Transient focal cerebral ischemia/reperfusion induces early and chronic axonal changes in rats: its importance for the risk of Alzheimer's disease.
Transient focal cerebral ischemia/reperfusion induces early and chronic axonal changes in rats: its importance for the risk of Alzheimer's disease.
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DOI：
10.1371/journal.pone.0033722
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Dai J
中科院分区：
文献类型：
--
作者：
Zhang Q;Gao T;Luo Y;Chen X;Gao G;Gao X;Zhou Y;Dai J
已知阿尔茨海默型痴呆和脑缺血随着年龄的增长以相当的速度增加。近年来的研究表明脑缺血可能是阿尔茨海默病（AD）的发病机制之一，但两者之间的神经病理学关系尚不清楚。研究表明，以轴突运输障碍、轴突肿胀和静脉曲张为主要表现的轴突病变是AD的一个显著特征，并可能在AD的神经病理机制中发挥重要作用。本研究采用大鼠短暂性局灶性脑缺血/再灌注（Middle cerebral artery occlusion，MCAO）模型，采用在体示踪技术和分级分析方法，观察了不同脑区（皮层、海马和纹状体）神经元轴突的早期和慢性变化。同时，结合免疫组化和蛋白质印迹技术，分析了AD神经病理过程中β-淀粉样蛋白42（Aβ42）和过度磷酸化Tau蛋白的表达与轴突变化的关系。随后，我们发现短暂脑缺血/再灌注后6小时甚至4周，产生明显的轴突肿胀和静脉曲张。在缺血脑区未观察到Aβ斑块或Aβ42过表达，但在缺血皮质可检测到位点特异性过度磷酸化Tau。提示短暂性脑缺血/再灌注可引起早期和慢性轴突改变，这可能是影响临床预后的重要机制，并可能促进卒中后AD的发展。
The dementia of Alzheimer's type and brain ischemia are known to increase at comparable rates with age. Recent advances suggest that cerebral ischemia may contribute to the pathogenesis of Alzheimer's disease (AD), however, the neuropathological relationship between these two disorders is largely unclear. It has been demonstrated that axonopathy, mainly manifesting as impairment of axonal transport and swelling of the axon and varicosity, is a prominent feature in AD and may play an important role in the neuropathological mechanisms in AD. In this study, we investigated the early and chronic changes of the axons of neurons in the different brain areas (cortex, hippocampus and striatum) using in vivo tracing technique and grading analysis method in a rat model of transient focal cerebral ischemia/reperfusion (middle cerebral artery occlusion, MCAO). In addition, the relationship between the changes of axons and the expression of β-amyloid 42 (Aβ42) and hyperphosphorylated Tau, which have been considered as the key neuropathological processes of AD, was analyzed by combining tracing technique with immunohistochemistry or western blotting. Subsequently, we found that transient cerebral ischemia/reperfusion produced obvious swelling of the axons and varicosities, from 6 hours after transient cerebral ischemia/reperfusion even up to 4 weeks. We could not observe Aβ plaques or overexpression of Aβ42 in the ischemic brain areas, however, the site-specific hyperphosphorylated Tau could be detected in the ischemic cortex. These results suggest that transient cerebral ischemia/reperfusion induce early and chronic axonal changes, which may be an important mechanism affecting the clinical outcome and possibly contributing to the development of AD after stroke.
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影响因子：
5.7
作者：
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通讯作者：
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