炎症与缺血共同作用导致成年大鼠脑内髓鞘损伤以及髓鞘、淀粉样β蛋白和淀粉样前体蛋白的斑块样聚集。
Inflammation Combined with Ischemia Produces Myelin Injury and Plaque-Like Aggregates of Myelin, Amyloid-β and AβPP in Adult Rat Brain.
作者信息
Zhan Xinhua, Cox Christopher, Ander Bradley P, Liu Dazhi, Stamova Boryana, Jin Lee-Way, Jickling Glen C, Sharp Frank R
机构信息
Department of Neurology, MIND Institute, University of California at Davis, Sacramento, CA, USA.
Alzheimer's Disease Center, University of California at Davis, Sacramento, CA, USA.
出版信息
J Alzheimers Dis. 2015;46(2):507-23. doi: 10.3233/JAD-143072.
BACKGROUND
Ischemia, white matter injury, and Alzheimer's disease (AD) pathologies often co-exist in aging brain. How one condition predisposes to, interacts with, or perhaps causes the others remains unclear.
OBJECTIVES
To better understand the link between ischemia, white matter injury, and AD, adult rats were administered lipopolysaccharide (LPS) to serve as an inflammatory stimulus, and 24 h later subjected to 20-min focal cerebral ischemia (IS) followed by 30-min hypoxia (H).
METHODS
Myelin and axonal damage, as well as amyloid-β (Aβ) and amyloid-β protein precursor (AβPP) deposition were examined by Western blot and immunocytochemistry following LPS/IS/H. Findings were compared to the 5XFAD mouse AD brain.
RESULTS
Myelin/axonal injury was observed bilaterally in cortex following LPS/IS/H, along with an increase in IL-1, granzyme B, and LPS. AβPP deposition was present in ischemic striatum in regions of myelin loss. Aβ(1-42) and AβPP were deposited in small foci in ischemic cortex that co-localized with myelin aggregates. In the 5XFAD mouse AD model, cortical amyloid plaques also co-localized with myelin aggregates.
CONCLUSIONS
LPS/IS/H produce myelin injury and plaque-like aggregates of myelin. AβPP and Aβ co-localize with these myelin aggregates.
背景
缺血、白质损伤和阿尔茨海默病（AD）病理改变在衰老大脑中常同时存在。一种情况如何诱发、与其他情况相互作用或可能导致其他情况仍不清楚。
目的
为了更好地理解缺血、白质损伤和AD之间的联系，给成年大鼠注射脂多糖（LPS）作为炎症刺激，24小时后进行20分钟的局灶性脑缺血（IS），随后进行30分钟的缺氧（H）。
方法
在LPS/IS/H后，通过蛋白质免疫印迹法和免疫细胞化学法检测髓鞘和轴突损伤，以及淀粉样β蛋白（Aβ）和淀粉样β蛋白前体（AβPP）的沉积。将结果与5XFAD小鼠AD脑进行比较。
结果
在LPS/IS/H后，双侧皮质观察到髓鞘/轴突损伤，同时白细胞介素-1、颗粒酶B和LPS增加。在髓鞘丢失区域的缺血纹状体中存在AβPP沉积。Aβ（1-42）和AβPP沉积在缺血皮质的小病灶中，与髓鞘聚集体共定位。在5XFAD小鼠AD模型中，皮质淀粉样斑块也与髓鞘聚集体共定位。
结论
LPS/IS/H导致髓鞘损伤和髓鞘样聚集体形成。AβPP和Aβ与这些髓鞘聚集体共定位。
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