title: Ex vivo model of cerebrospinal fluid outflow across human arachnoid granulations.
abstract: OBJECTIVE
  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 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).
  
  
  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.
authors.affiliation: Department of Biomedical Engineering, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Glimcher
authors.forename: David W
authors.initials: DW
authors.lastname: Holman
authors.forename: Martin
authors.initials: M
authors.lastname: Lubow
authors.forename: Deborah M
authors.initials: DM
authors.lastname: Grzybowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001099:Arachnoid / Q000378:metabolism* / Q000648:ultrastructure; D002102:Cadaver; D002463:Cell Membrane Permeability; D002470:Cell Survival; D002478:Cells, Cultured; D002555:Cerebrospinal Fluid / Q000502:physiology*; D019084:Fluorescent Antibody Technique, Indirect; D006097:Granulation Tissue / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010477:Perfusion