Cerebrospinal fluid dynamics in the human cranial subarachnoid space: an overlooked mediator of cerebral disease. II.
            In vitro
            arachnoid outflow model

Holman, David W.; Kurtcuoglu, Vartan; Grzybowski, Deborah M.

doi:10.1098/rsif.2010.0032

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Journal article

Cerebrospinal fluid dynamics in the human cranial subarachnoid space: an overlooked mediator of cerebral disease. II.
In vitro
arachnoid outflow model

Holman, David W. Ophthalmology Research Division, Ohio State University, 915 Olentangy River Road, Columbus, OH 43212, USA
Kurtcuoglu, Vartan Laboratory of Thermodynamics in Emerging Technologies, Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland
Grzybowski, Deborah M. Ophthalmology Research Division, Ohio State University, 915 Olentangy River Road, Columbus, OH 43212, USA

2010-3-24

Published in:

Journal of The Royal Society Interface. - The Royal Society. - 2010, vol. 7, no. 49, p. 1205-1218

English
The arachnoid membrane (AM) and granulations (AGs) are important in cerebrospinal fluid (CSF) homeostasis, regulating intracranial pressure in health and disease. We offer a functional perspective of the human AM's transport mechanism to clarify the role of AM in the movement of CSF and metabolites. Using cultures of human AG cells and a specialized perfusion system, we have shown that this
in vitro
model mimics the
in vivo
characteristics of unidirectional fluid transport and we present the first report of serum-free permeability values (92.5 µl min
−1
mm Hg
−1
cm
−2
), which in turn are in agreement with the CSF outflow rates derived from a dynamic,
in vivo
magnetic resonance imaging-based computational model of the subarachnoid cranial space (130.9 µl min
−1
mm Hg
−1
cm
−2
). Lucifer yellow permeability experiments have verified the maintenance of tight junctions by the arachnoidal cells with a peak occurring around 21 days post-seeding, which is when all perfusion experiments were conducted. Addition of ruthenium red to the perfusate, and subsequent analysis of its distribution post-perfusion, has verified the passage of perfusate via both paracellular and transcellular mechanisms with intracellular vacuoles of approximately 1 µm in diameter being the predominant transport mechanism. The comparison of the computational and
in vitro
models is the first report to measure human CSF dynamics functionally and structurally, enabling the development of innovative approaches to modify CSF outflow and will change concepts and management of neurodegenerative diseases resulting from CSF stagnation.

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