Modulationofabnormalneuronalcircuitintemporallobeepilepsy

摘要： OBJECTIVETemporallobeepilepsy(TLE)isoneofthemostcommontypesofhumanepilepsy,andtheyareoftenresistanttocurrenttreatments.METHODSByusingoptogenetic,electrophysiological,imagingandpharmacologystrategies,weaimedtoinvestigatetheunderlyingcircuitmechanismofTLEandtriedtodevelopthenovelandefficientapproachtocontrolepilepsy.RESULTS(1)Deepbrainstimulation,especiallylowfrequencystimulation,targetedtheepilepticfocusandtheareasoutsideofthefocus(criticalregionsforseizurespread),suchasentorhinalcortexorsubiculum,reducedseizureseverityinTLE.Itsanti-epilepticeffectistime-windowdependentandpolaritydependent,whichshowsapromisingstrategyfortreatingepilepticseizures.(2)Usinganoptogeneticstrategy,wedemonstratedthatexcitatoryprojectionfromentorhinalcortextohippocampusinstructsthebrain-stimulationtreatmentsofepilepsy.(3)OurdatafromboththeclinicalandexperimentalstudiesfurtherdemonstratedthatadisinhibitoryGABAergicneuron-mediatedmicrocircuitinthesubiculumcontributestosecondarygeneralizedseizuresinTLE.(4)Finally,basedonabnormalsynchronizationoftheelectricalactivityinepilepticcircuit,wedevelopedelectro-responsivehydrogelnanoparticlesmodifiedwithangiopep-2tofacilitatethedeliveryoftheantiepilepticdrugphenytoinsodium,whichgreatlyimprovesthetherapeuticindex.CONCLUSIONOurfindingsmayupdatethecurrentviewofepilepticneuronalnetworksandsuggestpossiblepromisingwaysforepilepsytreatment. ... （共2頁）