Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present experiments investigated if dorsal pontine tissue obtained from 16-day postconception rat fetuses and stereotaxically transplanted into the dorsal hippocampus or third ventricle of genetically epilepsy-prone rats (GEPRs) would alter the expression of audiogenic seizures. Of eight GEPR-9s receiving pontine-tissue grafts bilaterally into the dorsal hippocampus, none showed any reduction in AGS severity. In contrast, three of five GEPR-9s receiving grafts into the third ventricle eventually displayed a decreased seizure severity following transplantation. Of five GEPR-3s receiving transplants into the hippocampus, one animal showed a gradual and significant reduction in seizure severity after transplantation. Tyrosine-hydroxylase (TH) immunohistochemistry showed that transplanted tissue contained abundant TH-immunoreactive profiles including perikarya and fibers. The results of these preliminary studies suggest that the GEPR model of epilepsy may be useful in studying the corrective potential of neurotransplants.
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PMID:Intracerebral grafting of fetal dorsal pons in genetically epilepsy-prone rats: effects on audiogenic-induced seizures. 167 95

Cannabidiol (CBD) exhibits anticonvulsant activity in experimental animals and in man. As part of a structure-activity study, analogs were prepared wherein the terpene unit, the aryl unit, and/or the side chain were modified. Thus, several pinenyl and carenyl derivatives, aryl ethers and acetates, and a variety of 1",1"-dialkylhexyl and 1",1"-dialkylheptyl analogs were synthesized. The compounds were evaluated for anti-convulsant activity in seizure susceptible (AGS) rats and for neurotoxicity in the rat rotorod (ROT) test. Comparisons of stereoisomers of CBD and several analogs revealed a general lack of stereoselectivity for anticonvulsant and other CNS properties of this class of compounds.
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PMID:Structure-anticonvulsant activity relationships of cannabidiol analogs. 312 80

Non-responsive progeny from Sprague-Dawley derived rats genetically susceptible to sound-induced (audiogenic) convulsions (AGS-negative) and non-responsive progeny from Sprague-Dawley derived rats not gentically susceptible to audiogenic convulsions (SD-negative) were subjected to a seven-day treatment regimen of sodium barbital. 125 mg/kg, every 12 hours. This represents a lower dose and shorter treatment period than that normally used in this laboratory to induce barbiturate dependence in rats. Animals were subjected to a 115 dB sound stimulus 38 hours following the last dose of sodium barbital. SD-negative rats did not become susceptible to sound-induced convulsions, but AGS-negative rats did experience convulsions when exposed to the sound stimulus during withdrawal. These results are consistent with the hypothesis that rats generally referred to as "audiogenic" may actually suffer from differences which result in an increase of susceptibility to seizures induced by any of several means.
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PMID:Increased susceptibility of audiogenic rats to barbital withdrawal convulsions. 668 82

The epilepsies are a heterogeneous collection of seizure disorders with a lifetime expectancy risk rate of 2-4%. A convergence of evidence indicates that heritable factors contribute significantly to seizure susceptibility. Genetically epilepsy-prone rodent strains have been frequently used to examine the effect of genetic factors on seizure susceptibility. The most extensively studied of these have been strains that are susceptible to sound-induced convulsions (audiogenic seizures, or AGSs). Early observations of the AGS phenomenon were made in the laboratory of Dr. Ivan Pavlov; in the course of appetite-conditioning experiments in mice, the loud bell used to signal food presentation unexpectedly produced seizures in some animals. In 1947, DBA/2 (D2) mice were found to exhibit a genetic susceptibility to AGSs stimulated by a doorbell mounted in an iron tub. Since this discovery, AGSs have been among the most intensively studied phenotypes in behavioural genetics. Although several genetic loci confer susceptibility to AGSs, the corresponding genes have not been cloned. We report that null mutant mice lacking serotonin 5-HT2C receptors are extremely susceptible to AGSs. The onset of susceptibility is between two and three months of age, with complete penetrance in adult animals. AGS-induced immediate early gene expression indicates that AGSs are subcortical phenomena in auditory circuits. This AGS syndrome is the first produced by a known genetic defect; it provides a robust model for the examination of serotoninergic mechanisms in epilepsy.
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PMID:Sound-induced seizures in serotonin 5-HT2c receptor mutant mice. 924 Dec 79

The mechanisms and brain circuitry that render genetically epilepsy-prone rats (GEPRs) susceptible to acoustically induced seizures are not completely known. The present study explores the neuroanatomy of acoustically induced seizures by immunohistochemical analysis of the proto-oncoprotein fos after intense acoustic stimulation (AS) with and without seizures. Acoustic stimulation induced tonic convulsions in GEPR-9s, but not in control rats. Locations of brain nuclei showing fos-like immunoreactive (FLI) neurons following AS with and without seizures were mapped. Semiquantitative methods were used to compare FLI neuron numerical densities in AS control rats and GEPRs. Many brain areas exhibited profound FLI in AS control rats and GEPRs. Unexpectedly, the cochlear nuclei and the central nucleus of the inferior colliculi (ICc), both of which are requisite for AGS initiation, exhibited a diminished fos expression in animals having seizures compared to AS controls. In contrast, GEPRs displayed a significant increase in FLI neurons within the dorsal cortex of the IC (ICd) compared to AS controls. This finding may suggest a seizure-related amplification of the auditory signal between the ICc and the ICd. Other nuclei, known to be involved in auditory transmission (i.e., superior olivary complex; trapezoid nucleus; dorsal nucleus of the lateral lemniscus, DNLL), did not show differential FLI densities between seizure and AS control animals. In contrast, seizure-induced FLI was observed in many nonauditory brain nuclei. Of particular interest was the identification of an intensely labeled nucleus in the GEPR. This nucleus resides in the most posterior and dorsal-lateral part of the pedunculopontine tegmental nucleus-pars compacta (PPTn-pc) immediately adjacent to the DNLL and extends posteriorly into the superior lateral subnucleus of the lateral parabrachial area (SLPBn). Therefore, we have tentatively termed this nucleus the PPSLPBn. The PPSLPBn lies in a region previously described as a mesencephalic locomotor region and a suspected functional involvement of this nucleus in display of seizure activity is under investigation. Other brain stem nuclei showing differential fos expression between GEPRs and AS control rats are also described.
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PMID:Seizures and proto-oncogene expression of fos in the brain of adult genetically epilepsy-prone rats. 927 43

Regional brain amino acid levels have been determined by HPLC, following microwave fixation, in seizure susceptible (University of Arizona, Audiogenic seizure-susceptible, AGS) and non-seizure susceptible Sprague-Dawley rats. Glutamine content is significantly lower in cerebellum, hippocampus, striatum, substantia nigra, colliculi and brain stem reticular formation in AGS rats. Aspartate levels are also reduced (by 33%) in striatum, substantia nigra and inferior colliculus, and glutamate is reduced in hippocampus and striatum. Other differences include a slight fall in taurine content (in striatum) and an increase in GABA content (in hippocampus). Measurements of amino acid levels in AGS rats during the course of a seizure induced by sound show increases in aspartate and glutamate content in some brain regions (including the inferior colliculus). Potassium-evoked [(3)H] d-aspartate release from hippocampal slices did not differ between the seizure-susceptible and seizure-resistant rat strains. It is proposed (i) that changes in the level and turnover of excitatory amino acid transmitters in AGS rats occur as a consequence of a primary biochemical defect that probably involves impaired neuronal membrane transport, and (ii) that altered function in excitatory synapses in the inferior colliculus, substantia nigra and reticular formation contributes importantly to the seizure susceptibility.
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PMID:Brain regional amino acid levels in seizure susceptible rats: Changes related to sound-induced seizures. 2049 57

The effects of metoprine, an inhibitor of histamine N-methyltransferase, on open field activity and brain regional histamine (HA) content were examined in rats with mixed, absence and audiogenic, epilepsy (WAG/Rij-AGS), rats with audiogenic epilepsy (Wistar-AGS) and in non-epileptic control rats (Wistar-nAGS). HA content was increased by metoprine (20mg/kg, i.p.) in the cortex, striatum, thalamus, hypothalamus and hippocampus of the rats from all three tested groups. However, WAG/Rij rats showed a lower rate of metoprine-induced HA accumulation in the striatum and thalamus than Wistar rats. For the open field test, the main effect of metoprine (20mg/kg, i.p.) was a general increase of locomotor activity although distinctive features, such as hyperlocomotion and exaggerated sniffing, were characteristic for the epileptic rats (WAG/Rij-AGS and Wistar-AGS, respectively). Individual rats from all the groups showed stereotyped behavior of shuttle type and head bobbing. Electroencephalographic data obtained in WAG/Rij-AGS rats confirmed that metoprine-induced behavioral activation was accompanied by suppression of spike-wave discharges, the main hallmark of absence seizures. Taken together, these results show that inhibition of the histamine catabolism may induce motor activation of particular patterns in epileptic rats and provoke stereotyped behavior.
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PMID:Metoprine induced behavioral modifications and brain regional histamine increase in WAG/Rij and Wistar rats. 2250 55

Epilepsy is defined as a disorder of the brain characterized by an enduring predisposition to experience epileptic seizures and the neurobiological, cognitive, psychological, and social difficulties relating to the condition. An epileptic spasm (ES) is a type of seizure characterized by clusters of short contractions involving axial muscles and proximal segments. However, the precise mechanism of ESs remains unknown. Despite the potential of magnetoencephalography (MEG) as a tool for investigating the neurophysiological mechanism of ESs, it has been difficult to use this methodology due to magnetic artifacts attributable to patient movement. We report on an 8-year-old girl suffering from intractable epileptic spasms from the age of 7 months. She was diagnosed with possible Aicardi syndrome [corrected] (AGS), characterized by the triad of callosal agenesis, infantile spasms, and chorioretinal lacunae. She is now intellectually delayed and suffers from intractable ES. We used both MEG and electroencephalography to investigate her epilepsy. The recording captured two series of spasm clusters. Spikes were clearly identified with MEG in about four-fifths of all spasms but were identified poorly or not at all in the remainder. MEG findings support previous studies that used intracranial electrodes to analyze patients with ESs and that showed variability in ES-associated spikes in terms of manner of cortical involvement and magnitude. Given the limitations of intracranial electrodes, such as sampling restrictions and invasiveness, MEG may be a helpful tool for non-invasively investigating the unique pathophysiological profile of focal-onset ESs.
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PMID:Magnetoencephalography reveals a unique neurophysiological profile of focal-onset epileptic spasms. 2334 9

Genetic animal models for convulsive, non-convulsive and mixed types of generalized epilepsies were used to establish putative histaminergic brain sites involved in the control of different types of epilepsy. Age matched rats of the KM strain (audiogenic seizures, AGS), WAG/Rij strain (absence seizures) and the WAG/Rij-AGS substrain (mixed model) were compared with a control group of Wistar rats on regional binding densities of H1 histamine receptors. Coronal slices of adult brains of the four groups were labeled with 3H pyrilamine, an antagonist of H1 histamine receptor and density of receptors was quantified with image analyses. All three groups of epileptic rats showed an increase in the density of H1 histamine receptor binding in the frontal motor cortex and interposed nucleus of cerebellum compared to the non-epileptic control group. Audiogenic epilepsy was characterized by increased H1 histamine receptor density in the frontal cortical and hippocampal regions, and in two midbrain (interpedunculus and lateral vestibular) nuclei. Absence epilepsy was characterized by a decrease in substantia nigra pars compacta, while the mixed model showed an elevation of H1 histamine receptor binding density in limbic regions such as the shell of the nucleus accumbens and the ventral tegmental area. It can be concluded that common changes in H1 histamine receptors can be found in genetic epilepsy models irrespective of the seizure type, and that each type of generalized epilepsy has its own pattern of H1 histamine receptor changes. It is speculated that H1 histamine receptors play a role in the brain's endogenous epilepsy control system.
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PMID:H1 histamine receptor densities are increased in brain regions of rats with genetically generalized epilepsies. 2759 91

Acoustically evoked seizures (e.g., audiogenic seizures or AGS) are common in models of inherited epilepsy and occur in a variety of species including rat, mouse, and hamster. Two models that have been particularly well studied are the genetically epilepsy prone rat (GEPR-3) and the Wistar Audiogenic Rat (WAR) strains. Acute and repeated AGS, as well as comorbid conditions, displays a close phenotypic overlap in these models. Whether these similarities arise from convergent or divergent structural changes in the brain remains unknown. Here, we examined the brain structure of Sprague Dawley (SD) and Wistar (WIS) rats, and quantified changes in the GEPR-3 and WAR, respectively. Brains from adult, male rats of each strain (n=8-10 per group) were collected, fixed, and embedded in agar and imaged using a 7 tesla Bruker MRI. Post-acquisition analysis included voxel-based morphometry (VBM), diffusion tensor imaging (DTI), and manual volumetric tracing. In the VBM analysis, GEPR-3 displayed volumetric changes in brainstem structures known to be engaged by AGS (e.g., superior and inferior colliculus, periaqueductal grey) and in forebrain structures (e.g., striatum, septum, nucleus accumbens). WAR displayed volumetric changes in superior colliculus, and a broader set of limbic regions (e.g., hippocampus, amygdala/piriform cortex). The only area of significant overlap in the two strains was the midline cerebellum: both GEPR-3 and WAR showed decreased volume compared to their control strains. In the DTI analysis, GEPR-3 displayed decreased fractional anisotropy (FA) in the corpus callosum, posterior commissure and commissure of the inferior colliculus (IC). WAR displayed increased FA only in the commissure of IC. These data provide a biological basis for further comparative and mechanistic studies in the GEPR-3 and WAR models, as well as provide additional insight into commonalities in the pathways underlying AGS susceptibility and behavioral comorbidity.
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PMID:Divergent brain changes in two audiogenic rat strains: A voxel-based morphometry and diffusion tensor imaging comparison of the genetically epilepsy prone rat (GEPR-3) and the Wistar Audiogenic Rat (WAR). 2927 30


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