2017
In vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence
Hillmer AT, Sandiego CM, Hannestad J, Angarita GA, Kumar A, McGovern EM, Huang Y, O'Connor KC, Carson RE, O'Malley SS, Cosgrove KP. In vivo imaging of translocator protein, a marker of activated microglia, in alcohol dependence. Molecular Psychiatry 2017, 22: 1759-1766. PMID: 28242869, PMCID: PMC5573660, DOI: 10.1038/mp.2017.10.Peer-Reviewed Original ResearchMeSH KeywordsAcetamidesAdultAlcoholismBrainBrain MappingCarbon RadioisotopesCells, CulturedCytokinesFemaleHumansInflammationLipopolysaccharidesMaleMicrogliaMonocytesNeuroimagingPolymorphism, Single NucleotidePositron-Emission TomographyPyridinesRadiopharmaceuticalsReceptors, GABASeverity of Illness IndexConceptsAlcohol-dependent subjectsAlcohol dependenceTSPO levelsTranslocator proteinProinflammatory cytokine interleukin-6Peripheral immune profilePeripheral immune responseCytokine interleukin-6Absence of lipopolysaccharideSubset of subjectsAlcohol use disorderPositron emission tomographyAlcohol-dependent individualsMicroglial activationImmune profileNeuroimmune systemCytokine expressionBrain levelsProinflammatory responseInterleukin-6Healthy controlsInterleukin-8Immune responseLast drinkUse disorders
2015
Brivaracetam, a selective high‐affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action
Nicolas JM, Hannestad J, Holden D, Kervyn S, Nabulsi N, Tytgat D, Huang Y, Chanteux H, Staelens L, Matagne A, Mathy FX, Mercier J, Stockis A, Carson RE, Klitgaard H. Brivaracetam, a selective high‐affinity synaptic vesicle protein 2A (SV2A) ligand with preclinical evidence of high brain permeability and fast onset of action. Epilepsia 2015, 57: 201-209. PMID: 26663401, DOI: 10.1111/epi.13267.Peer-Reviewed Original ResearchConceptsFaster onsetAcute seizuresHigh-affinity synaptic vesicle protein 2A ligandNonhuman primate PET studyAudiogenic seizure miceRapid brain entryOnset of actionSingle oral dosingHigh brain permeabilityBlood-brain barrier permeability (BBBP) valuesPrimate PET studyAudiogenic miceBrain entryCaco-2 cellsSeizure micePreclinical evidenceAntiepileptic drugsSusceptible miceBrain levelsBrain penetrationPreclinical dataBrain kineticsOral dosingSingle dosingClinical studies