Old Global Cerebral Ischemia Reperfusion Injury Mechanism And The Protective Effect Of Metallothionein

Recently, the morbidity of ICVD is growing . To investigate the pathology of ICVD, to find new therapeutic drugs and roles by using the model of cerebral ischemia and reperfusion has become a key technique in the domain of neuroscience.Neurons may die by necrosis or apoptosis after reperfusion following cerebral ischemia, which depends on'the causes of ischemic brain injury, mild injury mainly leads an apoptosis, whereas severe injury mainly leads a necrosis, in the present study, apoptosis is important, in the course of ischemic brain injury, pathologic changes of the regions in the hippocampus are similar to global cerebral ischemia, meanwhile, the selective vulnerability and the resistivity are not obviously same, though the mechanism is not quite clear, studying more will be effective in numerous neurogenerative disorders, but free radical theory is noted recently, the study of radical scavengers and antioxidants do appear to be on the horizon.In the present study, papers reported about ischemic brain injury are more, but however that involved in old animals are rare, whereas, the amount of old people is increasing following the development of society, the diseases of old people are more and more noted, so studying the patterns of neuronal cell death in regions of hippocampus and the inhibition of metallothionein( MT-1) on apoptosis have a significant sense.In this study, we mainly studied old rats by using young rats as control group, with bilateral carotid arteries occlusion model of rats, we investigated the pathologic changes by light and electron microscopy, immunohistochemistry staining(Tunel and Caspase-3 method) after reperfusion following 10 min forebrain ischemia.meanwhile, we analysised the changes of SOD , GSH-Px and MDA in the brain tissue.so we can observe the patterns of pyramidal cell death in the hippocampus, we also observed the neuroprotection of MT-1.Results showed here indicated there are two patterns of cell death: apoptosis and necrosis, in the course of rat transient global ischemia . the changes of apoptosis in pyramidal cells of hippocampus were different, and following the sequence of the selective vulnerability was:CA1 and CA4>CA2>CA3>DG;there are similar morphological changes on the DNA fragmetation in pyramidal cells of hippocampus and Caspase-3 expression in different reperfusion duration, but the time of DNA fragmetatin appeared was earlier than that of Caspase-3 expression; compared with that in young groups, the ischemic brain injury of old groups was severe and the avdent of apotosis was earlier; MT-1 could inhibit the apoptosis of neuronal cell bodies in regions of hippocampus and play an important role in protecting neurons from ischemic brain injury.In this study, apoptotic biochemical and morphological character of pyramidal cells in the hippocampus was studied, we believed the injury caused by free radicals, of course, the mechanism of ischemic brain injury could not be explained by only one factor, it could be the results of several factors, but these results showed that MT-I could inhibit the apoptosis in regions of hippocampus, this could lead to studying deeply and MT-1 may be a drug clinical use in treating or preventing ischemic brain injury which free radical processes are involved.