Ex vivo Model of Cerebrospinal Fluid Outflow across Human Arachnoid Granulations
Shelley A. Glimcher 1,
David W Holman 1,
Martin Lubow 2,
and
Deborah M. Grzybowski 3*
1 Ophthalmology & Biomedical Engineering, The Ohio State University, Columbus, Ohio, United States
2 Ophthalmology, The Ohio State University, Columbus, Ohio, United States
3 Ophthalmology & Biomedical Engineering, The Ohio State University, Columbus, Ohio, United States; Ophthalmology, The Ohio State University, Columbus, Ohio, United States
* To whom correspondence should be addressed. E-mail: grzybowski.3{at}osu.edu.
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Abstract |
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Objective
The brain,s arachnoid membrane with granulations is an important biological barrier whose responsibilities include transmission of cerebrospinal fluid (CSF), and regulation of pressure. Membrane disturbance may cause changes difficult to replicate with animal models, suggesting need for a model using human arachnoid membrane with granulations for study of diseases such as Alzheimer,s, hydrocephalus, and pseudotumor cerebri. We 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 physiologic pressures 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 in vitro model. The average baseline hydraulic conductivity in the physiological direction (n=20) was 1.05±0.15µL/min/mmHg/cm2 versus 0.11 ±0.03µL/min/mmHg/cm2 in the nonphysiological direction (n=3) under statistically equivalent (p=0.46) average normal physiological pressures (5.88±0.22mmHg and 6.14±0.23mmHg respectively).
Interpretation
The ex vivo model is feasible and herein demonstrated. These findings agree with in vivo CSF outflow. This model increases our understanding of the clearance not only of CSF, but also of metabolites through the arachnoid membrane. Additional evidence suggests, but does not as yet prove, that CSF outflow may occur in a similar manner in the adjacent arachnoid membrane, as well as through the AGs. This is another topic of our further investigation.
Key Words:
neuroophthalmology, hydraulic conductivity, arachnoid granulations, Idiopathic Pseudotumor Cerebri, CSF outflow, intracranial pressure
