Neuronal loss without amyloid-β deposits in the thalamus and hippocampus in the late period after middle cerebral artery occlusion in cynomolgus monkeys
Neuronal loss without amyloid-β deposits in the thalamus and hippocampus in the late period after middle cerebral artery occlusion in cynomolgus monkeys
复制标题
食蟹猴大脑中动脉闭塞后期丘脑和海马中无淀粉样蛋白沉积的神经元损失
DOI：
10.1111/bpa.12764
复制
发表时间：
2019-07-21
期刊：
影响因子：
6.4
通讯作者：
Zeng, Jinsheng
中科院分区：
文献类型：
--
作者：
Ouyang, Fubing;Chen, Xinran;Zeng, Jinsheng
关于局灶性脑梗死是否有助于脑淀粉样蛋白β（A β）沉积，如在阿尔茨海默病中观察到的，存在明确的证据。在这项研究中，我们的目的是评估存在的A β沉积在同侧丘脑和海马中风后12个月的非人类灵长类动物，其大脑结构和功能与人类相似。4只幼年雄性食蟹猴单侧永久性大脑中动脉闭塞（MCAO），另4只假手术猴作为对照。所有猴子在术后第7天接受磁共振成像检查，以评估梗死的位置和大小。在手术后12个月处死时，用免疫组织化学方法检测远离梗死灶的同侧未受影响的丘脑和海马中神经元、星形胶质细胞、小胶质细胞的数量和A β负荷。硫磺素S和刚果红染色用于鉴定淀粉样蛋白沉积。使用识别A β肽的N-末端和C-末端表位的多种A β抗体以避免抗体交叉反应性。采用酶联免疫吸附试验检测脑脊液（CSF）和血浆中A β水平。最初的梗死局限于左侧颞叶、顶叶、岛叶皮质和皮质下白色物质，而丘脑和海马保持完整。值得注意的是，与对照组相比，中风后12个月MCAO组同侧丘脑和海马中的神经元数量较少，胶质细胞较多（均P < 0.05）。然而，在丘脑或海马中没有细胞外A β斑块的迹象。两组脑脊液和血浆中A β（40）、A β（42）水平及A β（40）/A β（42）比值差异均无统计学意义（P > 0.05）。这些结果表明，显着的继发性神经元丢失和反应性胶质细胞增生发生在非人灵长类动物的MCAO后的后期，在无A β沉积的未受影响的丘脑和海马。
Conflicting evidence exists regarding whether focal cerebral infarction contributes to cerebral amyloid-beta (A beta) deposition, as observed in Alzheimer's disease. In this study, we aimed to evaluate the presence of A beta deposits in the ipsilateral thalamus and hippocampus 12 months post-stroke in non-human primates, whose brains are structurally and functionally similar to that of humans. Four young male cynomolgus monkeys were subjected to unilateral permanent middle cerebral artery occlusion (MCAO), and another four sham-operated monkeys served as controls. All monkeys underwent magnetic resonance imaging examination on post-operative day 7 to assess the location and size of the infarction. The numbers of neurons, astrocytes, microglia and the A beta load in the non-affected thalamus and hippocampus ipsilaterally remote from infarct foci were examined immunohistochemically at sacrifice 12 months after operation. Thioflavin S and Congo Red stainings were used to identify amyloid deposits. Multiple A beta antibodies recognizing both the N-terminal and C-terminal epitopes of A beta peptides were used to avoid antibody cross-reactivity. A beta levels in cerebrospinal fluid (CSF) and plasma were examined using enzyme-linked immunosorbent assay. The initial infarct was restricted to the left temporal, parietal, insular cortex and the subcortical white matter, while the thalamus and hippocampus remained intact. Of note, there were fewer neurons and more glia in the ipsilateral thalamus and hippocampus in the MCAO group at 12 months post-stroke compared to the control group (all P < 0.05). However, there was no sign of extracellular A beta plaques in the thalamus or hippocampus. No statistically significant difference was found in CSF or plasma levels of A beta(40), A beta(42) or the A beta(40)/A beta(42) ratio between the two groups (P > 0.05). These results suggest that significant secondary neuronal loss and reactive gliosis occur in the non-affected thalamus and hippocampus without A beta deposits in the late period after MCAO in non-human primates.