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Increased Susceptibility To Ischemic Brain Damage In A Mouse Model Of Alzheimer’s Disease

Posted on:2015-10-19Degree:MasterType:Thesis
Country:ChinaCandidate:X FengFull Text:PDF
GTID:2284330485495234Subject:Developmental Biology
Abstract/Summary:PDF Full Text Request
Alzheimer’s disease (AD) and stroke are two of the main leading causes of death around the world. The increased susceptibility to ischemic brain damage is one of the many interactions between the two diseases. This susceptibility is not only reflected in a higher risk in patients with AD, but also a more serious damage after ischemia in AD brains. There were many researches on the study of AD or ischemia, but the mechanism of the increased susceptibility to ischemia in AD is still not clear. As the growth of life expectancy and the arrival of an aging society in China, it is particularly important to understand this mechanism.In this experiment, early-onset Alzheimer’s APP/PS1 transgenic mice were used. In order to show neuronal injury or reaction of microglia in AD mice, APP/PS1/YFP and APP/PS1/GFP mice were gained by crossing YFP or GFP mice with APP/PS1 mice. Photothrombosis was used to build ischemic mouse model. Compared to wild-type mice, there were many significant differences in AD brains, including senile plaques, which existed in the cerebral cortex and hippocampus, unhealthy neurons, activated microglia and astrocytes around the senile plaques. On the 3rd day after ischemia, AD mice showed severer impaired performance on both rotarod test and forelimb grip strength test and increased brain infarct volume. Abnormal activation of astrocytes was observed around the ischemic core in the process of ischemia. Blood-brain barrier permeability of the mouse was also measured. AD mice showed increased blood-brain barrier leakage. Claudin-5, which is important to maintain the BBB integrity, also showed a significant decrease in the ischemic brain of AD mice.The results revealed that BBB in AD mice was more vulnerable to ischemic stroke, which may be related to the susceptibility to ischemic brain damage. These findings could help to understand the pathological process of AD and ischemia, and the mechanism of the increased susceptibility to ischemic damage in AD.
Keywords/Search Tags:Cerebral ischemia, Alzheimer’s disease, Behavioral function, Glia, Blood-brain barrier
PDF Full Text Request
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