69
0
Full metadata record
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | 김승현 | - |
| dc.contributor.author | 김영철 | - |
| dc.date.accessioned | 2024-03-01T07:32:20Z | - |
| dc.date.available | 2024-03-01T07:32:20Z | - |
| dc.date.issued | 2018.2 | - |
| dc.identifier.uri | http://hanyang.dcollection.net/common/orgView/200000432228 | en_US |
| dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/188216 | - |
| dc.description.abstract | ExcessiveactivationofPoly(ADP-ribose)polymerase-1(PARP-1)afterischemicstrokeisknowntodevelopneuronalapoptosis,necrosisandinflammation.ThepresentstudyinvestigatedinvitroandinvivoneuroprotectiveeffectsofanovelPARP-1inhibitor,JPI-289.TheinhibitorstronglyinhibitedPARP-1activity(IC50=18.5nM)andcellularPARlevel(IC50=10.7nM).Inratcorticalneuronalcells,JPI-289didnotaffectcellviabilityupto1mMasshownintrypanbluestaining(TBS)andlactatedehydrogenase(LDH)assays.Inoxygenglucosedeprived(OGD)ratcorticalneuron,treatmentofJPI-289attenuatedPARPactivityandrestoredATPandNAD+levels.JPI-289treatmentintheOGDmodelshoweddecrementofapoptosis-associatedmoleculesincludingapoptosis-inducingfactor(AIF),cytochrome-Candcleavedcaspase-3.AftertheevaluationofJPI-289invitromodel,weinvestigatedtheneuroprotectiveeffectsofJPI-289inratpermanentandtransientstrokemodels.Intransientmiddlecerebralarteryocclusion(MCAO)modelinrats,JPI-289treatmentshowedsignificantreductionofinfarctedareaofbrain,whichwasmaximalatthedoseof10mg/kgupto36%reduction.Thetherapeutictimewindowwas8hoursforreductionofischemicvolumeupto29%.Moreover,numberofapoptoticcellsdecreasedby56%comparedtocontrol.WhenmodelwastwitchedtopermanentMCAOmodelinrats,JPI-289treatmentsignificantlyreducedinfarctedvolumeupto20%atthedoseof40mg/kg,andimprovedbehavioralsocre.AlongwithstableandsafedataofnovelPARP-1inhibitor,JPI-289onpharmacokineticsandtoxicology,itseffectivenessonischemicstrokemodelsandmodesofactionmechanismssuggestthatJPI-289couldbeapotentialtherapeuticagentforthetreatmentofacuteischemicstroke. | - |
| dc.publisher | 한양대학교 | - |
| dc.title | TherapeuticeffectsofanovelPARP-1inhibitor,JPI-289,inmodelsofacuteischemicstroke | - |
| dc.title.alternative | 급성허혈성뇌졸중에서새로운PARP-1억제제(JPI-289)의치료효과 | - |
| dc.type | Theses | - |
| dc.contributor.googleauthor | 김영철 | - |
| dc.contributor.alternativeauthor | Kim,Young-Chul | - |
| dc.sector.campus | S | - |
| dc.sector.daehak | 대학원 | - |
| dc.sector.department | 의학과 | - |
| dc.description.degree | Doctor | - |
- Appears in Collections:
- GRADUATE SCHOOL[S](대학원) > MEDICINE(의학과) > Theses (Ph.D.)
- Files in This Item:
There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
