The Regulation Of Ilexonin A On Notch Signaling Pathway And Neurogenesis After Cerebral Ischemia

Objective:To investigate the relationship between the effect of Ilexonin A onnotch signaling pathway and proliferation and differentiation of neural stem cells aftercerebral ischemia-reperfusion,and explore the possible mechanism of repair afterbrain injury.Methods： The model of Middle cerebral artery occlusion (MCAO) wasestablished to cerebral ischemia-reperfusion model by placing an intraluminalfilament at the origin of left middle cerebral artery two hours.The rats were assignedrandomly into:control, sham operation, model and IlexoninA groups. Model groupand IA group were reperfused differernt time respectively. Neuronogical deficitswere assessed post MCAO by Longa’s scoring method. TTC staining was applied tovarify experimental animal models and provide positioning mark. The number ofBrdu/Nestin positive cells, Brdu/NeuN positive cells and NICD positive cells in theperienchyma of brain ischemic tissue were observed by Immunohistochemistry,NICD protein expression were detected by western blotting and the expression ofNotch1, Psen1, Hes1were detected by RT-PCR.Results:(1)Recover of neurological fuction: Neurological deficits of model groupand IA group were significant repaired at1thday after ischemia and reperfusion. TheNeurological deficits were repaired progressively with the prolongation of time.Compare with model group, the neurological deficit score of the IA group was muchless. A significant difference of the neurological deficit score at3thday,7thday and14thday (p<0.01, p<0.05).(2) Neurogenesis in the perienchyma of brain ischemictissue:compare with model group the IA group’s Brdu/Nestin positive cells increasedat3thday (p<0.05),and reached its peak at7thday (p<0.05) after ischemia andreperfusion. Brdu/Neun positive cells slightly express at14thday in model group andIA group.(3)Acitvation of the notch signaling pathway and expression of its genes:compare to control and sham groups, model and IA groups NICD positive cells andprotein increased,futhermore IA groups’were more than model groups’at1thday,3thday and7thday（p<0.01, p<0.05）. The expression of notch signaling pathway moleculeNotch1, PS1, HES1rspectively increased in modle group and IA group at differenttime points. Compare with model group, the IA groups’were much higher（p<0.01）.Conclusion:1.IlexoninA can significantly promote recovery of neurological function after ratscerebral ischemia-reperfusion injury.It may be thought enhance nestin positive cellsthat labeled neural stem cells proliferation in the perienchyma of brain ischemictissue.2.IlexoninA promote expression of notch signaling pathway moleculeNotch1, NICD, PS1, HES1after cerebral ischemia-reperfusion injury, indicateIlexoninA promote activation of notch signaling pathway.