| Chapter ⅠMechanism of nerve regeneration in dentate gyrus of hippocampus after ischemic stroke in young gerbils.Objective:To observe the differences of neural function recovery,DG cell proliferation,neuroblast differentiation and nerve regeneration between young and old gerbils after ischemic stroke,and to explore the regulatory mechanism of nerve regeneration after ischemic stroke in young gerbils,so as to provide therapeutic targets for ischemic stroke in young gerbils.Methods:The model of transient global cerebral ischemia was established in gerbils.Morris water maze and neurological function score were used to detect the recovery of neurological function in gerbils;immunohistochemical staining was used to observe the neuronal damage in hippocampal CA1 area,cell proliferation and differentiation of neuroblasts in DG area after ischemia;immunofluorescence NeuN/BrdU co-localization was used to detect nerve regeneration,and Western blot was used to detect the expression of ERK signaling pathway and autophagy related proteins.ERK inhibitor(U0126)and autophagy inhibitor(3MA)were used to observe the cell proliferation,neuroblastoid differentiation and nerve regeneration in DG area after global cerebral ischemia.Results:1.Water maze and neurological function score showed that the cognitive and motor function rehabilitation ability of young gerbils was better than that of old gerbils after ischemic stroke.2.The results of immunohistochemistry showed that the number of cell proliferation,neuroblastoid differentiation and nerve regeneration in DG area of young gerbils were significantly higher than that of old gerbils at 28 days after ischemic stroke.3.Western blot results showed that the expression of ERK signaling pathway and autophagy related protein in hippocampus of young gerbils was higher than that of old gerbils after ischemic stroke.4.After ERK or autophagy inhibition and treatment,the recovery ability of cognitive and motor function of young gerbils decreased.Conclusion:After transient global cerebral ischemia,young gerbils can promote cell proliferation,neuroblastoid differentiation and nerve regeneration by regulating the expression of ERK signaling pathway and autophagy related protein level,and ultimately improve the cognitive impairment and promote the recovery of nerve function.Chapter ⅡProtective effect and molecular mechanism of Taxifolin on ischemic strokeObjective:To study the protective effect of Taxifolin(Tax)on cerebral ischemia-reperfusion injury and its molecular mechanism.Methods:The gerbils and ICR mice were randomly divided into sham group,isch group,20 mg/kg Tax+ isch group and 40 mg/kg Tax+isch group.According to the grouping requirements,gerbils were selected to establish transient global cerebral ischemia model by bilateral common carotid artery occlusion,ICR mice were selected to establish focal cerebral ischemia-reperfusion model by middle cerebral artery embolization.The morphology and number of hippocampal CA1 cells in gerbils were evaluated by CV staining.Immunohistochemical staining was used to observe the changes of neuron,astrocyte,microglia,platelet endothelial cell adhesion molecule-1,connexin-1,tight junction protein-5 and diacortisone in mice and gerbils.ERK and Nrf2 signaling pathway related proteins were detected by Western blot.Results:1.Tax intervention significantly improved neurological rehabilitation,reduced neuronal death in hippocampal CA1 area,promoted neural differentiation in DG area,inhibited the activation of glial cells,enhanced the immune expression of ZO-1 and PECAM-1,and increased the protein expression of ERK signaling pathway in hippocampal area after ischemic stroke.2.Tax treatment group significantly reduced the symptoms of neurological injury,the volume of cerebral infarction and the death of neurons in hippocampal CA1 area and cortex of ICR mice after focal cerebral ischemic stroke;at the same time,it inhibited the activation of astrocytes and microglia;and Tax treatment significantly increased the protein expression of Nrf2 and HO-1 in penumbra,alleviated the apoptosis induced by ischemia-reperfusion injury.Conclusion:1.Tax can significantly improve the neuronal death and neurological deficit caused by whole brain and focal stroke;2.Tax can significantly reduce the activation of glial cells after whole brain and focal stroke;3 Tax can significantly improve the blood-brain barrier damage caused by whole brain stroke and activate the expression of key proteins of ERK signaling pathway,which is closely related to its protective effect;4.Tax plays a neuroprotective role by activating Nrf2 signaling pathway after focal stroke. |
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