Arterial Pulsations cannot Drive Intramural Periarterial Drainage: Significance for Aβ Drainage
Arterial Pulsations cannot Drive Intramural Periarterial Drainage: Significance for Aβ Drainage
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DOI：
10.3389/fnins.2017.00475
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发表时间：
2017-08-24
影响因子：
4.3
通讯作者：
Richardson, Giles
中科院分区：
文献类型：
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作者：
Diem, Alexandra K.;Sharp, Matthew MacGregor;Richardson, Giles
阿尔茨海默病（AD）是最常见的痴呆症，迄今为止没有治愈或有效的预防方法。认知能力下降与毛细血管和动脉壁中淀粉样蛋白（A β）的积累有关。我们的研究小组已经证明，间质液和A - β是沿着毛细血管和动脉的基底膜，即壁内动脉周围引流（IPAD）途径从大脑中清除的。随着年龄的增长和动脉硬化，动脉壁的硬化，这一途径的功能失效，A β在动脉壁中积累。在这项研究中，我们测试了动脉搏动驱动IPAD的假设，以及瓣膜机制确保净引流方向与血流方向相反。利用排水机制的数学模型验证了这一假设。我们首先证明，动脉搏动的强度不足以产生与实验观察相媲美的排水速度。其次，我们证明了一个阀门机制，如IPAD路径的定向渗透率是实现净逆流所必需的。通过使用脉冲调制器评估小鼠IPAD的模式，证实了数学模拟结果，显示IPAD没有明显改变。我们的研究结果表明，除心脏搏动外的其他力量是有效IPAD的原因。
Alzheimer's Disease (AD) is the most common form of dementia and to date there is no cure or efficient prophylaxis. The cognitive decline correlates with the accumulation of amyloid-beta) (A beta) in the walls of capillaries and arteries. Our group has demonstrated that interstitial fluid and A beta are eliminated from the brain along the basement membranes of capillaries and arteries, the intramural periarterial drainage (IPAD) pathway. With advancing age and arteriosclerosis, the stiffness of arterial walls, this pathway fails in its function and A beta, accumulates in the walls of arteries. In this study we tested the hypothesis that arterial pulsations drive IPAD and that a valve mechanism ensures the net drainage in a direction opposite to that of the blood flow. This hypothesis was tested using a mathematical model of the drainage mechanism. We demonstrate firstly that arterial pulsations are not strong enough to produce drainage velocities comparable to experimental observations. Secondly, we demonstrate that a valve mechanism such as directional permeability of the IPAD pathway is necessary to achieve a net reverse flow. The mathematical simulation results are confirmed by assessing the pattern of IPAD in mice using pulse modulators, showing no significant alteration of IPAD. Our results indicate that forces other than the cardiac pulsations are responsible for efficient IPAD.