Visualization of microbleeds with optical histology in mouse model of cerebral amyloid angiopathy.
Visualization of microbleeds with optical histology in mouse model of cerebral amyloid angiopathy.
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DOI：
10.1016/j.mvr.2016.02.002
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发表时间：
2016-05
影响因子：
3.1
通讯作者：
Choi B
中科院分区：
文献类型：
--
作者：
Lo P;Crouzet C;Vasilevko V;Choi B
脑淀粉样血管病（CAA）是一种神经血管疾病，与自发性微出血的数量和大小增加密切相关。常规方法的磁共振成像检测微出血，和正电子发射断层扫描与匹兹堡化合物B成像淀粉样蛋白沉积，可以分别证明存在微出血和CAA在受影响的大脑在体内，但是，仍然是一个关键的需要强有力的证据表明，CAA参与微出血的形成。在这里，我们显示在Tg2576阿尔茨海默氏病小鼠模型，组织化学染色和称为光学组织学的光学透明化方法的组合，使大脑微血管，微出血和淀粉样蛋白沉积的同时，共注册的三维可视化。我们的数据表明，微出血局限于受血管淀粉样蛋白沉积影响的大脑区域。所有观察到的微血管（n = 39）都与CAA影响的血管非常接近（0至144 µm）。我们的数据表明，CAA相关微出血的主要类型与出血性微血管渗漏或破裂有关。拟议的方法和工具的方法将允许未来的CAA和微出血之间的关系在疾病发展和治疗策略的响应研究。
Cerebral amyloid angiopathy (CAA) is a neurovascular disease that is strongly associated with an increase in the number and size of spontaneous microbleeds. Conventional methods of magnetic resonance imaging for detection of microbleeds, and positron emission tomography with Pittsburgh Compound B imaging for amyloid deposits, can separately demonstrate the presence of microbleeds and CAA in affected brains in vivo; however, there still is a critical need for strong evidence that shows involvement of CAA in microbleed formation. Here, we show in a Tg2576 mouse model of Alzheimer's disease, that the combination of histochemical staining and an optical clearing method called optical histology, enables simultaneous, co-registered three-dimensional visualization of cerebral microvasculature, microbleeds, and amyloid deposits. Our data suggest that microbleeds are localized within the brain regions affected by vascular amyloid deposits. All observed microhemorrhages (n = 39) were in close proximity (0 to 144 µm) with vessels affected by CAA. Our data suggest that the predominant type of CAA-related microbleed is associated with leaky or ruptured hemorrhagic microvasculature. The proposed methodological and instrumental approach will allow future study of the relationship between CAA and microbleeds during disease development and in response to treatment strategies.