of these seizures has yet to be reported (10).…”

mentioning

confidence: 99%

Characterization of Seizures in the Flathead Rat: A New Genetic Model of Epilepsy in Early Postnatal Development

Sarkisian¹,

Rattan²,

D’Mello³

et al. 1999

Epilepsia

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Summary:Purpose: Disorders in normal central nervous system (CNS) development are often associated with epilepsy. This report characterizes seizures in a novel genetic model of developmental epilepsy, the Flathead (FH) rat.Methods: Animals (n = 76) ages PO-22 were monitored for clinical and electrographic seizure activity. The effects of various AEDs on seizure frequency and duration also were assessed: phenobarbital (PB; 40 mgkg), valproate (VPA; 400 mgkg), or ethosuximide (ESM; 600 mgkg).Results: FHs display episodes of behavior characterized by whole-body tremor, strub tail, alternating forelimb clonus, and complete tonus. EEG recordings from neocortex reveal that FH seizures are bilateral and begin around P7. Seizures occur at a frequency of approximately six per hour from P7 to P18 and the average duration of seizures increases through development. PB, VPA, and ESM failed to prevent seizures; however, PB significantly increased the interval of seizures but had no effects on the duration of seizures, whereas VPA decreased the duration of seizures and not the interval.Conclusions: Seizures in FH rats occur at a constant and high frequency through a defined period in early postnatal development, and these seizures are not completely blocked by high doses of PB, VPA, or ESM. Because FH is a single-locus mutant displaying a highly regular pattern of seizure activity, it is an ideal model for examining the process of epileptogenesis in the developing brain, evaluating new AED therapies, and determining the identity of a gene essential to the normal development of cortical excitability. Key Words: SeizuresAutosomal recessive-Microcephaly-Antiepileptic drugsDevelopment-Cerebral cortex .Genetic models of epilepsy are powerful tools in understanding the mechanisms of epileptogenesis. Animal genetic models can be effectively used to (a) evaluate new and established antiepileptic (AED) therapy on spontaneously generated seizures, (b) define the timing and distribution of excitability changes leading to seizures, and (c) identify genes essential to normal neuronal excitability (1). There are currently several genetic models of epilepsy in rodents; however, there are virtually no models in rats that are single-locus mutations with generalized convulsive seizures in early postnatal development. Although there are several single-locus mutants in mice including dilute Eerhal, tottering, stargazer, and lethargic, electrophysiologic analyses of the cellular mechanisms (2-4) of epileptogenesis have been conducted largely in rats. Nearly all rat models including the genetically epilepsy-prone rat (GEPR,5,6), the genetic absence epilepsy rats from Strasbourg (GAERS, 7), the WAG/Rij rat (8), and the spontaneous epileptic rat (SER, 9) are polygenic, and in both the GAERS and WAG/Rij, seizures begin in the fourth week of life or later. Recently a single-locus mutation in rats, tish, was reported to result in heterotopias and spontaneous convulsive seizures; however, the developmental course of these seizures has yet to be reported ...

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Imaging epileptogenic tubers in children with tuberous sclerosis complex usingα‐[¹¹C]Methyl‐L‐tryptophan positron emission tomography

Chugani

Muzik

et al. 1998

Annals of Neurology

249

128

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Several reports have indicated that cortical resection is effective in alleviating intractable epilepsy in children with tuberous sclerosis complex (TSC). Because of the multitude of cortical lesions, however, identifying the epileptogenic tuber(s) is difficult and often requires invasive intracranial electroencephalographic (EEG) monitoring. As increased concentrations of serotonin and serotonin-immunoreactive processes have been reported in resected human epileptic cortex, we used alpha-[11C]methyl-L-tryptophan ([11C]AMT) positron emission tomography (PET) to test the hypothesis that serotonin synthesis is increased interictally in epileptogenic tubers in patients with TSC. Nine children with TSC and epilepsy, aged 1 to 9 years (mean, 4 years 1 month), were studied. All children underwent scalp video-EEG monitoring, PET scans of glucose metabolism and serotonin synthesis, and EEG monitoring during both PET studies. [11C]AMT scans were coregistered with magnetic resonance imaging and with glucose metabolism scans. Whereas glucose metabolism PET showed multifocal cortical hypometabolism corresponding to the locations of tubers in all 9 children, [11C]AMT uptake was increased in one tuber (n=3), two tubers (n=3), three tubers (n=1), and four tubers (n=1) in 8 of the 9 children. All other tubers showed decreased [11C]AMT uptake. Ictal EEG data available in 8 children showed seizure onset corresponding to foci of increased [11C]AMT uptake in 4 children (including 2 with intracranial EEG recordings). In 2 children, ictal EEG was nonlocalizing, and in 1 child there was discordance between the region of increased [11C]AMT uptake and the region of ictal onset on EEG. The only child whose [11C]AMT scan showed no regions of increased uptake had a left frontal seizure focus on EEG; however, at the time of his [11C]AMT PET scan, his seizures had come under control. [11C]AMT PET may be a powerful tool in differentiating between epileptogenic and nonepileptogenic tubers in patients with TSC.

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Neurobiology of seizure predisposition in the genetically epilepsy-prone rat

Cited by 142 publications

References 26 publications

Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

Characterization of Seizures in the Flathead Rat: A New Genetic Model of Epilepsy in Early Postnatal Development

Imaging epileptogenic tubers in children with tuberous sclerosis complex usingα‐[¹¹C]Methyl‐L‐tryptophan positron emission tomography

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Neurobiology of seizure predisposition in the genetically epilepsy-prone rat

Cited by 142 publications

References 26 publications

Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

Comparative Analysis of the Treatment of Chronic Antipsychotic Drugs on Epileptic Susceptibility in Genetically Epilepsy-prone Rats

Characterization of Seizures in the Flathead Rat: A New Genetic Model of Epilepsy in Early Postnatal Development

Imaging epileptogenic tubers in children with tuberous sclerosis complex usingα‐[11C]Methyl‐L‐tryptophan positron emission tomography

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Product

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Imaging epileptogenic tubers in children with tuberous sclerosis complex usingα‐[¹¹C]Methyl‐L‐tryptophan positron emission tomography