ABSTRACT
Objective To analyze the neuroimaging changes of tree shrew models of Alzheimer’ s disease.Methods Nineteen healthy adult female tree shrews were randomly divided into control (5 animals) and model group (14 animals). The model of Alzheimer’s disease was induced by intracerebroventricular injection of Aβ1-40 using a stereotaxic devise and proved successfully by visuospatial congnitive task.The in vivo microstructural changes in the brain of tree shrew AD models and control group (0, 1, 2, 3, 4 weeks) were observed on 1.5T MRI (T2WI), and on 7.0T MRI (12 week)(T2WI, DTI). Results Reference memory errors were increased in the model group at 3 or 4 weeks (P<0.05), and so working memory errors (P<0.05) and period of time to perform (P<0.05, P<0.05, P<0.01) from 2 to 4 weeks.Thus the model was proved to be established successfully.T2WI test and DTI test were carried out.Hippocampus atrophy of the model group at 3 and 4 weeks was observed compared with that at 0 or 1 week or 2 weeks on a 1.5T Philips Gyroscan.Compared with the control group, the temporal horn width in the model group was significantly increased (P<0.01) at 12 weeks on a 7.0T Bruker Biospec Scanner.DTI test at 12 weeks showed that ADC of bilateral hippocampus was up-regulated in the model group ( P<0.01 ) .In the color coded orientation view, loss of the corpus callosum fibers was obvious in the model group. Conclusions Intracerebroventricular injection of Aβ1-40 can lead to learing and memory impairment in tree shrews.There are abnomal MRI signal changes in the brain, and the temporal horn width, hypocampal apparent diffusion coefficient ( ADC) value and corpus callosum damage may provide reference value for the diagnosis of Alzheimer’ s disease.
ABSTRACT
Amyloid beta-peptides (Aβ) are known to undergo active transport across the blood-brain barrier, and cerebral amyloid angiopathy has been shown to be a prominent feature in the majority of Alzheimer׳s disease. Quercetin is a natural flavonoid molecule and has been demonstrated to have potent neuroprotective effects, but its protective effect on endothelial cells under Aβ-damaged condition is unclear. In the present study, the protective effects of quercetin on brain microvascular endothelial cells injured by fibrillar Aβ 1-40 (fAβ 1-40) were observed. The results show that fAβ 1-40-induced cytotoxicity in human brain microvascular endothelial cells (hBMECs) can be relieved by quercetin treatment. Quercetin increases cell viability, reduces the release of lactate dehydrogenase, and relieves nuclear condensation. Quercetin also alleviates intracellular reactive oxygen species generation and increases superoxide dismutase activity. Moreover, it strengthens the barrier integrity through the preservation of the transendothelial electrical resistance value, the relief of aggravated permeability, and the increase of characteristic enzyme levels after being exposed to fAβ 1-40. In conclusion, quercetin protects hBMECs from fAβ 1-40-induced toxicity.