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Originally published In Press as doi:10.1167/iovs.08-2238 on July 9, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:4721-4728.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.08-2238
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Ex Vivo Model of Cerebrospinal Fluid Outflow across Human Arachnoid Granulations

Shelley A. Glimcher,1,2 David W. Holman,1,2 Martin Lubow,2 and Deborah M. Grzybowski1,2

1From the Department of Biomedical Engineering and the 2Neurovascular Research Group, Department of Ophthalmology, The Ohio State University, Columbus, Ohio.

PURPOSE. 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.

METHODS. 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.

RESULTS. 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 µL/min/mm Hg/cm2 compared with 0.11 ± 0.03 µL/min/mm Hg/cm2 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).

CONCLUSIONS. 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.






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