Background

Lead (Pb) is an environmental factor has been suspected of contributing to the dementia including Alzheimer’s disease (AD). Our previous studies have shown that Pb exposure at the subtoxic dose increased brain levels of beta-amyloid (Aβ) and amyloid plaques, a pathological hallmark for AD, in amyloid precursor protein (APP) transgenic mice, and is hypothesized to inhibit Aβ clearance in the blood- cerebrospinal fluid (CSF) barrier. However, it remains unclear how different levels of Pb affect Aβ clearance in the whole blood-brain barrier system. This study was designed to investigate whether chronic exposure of Pb affected the permeability of the blood-brain barrier system by using the Dynamic Contrast-Enhanced Computerized Tomography (DCE-CT) method.

Methods

DEC-CT was used to investigate whether chronic exposure of toxic Pb affected the permeability of the real-time blood brain barrier system.

Results

Data showed that Pb exposure increased permeability surface area product, and also significantly induced brain perfusion. However, Pb exposure did not alter extracellular volumes or fractional blood volumes of mouse brain.

Conclusion

Our data suggest that Pb exposure at subtoxic and toxic levels directly targets the brain vasculature and damages the blood brain barrier system.

中文翻译：

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DCE-CT对血脑屏障系统慢性铅影响的评价

背景

铅 (Pb) 是一种环境因素，被怀疑会导致痴呆症，包括阿尔茨海默病 (AD)。我们之前的研究表明，亚毒性剂量的铅暴露增加了淀粉样前体蛋白 (APP) 转基因小鼠中 β-淀粉样蛋白 (Aβ) 和淀粉样蛋白斑块的脑水平，这是 AD 的病理标志，并被假设为抑制 Aβ 清除血脑脊液 (CSF) 屏障。然而，尚不清楚不同水平的 Pb 如何影响全血脑屏障系统中的 Aβ 清除。本研究旨在通过使用动态对比增强计算机断层扫描 (DCE-CT) 方法研究长期接触铅是否影响血脑屏障系统的通透性。

方法

DEC-CT 用于研究有毒铅的慢性暴露是否影响实时血脑屏障系统的通透性。

结果

数据表明，铅暴露增加了渗透性表面积乘积，并且还显着诱导了脑灌注。然而，铅暴露并没有改变小鼠大脑的细胞外体积或血容量分数。

结论

我们的数据表明，亚毒性和毒性水平的铅暴露直接针对脑血管系统并损害血脑屏障系统。