Glimcher Shelley A, Holman David W, Lubow Martin, Grzybowski Deborah M
Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio 43210, USA.
Invest Ophthalmol Vis Sci. 2008 Nov;49(11):4721-8. doi: 10.1167/iovs.08-2238. Epub 2008 Jul 9.
The brain's arachnoid membrane with granulations is an important biological barrier whose responsibilities include the transmission of cerebrospinal fluid (CSF) and the regulation of pressure. Membrane disturbance may cause changes that are difficult to replicate with animal models, suggesting the need for a model using human arachnoid membrane with granulations for the study of conditions such as Alzheimer disease, hydrocephalus, and pseudotumor cerebri. The authors detail the development and validation of an ex vivo model of CSF outflow across human arachnoid granulations (AGs) as an approximation of in vivo conditions.
Human AGs were perfused at normal physiological pressure in physiological and nonphysiological directions for permeability data. Fluorescent particle perfusion with electron microscopy identified outflow pathways through the AGs.
This human ex vivo model demonstrated in vivo properties of unidirectionality, particle transport, and ultrastructure, similar to our 2005 in vitro model. The average baseline hydraulic conductivity in the physiological direction (n = 20) was 1.05 +/- 0.15 microL/min/mm Hg/cm(2) compared with 0.11 +/- 0.03 microL/min/mm Hg/cm(2) in the nonphysiological direction (n = 3) under statistically equivalent (P = 0.46) average normal physiological pressures (5.88 +/- 0.22 mm Hg and 6.14 +/- 0.23 mm Hg, respectively).
The ex vivo model is feasible and herein demonstrated. These findings agree with in vivo CSF outflow. This model increases understanding of the clearance not only of CSF but also of metabolites through the arachnoid membrane. Additional evidence suggests, but does not yet prove, that CSF outflow may occur in a similar manner in the arachnoid membrane adjacent to the granulations, in addition to the flow through the AGs. This is a topic for further investigation.
带有颗粒的脑蛛网膜是一种重要的生物屏障，其职责包括脑脊液（CSF）的传输和压力调节。膜的紊乱可能会导致一些难以用动物模型复制的变化，这表明需要一种使用带有颗粒的人蛛网膜模型来研究诸如阿尔茨海默病、脑积水和假性脑瘤等病症。作者详细介绍了一种体外模型的开发和验证，该模型用于模拟脑脊液通过人蛛网膜颗粒（AGs）流出的体内情况。
在正常生理压力下，以生理和非生理方向灌注人AGs以获取通透性数据。通过电子显微镜进行荧光颗粒灌注，确定通过AGs的流出途径。
这种人源体外模型展示出了体内单向性、颗粒运输和超微结构等特性，与我们2005年的体外模型相似。在统计学上等效的平均正常生理压力（分别为5.88±0.22 mmHg和6.14±0.23 mmHg）下，生理方向（n = 20）的平均基线水力传导率为1.05±0.15 μL/min/mm Hg/cm²，而非生理方向（n = 3）为0.11±0.03 μL/min/mm Hg/cm²（P = 0.46）。
体外模型是可行的，本文已予以证明。这些发现与体内脑脊液流出情况相符。该模型不仅增加了对脑脊液清除的理解，还增进了对通过蛛网膜清除代谢物的理解。其他证据表明，但尚未证明，除了通过AGs的流动外，脑脊液流出可能以类似方式发生在颗粒附近的蛛网膜中。这是一个有待进一步研究的课题。
