Comparison of Vascular Perturbations in an Aβ-Injected Animal Model and in AD Brain.
Comparison of Vascular Perturbations in an Aβ-Injected Animal Model and in AD Brain.
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在注射Aβ的动物模型和AD脑中血管扰动的比较。
DOI：
10.4061/2011/918280
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发表时间：
2011
影响因子：
--
通讯作者：
McLarnon JG
中科院分区：
文献类型：
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作者：
Jantaratnotai N;Ryu JK;Schwab C;McGeer PL;McLarnon JG
淀粉样蛋白-β肽（Aβ 1-42）海马内注射作为阿尔茨海默病（AD）动物模型的有效性，先前已被认为是在炎症反应性和神经元损伤方面。在这项工作中，我们通过比较体内微血管与人类 AD 脑组织中微血管的选定特性，将动物模型的测试扩展到脉管系统。相对于对照PBS（磷酸盐缓冲盐水），注射Aβ1-42增加了齿状回分子层中微血管的平均数量并减少了微血管的平均长度。动物模型显示 Aβ 1-42 而不是 PBS，注射与微血管形态异常相关，其特征为环状、碎片、旋钮状、不均匀和收缩。特别地，与注射PBS相比，Aβ1-42的收缩微血管（定义为直径小于3μm的血管）的数量显着增加。相比之下，与非痴呆 (ND) 大脑相比，人类 AD 大脑的微血管数量增加，平均长度缩短。此外，AD 大脑中的微血管扰动显示出与注射 Aβ 1-42 的大鼠海马中观察到的相似的形态异常模式。收缩的微血管是 AD 大脑的一个显着特征，但在 ND 组织中很少观察到。这些结果提供了第一个证据，证明肽注射动物模型与 AD 大脑中明显的微血管扰动相比，在微血管扰动方面表现出共性。
The validity of amyloid-β peptide (Aβ 1-42) intrahippocampal injection, as an animal model of Alzheimer's disease (AD), has previously been considered in terms of inflammatory reactivity and neuronal damage. In this work, we have extended the testing of the animal model to vasculature by comparison of selected properties of microvessels in vivo with those in human AD brain tissue. The injection of Aβ 1-42, relative to control PBS (phosphate buffered saline), increased the mean number of microvessels and diminished the mean length of microvessels in the molecular layer of dentate gyrus. The animal model showed Aβ 1-42, but not PBS, injection was associated with abnormalities in morphology of microvessels which were characterized as looping, fragmented, knob-like, uneven, and constricted. In particular, numbers of constricted microvessels, defined as vessels with diameters less than 3 μm, were considerably enhanced for Aβ 1-42, compared to PBS, injection. In comparison, human AD brain demonstrated an elevated number of microvessels with a diminished mean length relative to nondemented (ND) brain. Additionally, microvessel perturbations in AD brain showed a similar pattern of morphological abnormalities to those observed in Aβ 1-42-injected rat hippocampus. Constricted microvessels were a prominent feature of AD brain but were rarely observed in ND tissue. These results provide the first evidence that a peptide-injection animal model exhibits a commonality in perturbations of microvessels compared with those evident in AD brain.