The Role Of Oligodendrocyte Precursor Cells In Epileptogenesis

PARTⅠTHE DYNAMIC CHANGES OF MYELIN ANDOLIGODENDROCYTE AT DIFFERENT TIME POINTS OFEPILEPTOGENESISObjective:To explore the dynamic changes of myelin and matureoligodendrocytes in hippocampus at different stages of epileptogenesis.Methods:One hundred and six adult rats (sixteen in the controlgroup,ninety in the experimental group)were evaluated.The rats in theexperimental groups were induced status convulsion by lithium-pilocarpineintraperitoneally, then were monitored by video and wireless EEGtelemetry.The expression of myelin basic protein(MBP) were detected byimmunofluorescence and western blot;The morphological changes ofmature oligodendrocytes were detected by immunofluorescence staining ofCC1,while the expression of CNPase were detected by western blot.Results:The results showed that EEG changes in different time pointsafter SC were consistent with different stages of epileptogenesis;Comparedwith the control group,the expression of MBP, CNPase protein weredecreased in the acute phase after SC,and continued to decrease thoughoutthe whole process of epileptogenesis. CC1positive cells in the hippocamp-us were decreased at different time points of epileptogenesis.Conclusion:Myelin and oligodendrocytes in the hippocampus were ongoing damaged throughout the whole process of epileptogenesis. PARTⅡTHE ROLE OF OLIGODENDROCYTEPRECURSOR CELLS IN EPILEPTOGENESISObjective:To explore the dynamic changes of oligodendrocyteprecursor cells and its relevant regulatory factors during epileptogenesis.Methods:The adult rats in the experimental group were induced statusconvulsion by lithium-pilocarpine intraperitoneally, then were monitoredby video and wireless EEG telemetry.The number and morphologicalchanges of oligodendrocyte precursor cells were detected byimmunofluorescence of NG2,while the expression of PDGFR-α,olig1,olig2at different stages of epileptogenesis were detected by western blot.Results:Oligodendrocyte precursor cells in the hippocampus of theexperimental group were actived in the acute stage of epileptogenesis,thenumber of which was significantly higher than that in the nomal controlgroup in acute stage,latenty stage as well as chronic phase.The number ofOPC began to decrease at chronic stage and finally were lower than that inthe nomal control group in late chronic stage.The expression oftranscription factor olig1and olig2in hippocampus of the experimentalgroups began to increase at the acute stage of epileptogenesis, then reacheda peak at the latency stage following by a sharp decline at the chronicstage.During the chronic stage as well as the late chronic stage the amountof olig1and olig2protein was lower than that in the normal control group.Conclusion: The increase in the number and active form inmorphology of oligodendrocyte precursor cells during the eary stages of epileptogenesis may be the endogenous repair mechanisms induced bydemyelination. Transcription factors regulating the differentiation ofoligodendrocyte precursor cells increased during the acute and latencystage of epileptogenesis may promote OPC differentiation, assist OPC toparticipate in the endogenous myelin repair. The sharp decline in thechronic stage may be one of the causes of ongoing myelin damage duringepileptogenesis. PART Ⅲ THE EFFECT OF DEXAMETHASONE IN THEPROCESS OF EPILEPTOGENESISObjective:To explore whether dexamethasone can influenceepileptogenesis through repairing myelin damage after status convulsion.Methods: Sixty-eight adult rats were randomly assigned into thenomal control group,the DEX control group and the experimentalgroup.The experimental group were induced status convulsion bylithium-pilocarpine intraperitoneally. The surviving rats were randomlyassigned into DEX intervention group and the experimental group. Ninetyminutes after SC,the DEX intervention group were intraperitonealadministrated dexamethasone0.5mg/Kg.d for four days,while the DEXcontrol group were given the same amount of dexamethasone. Video andwireless EEG telemetry were used to monitor the spontaneous recurrentseizures during the chronic stage. The expression of MBP,PDGFR-α andCNPase in the hippocampus at chronic stage of epileptogenesis weredetected by western blot. Results: Compared with the control group,dexamethasone can extendthe latency of epileptogenesis,reduce the frequency of SRS during thechronic stage. In addition, dexamethasone can increase the expression ofMBP, reduce the expression of PDGFR-α,and improve the content ofCNPase in the hippocampus of rats at chronic stage of epileptogenesis.Dexamethasone had no effect on myelin, mature oligodendrocytes andOPC of nomal rats.Conclusion: The antiepileptic effect of dexamethasone on lithium-pilocarpine induced epilepsy may occur by promoting OPC differentiat-ing into mature oligodendrocytes to repair the damaged myelin duringepileptogenesis.