The Research Of PIERS-EGFP/VEGF Plasmid Neuroprotection Effect After Cerebral Ischemia Reperfusion By Injection To Lateral Cerebral Ventricle Of Rats

ObjectiveTo elucidate whether the over expression of vascular endothelial growth factor (VEGF) in the brain has neuroprotection against cerebral ischemic injury and its neuroprotective mechanism.MethodsFocal cerebral ischemia was made by middle cerebral artery occlusion(MCAO) for 2 hours in adult rat.The condition of local ischemic damage,expression of p-AKT and the ultrastructure in neural cells were confirmed respectively by staining with 2% 2.3.5—triphenyltetrazolium chloride,Western-blotting,and electron microscope.Results24 hours after MCAO,Brain infarction area was differentiated by TTC dyeing.The result showed that control group of imitational operation had no infarction areas.The volume of cerebral infarction in plasmid group reduced significantly compared with ischemia group,(all P＜0.01);Compared with normal group and imitational operation group,the expression of p-AKT in the group of ischemia and plasmid was significantly increased.(P＜0. 01);And the expression of p-AKT in plasmid group increased significantly compared with ischemia group,(all P＜0.01)Electron microscope observation:Sham and normal group:Celluar structure was normal,neurone was in order,nuclear membrane was smooth and integrated,nucleole was intermediate,and its boundary was obviously;Ischemic group:24 hours after reperfusion,neurone was disorder,nuclear membrane was shaped like waves,chromatin concentrate to blocks,cytochondriome was edema,nuclear membrane bilayer structure was unclear,cytochondriome crest was fragmented or even disappeared,rough endoplasmic reticulum distend obviously;Plasmid group:24 hours after reperfusion,pericaryon and nucelus swelled,nuclear envelope was clear,chromatin increased a little and gathered on edge.cytochondriome was edema mild or moderate.Nuclear membrane bilayer structure was unclear partly, cytochondriome crest was fragmented partly or still integrity.Rough endoplasmic reticulum was edema mild or moderate.Ultrastructural analysis showed that the neuron damage and edema was significantly abatement in plasmid group compared with ischemia group.ConclusionPlasmid pIERS-EGFP-mediated transfer of VEGF gene plays neuroprotective roles in pathophysiological process following cerebral ischemic injury in adults,and PI3K/AKT pathway may play a role in VEGF's neuroprotective activty.