The Experimental Studies Of Mechanisms Of Regulation Of Mitochondria On Catecholamines Damaging To Neuronal Cell Following Traumatic Brain Injury

The brain tissue damage resulted from both direet meehanical injury andseeondary brain imPairment.They were related and cooPerated in a series ofevents of eells and moleeules.The researeh of brain damage reeentlycmPhasis on evolution of secondary brain imPairment after trau们natie braininjury(TBI).Inereasing evidenees showed that TBI might induee eell death.However, under eircumstanee of normal Physiologieal and in manyPathologieal Proeesses,eell death emerged tyPieal eharaeteristies of apoPtosis.TBI indueing apoPtosis of a large number of neurons had been肋own.Therefore further studies on the meehhasms of neuron apoPtosis might giVea new insighton the treatnlent ofTBI. A series of studies Provided convineing evidence that PathologiealProeesses of secondary brain ilnPairment involved in a eascade ofbioehemieal ehanges of TBI.Serve as endogenous neurotransmitter in thenervous system,the ehanges Catecholamines(CAs)reflected a sensitivemarker of metabolism.CAs,sueh as DA,NE andE,Played an imPortant rolein normal neuroPhysiobiologieal Proeesses of eentral nervous system,as wellas involved in Pathologieal Proeesses of seeondary brain imPairment.Reeentstudies de们以onstrated that CAs was disturbed following seeondal,yilllPairment of neurodegenerative disorders and TBI.Our in vitro indicatedthat overdose CAs were toxieally to neurons and might induee aPoPtosis ofthem direetly,几吐hermore,there time eourse and dose一response·However,whether this sitL讯tione劝sted in vivo remained unelear. Reeent studies rePresented that mitoeholidria(Mt) eatried out manyimPortant fullction exeePt ATP synthesis:generating reaetive oxygen sPeeies(ROS),regulating oxidoreduction Potential alld eellular oxidoreduction signaltransduetion,as well as the apoPtosis of neurons and the exPression of genes.In addition,Mt also Played an lmPortant role in living thing,5 grov改h,develoPment,aging,disease and death.Reeent bioehemieal studies revealedanother asPeet of Mt funetion:indueing aPoPtosis and eell death by triggeringsPecifie bioehemical reaetion.The Previous researches on TBI indueingneuron apoPtosis focused on stUdying the morphologieal and signallingPathways ehanges of nueleus.There were relatiVely few rePorts on MtPlaying role in neuronal eell apoPtosis after TBI, Therefore,these studles iultially established damage model,andinvestigated the meehanisms and the exPanding role of Mt on CAs inducingneuronal eell apoPtosis after TBI.Part 1 Studies on the ehanges of CAs and its effeet involved in neuronaleells after TBIPurPose:To identify the eharaeteristies of the ehanges of CAs and its effeetsinvolved in neu『onal eellsMethods: 1 .Healthy male SPrague一Dawley(SD)rats were randomized into thesham一injury grouP andl,6,24,48, 72,168h grouP after traumatie injured.The eontUsion model on brain was made use ffee一falling body. 2 .The dead form of neuronal eells in injured eortex and hiPPocamPuswere deteeted using Tunel and Hoehest 33342 fluoreseenee staining. 3 .The exPression of TH in injured eortex,hiPPoeamPus and brain stemwere detected and semiquatitative measurelnents by fluoreseeneehistochemistry technique. 4 .The eontain of ROS of neuronal eells in living brain sliees werelabeled withZ'7'一diehlorodi勿drofluroresein diaeetate and semiquatitativemeasllre幻 nellts.l0 5 .ROS affecting neuronal eells were obs柳ed living brain slieesdouble一labeled withZ'7'一diehlorodihydrofluroresein diacetate andProgPidium iodide.Results: 1)APoPtotie eell emerged in injured eortex and hiPPoeamPus at lh,thenincreased gradually,reaehed the Peak at 24h.There,vere a few neuronal eellswith weak and dll'f1卫se brown TIJNEL Positive staining in sham一injury grouP. 2)At early Period(lh) after TBI,the Positive exPression of TH ininjured eortex and hiPPoeamPus signifieantly increased eomPared with thesham一injury grouP,and reaeh the Peak at 6h,then began to deereased,apParently deerea...