Search results for "Seizure."

showing 10 items of 203 documents

Novel Potent Anticonvulsant Agent Containing a Tetrahydroisoquinoline Skeleton

2006

In our studies on the development of new anticonvulsants, we planned the synthesis of N-substituted 1,2,3,4-tetrahydroisoquinolines to explore the structure-activity relationships. All derivatives were evaluated against audiogenic seizures in DBA/2 mice, and the 1-(4'-bromophenyl)-6,7-dimethoxy-2-(piperidin-1-ylacetyl) derivative (26) showed the highest activity with a potency comparable to that of talampanel, the only noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonist in clinical trials as an anticonvulsant agent. Electrophysiological experiments indicated that 26 acts as noncompetitive AMPA receptor modulator.

MaleStereochemistrymedicine.medical_treatmentAMPA receptorIn Vitro TechniquesChemical synthesisMiceStructure-Activity Relationshipchemistry.chemical_compoundPiperidinesSeizuresTetrahydroisoquinolinesAMPADrug DiscoverymedicineAnimalsPotencyReceptors AMPARats WistarTalampanelTetrahydroisoquinolineAntagonistAMPA; Isoquinolines; anticonvulsantsOlfactory PathwaysIsoquinolinesRatsAnticonvulsant AgentAnticonvulsantAcoustic StimulationchemistryMice Inbred DBAMolecular MedicineAnticonvulsants
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Interaction Between Uridine and GABA-Mediated Inhibitory Transmission: Studies In Vivo and In Vitro

1985

Na+-independent [3H]gamma-aminobutyric acid (GABA) binding to membrane preparations from frontal cortex, hippocampus, and thalamus is competitively inhibited by the in vitro addition of a naturally occurring pyrimidinic compound, uridine. Moreover, the intraperitoneal injection of uridine produces a dose-related decrease in the cerebellar content of cyclic GMP and antagonizes its increase elicited by bicuculline. The pyrimidinic compound also shows an antagonism toward bicuculline-induced seizures. The relationship between the anti-convulsant actions of uridine and GABA-mediated inhibitory neurotransmission is discussed in terms of an activation of GABA receptor function by the naturally oc…

MaleSynaptic MembranesNeurotransmissionPharmacologyBicucullineInhibitory postsynaptic potentialHippocampusSynaptic Transmissiongamma-Aminobutyric acidchemistry.chemical_compoundThalamusGABA receptorSeizuresIn vivomedicineAnimalsCyclic GMPUridinegamma-Aminobutyric AcidNeurotransmitter AgentsBicucullineReceptors GABA-AUridineIn vitroFrontal LobeRatsnervous systemNeurologychemistryBiochemistryNeurology (clinical)medicine.drugEpilepsia
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Mutations in SLC13A5 Cause Autosomal-Recessive Epileptic Encephalopathy with Seizure Onset in the First Days of Life

2014

International audience; Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent with an autosomal-recessive inheritance pattern of EE. All seven affected individuals developed subclinical seizures as early as the first day of life, severe epileptic disease, and profound developmental delay with no facial dysmorphism. Given the similarity in clinical presentation in the two families, we hypothesized that the observed phenotype was due …

Male[SDV]Life Sciences [q-bio]Genes Recessive[SDV.GEN] Life Sciences [q-bio]/GeneticsBiologymedicine.disease_causeCompound heterozygosity03 medical and health sciencesEpilepsy0302 clinical medicineSeizures[ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathologyReportmedicineGeneticsRecessiveHumansIctalGenetics(clinical)[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Genetics (clinical)Exome sequencing030304 developmental biologySubclinical infectionGenetics0303 health sciencesMutation[SDV.GEN]Life Sciences [q-bio]/GeneticsBrain Diseases[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology[ SDV ] Life Sciences [q-bio]SymportersGenetic heterogeneityCitrate transportmedicine.disease3. Good healthPedigree[SDV] Life Sciences [q-bio]Genes[ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Mutation[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]Female[ SDV.GEN ] Life Sciences [q-bio]/Genetics030217 neurology & neurosurgery[SDV.MHEP]Life Sciences [q-bio]/Human health and pathologyThe American Journal of Human Genetics
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Lunasin-induced behavioural effects in mice: Focus on the dopaminergic system

2013

The present study for the first time is devoted to identify central effects of synthetic lunasin, a 43 amino acid peptide. A markedly expressed neuroleptic/cataleptic effect was observed at low (0.1-10 nmol/mouse) centrally administered doses in male C57Bl/6 mice. Lunasin considerably reduced the amphetamine hyperlocomotion but weakly apomorphine climbing behaviour. No influence on ketamine and bicuculline effects was observed. Binding assay studies demonstrated modest affinity of lunasin for the dopamine D₁ receptor (Ki=60 ± 15 μM). In a functional assay of cAMP accumulation on live cells lunasin antagonised apomorphine effect on D₁ receptor activation (pEC₅₀=6.1 ± 0.3), but had no effect …

Malemedicine.medical_specialtyApomorphineDopamine AgentsMotor ActivityPharmacologyBicucullineLunasinBehavioral NeuroscienceDopamine receptor D1SeizuresDopamineInternal medicineCyclic AMPmedicineAnimalsHumansGABA-A Receptor AntagonistsAmphetamineReceptorCatalepsyReceptors Dopamine D2ChemistryReceptors Dopamine D1DopaminergicBrainMice Inbred C57BLApomorphineAmphetamineHEK293 CellsEndocrinologyDopamine receptorSoybean ProteinsKetamineExcitatory Amino Acid AntagonistsCentral Nervous System Agentsmedicine.drugBehavioural Brain Research
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Role of Associated Cortical Lesions in Motor Partial Seizures and Lenticulostriate Infarcts

1995

In a population-based study, we evaluated seizures occurring in the first 15 days after strokes among 1,640 consecutive patients who had ischemic (814 infarcts with atheroma and 126 with cardiogenic embolism, 273 lacunar infarcts, 259 transient ischemic attacks) or hemorrhagic stroke (129 supratentorial hematomas and 24 subarachnoïd hemorrhage) on computed tomography (CT) scan. Ninety patients had an epileptic seizure in the first 15 days after stroke onset. Thirteen of the 90 had a lenticulostriate infarct, diagnosed on CT scan, without an apparent ipsilateral cortical ischemic lesion. No lenticulostriate hematoma was observed with seizures. To determine the possible existence of an ipsila…

Malemedicine.medical_specialtyPathologySubarachnoid hemorrhagePopulationFunctional LateralityCentral nervous system diseaseEpilepsyHematomamedicineHumanscardiovascular diseaseseducationStrokeAgedTomography Emission-Computed Single-Photoneducation.field_of_studymedicine.diagnostic_testbusiness.industryElectroencephalographyMagnetic resonance imagingCerebral InfarctionIntracranial Embolism and Thrombosismedicine.diseaseMagnetic Resonance ImagingCerebrovascular DisordersNeurologyIschemic Attack TransientFemaleEpilepsies PartialNeurology (clinical)RadiologyEpileptic seizuremedicine.symptomTomography X-Ray ComputedbusinessEpilepsia
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Epilepsy surgery in children with developmental tumours

2011

AbstractWe report our experience regarding evaluation, surgical treatment and outcomes in a population of 21 children with histopathologically confirmed developmental tumours [nine dysembryoplastic neuroepithelial tumours (DNET), ten gangliogliomas (GG) and two gangliocytomas (GC)] and related epilepsy, analyzing video-EEG, MRI and neuropsychological data, before and after surgery.Most children had focal epilepsy correlating well with lesion location. One patient had epileptic spasms and generalized discharges. Tumours were located in the temporal lobe in 13 patients. Mean age at surgery was 11.16 years. Postsurgical MRI showed residual tumour growth in one DNET. One child had a recurrent g…

Malemedicine.medical_specialtyPediatricsAdolescentPopulationClinical NeurologySeizure outcomeVideo-EEGLow-grade brain tumourGangliogliomaTemporal lobeYoung AdultEpilepsyEpilepsy surgerymedicineHumansEpilepsy surgeryChildeducationNeuropsychological outcomeGangliogliomaRetrospective StudiesDNETeducation.field_of_studyEpilepsybusiness.industryTumour-associated epilepsyInfantGanglioneuromaRetrospective cohort studyGeneral Medicinemedicine.diseaseNeoplasms NeuroepithelialSurgeryEpileptic spasmsNeurologyChild PreschoolFemaleNeurology (clinical)businessFollow-Up StudiesSeizure
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Molecular and functional interactions between tumor necrosis factor-alpha receptors and the glutamatergic system in the mouse hippocampus: Implicatio…

2009

Tumor necrosis factor (TNF)-alpha is a proinflammatory cytokine acting on two distinct receptor subtypes, namely p55 and p75 receptors. TNF-alpha p55 and p75 receptor knockout mice were previously shown to display a decreased or enhanced susceptibility to seizures, respectively, suggesting intrinsic modifications in neuronal excitability. We investigated whether alterations in glutamate system function occur in these naive knockout mice with perturbed cytokine signaling that could explain their different propensity to develop seizures. Using Western blot analysis of hippocampal homogenates, we found that p55(-/-) mice have decreased levels of membrane GluR3 and NR1 glutamate receptor subuni…

Malemedicine.medical_specialtyReceptors Kainic acidMicrodialysisAction PotentialsGlutamic AcidKainate receptorAMPA receptorIn Vitro TechniquesBiologyHippocampusReceptors N-Methyl-D-Aspartateelectrophysiology microiontophoresisSettore BIO/09 - FisiologiaMicechemistry.chemical_compoundGlutamatergicReceptors Kainic AcidSeizuresInternal medicinemedicineAnimalsReceptors Tumor Necrosis Factor Type IIReceptors AMPAMice KnockoutNeuronsInflammationTumor Necrosis Factor-alphaGeneral NeuroscienceGlutamate receptorProtein SubunitsEndocrinologymedicine.anatomical_structureReceptors Glutamatenervous systemchemistryReceptors Tumor Necrosis Factor Type IMetabotropic glutamate receptorAstrocytesCytokinesNMDA receptorNBQXDisease SusceptibilityAstrocyte
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Comparative study of taurine and tauropyrone: GABA receptor binding, mitochondrial processes and behaviour.

2011

Abstract Objectives Taurine, a sulfur-containing amino acid, has high hydrophilicity and is poorly absorbed. Tauropyrone, a taurine-containing 1,4-dihydropyridine derivative, is suggested to have greater activity than taurine owing to improved physicochemical properties that facilitate delivery of the compound to target cells. The aim of this study was to determine whether the 1,4-dihydropyridine moiety in tauropyrone improves the pharmacological efficacy of taurine in vitro and in vivo. Methods The effects of taurine and tauropyrone, as well as of the 1,4-dihydropyridine moiety were compared in in-vitro experiments to determine the binding to GABA receptors and influence on mitochondrial p…

Malemedicine.medical_specialtyTaurineDihydropyridinesGABA receptor bindingTaurinePharmaceutical SciencePharmacologyMotor ActivityBicucullinechemistry.chemical_compoundMiceStructure-Activity RelationshipIn vivoSeizuresInternal medicinemedicineStructure–activity relationshipAnimalsRats WistarReceptorPharmacologychemistry.chemical_classificationMice Inbred ICRDiazepamBehavior AnimalEthanolChemistryGABAA receptorBicucullineReceptors GABA-AAmino acidMitochondriaRatsEndocrinologyMuscle TonusRotarod Performance TestEnergy MetabolismHydrophobic and Hydrophilic Interactionsmedicine.drugProtein BindingThe Journal of pharmacy and pharmacology
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Antiabsence effects of carbenoxolone in two genetic animal models of absence epilepsy (WAG/Rij rats and lh/lh mice).

2005

Carbenoxolone (CBX), the succinyl ester of glycyrrhetinic acid, is an inhibitor of gap junctional intercellular communication. We have tested its possible effects upon two genetic animal models of epilepsy (WAG/Rij rats and lethargic (lh/lh) mice). Systemic administration of CBX was unable to significantly affect the occurrence of absence seizures in WAG/Rij rats. In particular, intravenous (5-40 mg/kg) or intraperitoneal (i.p.; 10-80 mg/kg) administration of CBX was unable to significantly modify the number and duration of spike-wave discharges (SWDs) in WAG/Rij rats, whereas the bilateral microinjection (0.05, 0.1, 0.5 and 1 microg/0.5 microl) of CBX into nucleus reticularis thalami (NRT)…

Malemedicine.medical_specialtyTime FactorsCarbenoxoloneConnexinConnexinsCellular and Molecular Neurosciencechemistry.chemical_compoundEpilepsyMiceMice Neurologic MutantsInternal medicinemedicineAnimalsGlycyrrhizinMicroinjectionGap junctionsPharmacologyDose-Response Relationship DrugGap junctionElectroencephalographyRats Inbred StrainsEpilepsy Carbenoxolone WAG/Rij rat Lethargic mouse Gap junction Connexin Absence seizuresmedicine.diseaseRatsDisease Models AnimalEndocrinologymedicine.anatomical_structurechemistryEpilepsy AbsenceGene Expression RegulationThalamic NucleiSystemic administrationCarbenoxoloneepilepsyAutoradiographyNucleusmedicine.drugGap junctions; Carbenoxolone ; epilepsyNeuropharmacology
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Identification of calcium sensing receptor (CaSR) mRNA-expressing cells in normal and injured rat brain

2009

Calcium sensing receptor (CaSR), isolated for the first time from bovine and human parathyroid, is a G-protein-coupled receptors that has been involved in diverse physiological functions. At present a complete in vivo work on the identification of CaSR mRNA-expressing cells in the adult brain lacks and this investigation was undertaken in order to acquire more information on cell type expressing CaSR mRNA in the rat brain and to analyse for the first time its expression in different experimental models of brain injury. The expression of CaSR mRNAs was found mainly in scattered cells throughout almost all the brain regions. A double labeling analysis showed a colocalization of CaSR mRNA expr…

Malemedicine.medical_specialtyTime FactorsCentral nervous systemHippocampusCell CountSettore BIO/11 - Biologia MolecolareBiologySettore BIO/09 - Fisiologiachemistry.chemical_compoundSeizuresInternal medicineSettore BIO/10 - BiochimicaCaSRmedicineAnimalsRNA MessengerRats WistarIbotenic AcidMolecular BiologyIn Situ HybridizationNeuronsKainic AcidGeneral NeuroscienceDentate gyrusBrainColocalizationImmunohistochemistryRatsOligodendrogliamedicine.anatomical_structureEndocrinologynervous systemchemistryBrain InjuriesNeurogliaNeurology (clinical)Pyramidal cellCaSR; BrainCalcium sensing receptor (CaSR) isolated for the first time from bovine and human parathyroid is a G-protein-coupled receptors that has been involved in diverse physiological functions. At present a complete in vivo work on the identification of CaSR mRNA-expressing cells in the adult brain lacks and this investigation was undertaken in order to acquire more information on cell type expressing CaSR mRNA in the rat brain and to analyse for the first time its expression in different experimental models of brain injury. The expression of CaSR mRNAs was found mainly in scattered cells throughout almost all the brain regions. A double labeling analysis showed a colocalization of CaSR mRNA expression in neurons and oligodendrocytes whereas it was not found expressed both in the microglia and in astrocytes. One week after kainate-induced seizure CaSR was found in the injured CA3 region of the hippocampus and very interestingly it was found up-regulated in the neurons of CA1-CA2 and dentate gyrus. Similarly 1 week following ibotenic acid injection in the hippocampus CaSR mRNA expression was increased in oligodendrocytes both in the lesioned area and in the contralateral CA1-CA3 pyramidal cell layers and dentate gyrus. One week after needle-induced mechanical lesion an increase of labeled cells expressing CaSR mRNA was observed along the needle track. In conclusion the present results contribute to extend available data on cell type-expressing CaSR in normal and injured brain and could spur to understand the role of CaSR in repairing processes of brain injury.Receptors Calcium-SensingIbotenic acidDevelopmental BiologyAstrocyte
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