大鼠颅脑损伤后神经干细胞原位诱导、增殖分化及notch信号通路调控机制的实验研究

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1、博士学位论文ExperimentalstudyonsitumobilizationofneuralstemcellsanditsregulationbyNotchsignalingpathwayafter···1‘●一traumaticDraininjuryinadultratsPhDCandidate：SuiLi—senSupervisors：ProfessorJiangXiaodanABSTRACTBackgroundWiththedevelopmentofsocialindustrialization，traumat

2、icbraininjury(TBI)isthemostcommonacquiredinjuryintraumaticinjurywithhighmorbidityandmortalityrates．Themolecularmechanismsofrestorationintheadultcentralnervoussystem(CNS)，afterTBI，werenotclearcompletely．Recentstudiesdemonstratedtheneuralfunctiondeficitandneurondeat

3、hareinevitableformostTBIpatients．Activationofendogenousneuralstemcells(NSCs)underTBIinsitu，thatexistinthecentralnervoussystemofadultmammals，andmostofthemwereatrestingstageinvivoinnodal．NSCshavethepotentialofselfrenewalandcanproliferatethendifferentiateintoneuronsa

4、ndastrocytesundersomecondition，NSCsmaybeinvolvedinneuralfunctionrestoration．Recentstudies／nvivoandin’，ivtodemonstratedNSCsexistedintheCNSofadultmammals，andactivationofNSCscouldfurtherproliferatedifferentiateandbecapableofregeneratingfunctionafterTBI．Themolecularme

5、chanismsunderlyingincreasedproliferationdifferentiationandmigrationofendogenousNSCsafterTBI，stillremainunclearandneedtobeelucidatedtoaiddevelopmentofanovelstrategyforenhancingneurogenesisafterABSTRACTTBI．AlthoughstudiesdemonstratedthatactivationofalotofNSCsinthehi

6、ppocampusdentategyrus(DG)andsubventriculaRzone(svz)couldproliferatedifferentiateintoneuronsandglialcellsafterTBI．，therearecontroversialstudiesonNSCsproliferatinganddifferentiatingintheadultCNSafterTBI．Notchsignalingpathwayhasbeenshowntoplayafundamentalroleinregula

7、tingthefateofNSCsproliferatinganddifferentiating，howeveLthecomplexintrinsicmechanismsofNotchsignalingthatcontrolsandcoordinatesNSCsproliferationanddifferentiationarestillInthisstudy,threepartsweredesignedintheexperiment．Partone，wedevelopedthebraininjurymodeldescri

8、bedbyFeeneywithsomemodification，andidentifiedthemodeloncellarlevelattheaspectofnervebehaviorgrade，generalandpathology．Parttwo，weobservedthechangeprocess