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Objective To develop specific targeted magnetic biomarkers which can selectively mark the senile plaques in Alzheimer' s disease (AD) and verify its feasibility and validity.Methods Aβ1-40 peptide and Tat-PTD ( Tat-protein transduction domain) was binded with dextran-coated ultrasmall superparamagnetic iron oxide ( USPIO) particles.Visualization of plaques in vivo in Alzheimer transgenic mice was investigated at 7.0 Tesla using T2 sequences after intravenous administration of the targeted nanoiron contrast agent and verified by histological staining.Results The targeted nano-iron contrast agent could enter the cultured neural stem cells,and was able to accelerate T2 relaxation rates of water protons in the cells and negatively reinforce the T2 signal intensity in the labeled cells.Plaques were specifically detected in vivo by magnetic resonance imaging ( MRI) and correlated well with histological staining after injection of nano-iron contrast agent into the APP/PS1 mice.Conclusion The targeted nano-iron contrast agent has the ability of selectively labeling the senile plaques in AD brain tissues in vivo,which might enable the early detection of plaques by MRI and can be further applied in the studies of early diagnosis of AD.
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Objective To observe senile plaque and iron deposition in cortex and hippocampus of the Alzheimer's disease ( AD ) transgenic mice and investigate their influence on T2 relaxation time.Method All AD transgeic mice were divided into three groups: young group(2,4 months), adult group (6,8,10 months), old group (12,14,16 months), and C57BL/6J mice were as control and were scanned in order by using 4.7 T MR system.Regions of interest (ROI) corresponding to cortex, hippocampus,thalamus, striatum were manually drawn on MR images and T2 MR relaxation times of each ROI were calculated.After MR scan, these mice were decapitated and stained for iron and senile palques.The number of plaque and iron, plaque burden, iron load in cortex and hippocampus were acquired using image pro plus software.Result T2 relaxation times of each group were as following: wild type ( cortex (49.5 ± 2.1 ) ms,hippocampus (51.6 ± 1.1 ) ms ); young ( cortex ( 49.7 ± 0.5 ) ms, hippocampus ( 50.7 ± 0.7 ) ms ); adult (cortex(47.2 ±0.8) ms, hippocampus(47.7 ±0.9) ms) and old (cortex(44.6 ±0.8) ms, hippocampus (45.3 ±0.4)ms).T2 relaxation times in cortex and hippocampus of each group had statistical differences ( cortex F = 18.620, P ＜ 0.01; hippocampus F = 67.925, P ＜ 0.01 ); Compared with young group and wild type mice, T2 relaxation times in corex and hippocampus of adult group mice were decreased significantly.At the same time, T2 relaxation times in old group mice were reduced compared with adult group ( Adult vs young: cortex q =4.284, P ＜0.01, hippocampus q =7.902, P ＜0.01; adult vs wild type: cortex q =4.424, P＜0.05, hippocampus q = 11.450, P ＜0.01; old w adult: cortex q =4.812, P ＜0.01,hippocampus q = 7.034, P ＜ 0.01 ).Histochemical staining for senile plaques found that senile plaques was deposited as early as 4 month.Iron deposition in hippocampus and cortex were detected by perl-DAB as early as 6 months of age, and there was an overall increase in number and load of plaques and iron with age.A positive correlation was observed between plaque burden and iron load ( r = 0.931, P ＜ 0.01 ).At the same time, plaque burden and iron load were negatively correlated with T2 relaxation times ( plaque burden and T2 relaxation times r = - 0.884, P ＜ 0.01; iron load and T2 relaxation times r = - 0.827, P ＜ 0.01 ).Conclusion The changes of T2 relaxation time in AD transgenic mice are attributed to iron and senile plaques.MR T2 relaxation time is a sensitive marker to diagnosis for AD and screen antidementia drugs.
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Objective To study the effects of urinary kallidinogenase (kallikrein) on focal cerebral blood flow (CBF) following cerebral infarction in rats by laser speckle imaging.Methods Permanent middle cerebral artery occlusion (MCAO) was induced in male Sprague-Dawley rats by the intraluminal filament technique.Laser speckle imaging was used to measure CBF in the ischemic cortical area and middle cerebral artery territory.The brain was stained with 2,3,5-triphenyltetrazolium chloride (TTC) to determine the infarct size.Neurological deficit score was measured.Results CBF increased in both hemispheric cortical area and MCA territory on the first and second days following urinary kallikrein administration at high dose but not at low dose.Larger blood vessel diameter and increased blood flow velocity were noticed in the high dose group in some arteries when compared to the low dose group and normal saline control group.At 36 h after cerebral ischemia,the brain infarct size was 10.14% ±3.02% ,25.99% ±3.90% and 27.10% ±3.32% in high, low dose and normal saline control groups,respectively.The infarct size was significantly smaller in the high ( F = 61.14, P<0.01 ) but not low dose group when compared to the normal saline control group.The neurological deficit was milder in the high dose group but not the other two groups at 4 h after cerebral ischemia; however, there were no differences among the groups at 36 h after MCAO.Conclusions Urinary kallidinogenase can reduce cerebral infarction volume and neurological deficit in rats following focal cerebral ischemia.These effects may be attributed to enhanced collateral circulation and improved CBF in the hemispheric cortical area and MCA territory.
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The effects of vascular endothelial growth factor (VEGF) on neural differentiation of human embryonic stem cells (hESCs) in vitro and the possible mechanism were observed. The hESCs lines, TJMU1 and TJMU2, were established and stored by our laboratory. hESCs differentiated into neuronal cells through embryonic body formation. In this induction process, hESCs were divided into three groups: group A, routine induction; group B, routine induction+10 ng/mL VEGF; group C, routine induction+10 ng/mL VEGF+10 ng/mL VEGFR2/Fc. OCT4, Nestin and GFAP in each group were detected by RT-PCR, and the cells expressing Nestin and GFAP were counted by immunofluorescence. The percentage of Nestin positive cells in group B was significantly higher than in groups A and C, while the percentage of GFAP positive cells in group B was significantly lower than in groups A and C (P0.05). It was concluded that VEGF, via VEGFR2, stimulated the neural differentiation of hESCs in vitro.
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The article introduces the pathogenesis of genetic and acquired thrombophilia and elucidates the relationships among thrombophilia, pediatric stroke, adult ischemic stroke and cerebral venous thrombosis. Meanwhile, it briefly introduces the relationships between acquired thrombophilia and cerebrovascular diseases.