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A computational model of cerebrospinal fluid production and reabsorption driven by Starling forces.

Buishas J, Gould IG, Linninger AA - Croat. Med. J. (2014)

Bottom Line: This model investigates the effect of osmotic pressure on water transport between the cerebral vasculature, the extracellular space (ECS), the perivascular space (PVS), and the CSF.Investigations into the effect of osmotic pressure on the volume of ventricles and the flux of ions in the blood, choroid plexus epithelium, and CSF are reviewed.Water flux from the ECS to the CSF is identified as a key feature of intracranial dynamics.

View Article: PubMed Central - PubMed

Affiliation: Andreas A. Linninger, Professor of Chemical Engineering and Bioengineering, University of Illinois at Chicago, Laboratory for Product and Process Design, M/C 063, 851 S. Morgan St. - 218 SEO, Chicago, Illinois 60607-7000, linninge@uic.edu.

ABSTRACT
Experimental evidence has cast doubt on the classical model of river-like cerebrospinal fluid (CSF) flow from the choroid plexus to the arachnoid granulations. We propose a novel model of water transport through the parenchyma from the microcirculation as driven by Starling forces. This model investigates the effect of osmotic pressure on water transport between the cerebral vasculature, the extracellular space (ECS), the perivascular space (PVS), and the CSF. A rigorous literature search was conducted focusing on experiments which alter the osmolarity of blood or ventricles and measure the rate of CSF production. Investigations into the effect of osmotic pressure on the volume of ventricles and the flux of ions in the blood, choroid plexus epithelium, and CSF are reviewed. Increasing the osmolarity of the serum via a bolus injection completely inhibits nascent fluid flow production in the ventricles. A continuous injection of a hyperosmolar solution into the ventricles can increase the volume of the ventricle by up to 125%. CSF production is altered by 0.231 μL per mOsm in the ventricle and by 0.835 μL per mOsm in the serum. Water flux from the ECS to the CSF is identified as a key feature of intracranial dynamics. A complete mathematical model with all equations and scenarios is fully described, as well as a guide to constructing a computational model of intracranial water balance dynamics. The model proposed in this article predicts the effects the osmolarity of ECS, blood, and CSF on water flux in the brain, establishing a link between osmotic imbalances and pathological conditions such as hydrocephalus and edema.

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Related in: MedlinePlus

Simplified illustration depicting both the classical and the microvessel hypothesis. The choroid plexus actively creates an ionic concentration gradient between the blood and the ventricles, which drives water transport. The cerebrospinal fluid (CSF) then flows through the ventricles, where it is absorbed through the arachnoid granulations (AG) into the superior sagittal sinus (SSS). CSF is produced and reabsorbed by the capillaries in the parenchyma due to an imbalance in hydrostatic and osmotic pressure, known as Starling force.
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Figure 1: Simplified illustration depicting both the classical and the microvessel hypothesis. The choroid plexus actively creates an ionic concentration gradient between the blood and the ventricles, which drives water transport. The cerebrospinal fluid (CSF) then flows through the ventricles, where it is absorbed through the arachnoid granulations (AG) into the superior sagittal sinus (SSS). CSF is produced and reabsorbed by the capillaries in the parenchyma due to an imbalance in hydrostatic and osmotic pressure, known as Starling force.

Mentions: The classical hypothesis postulates that the choroid plexus epithelium, located in the ventricles, actively secretes CSF. The choroid plexus is composed of specialized epithelial cells that contain mitochondria, which are joined together via tight junctions. Membrane-bound transporters of Na+, K+, Cl-, and HCO3- ions on both the apical (CSF facing) and basolateral (blood facing) surface of the choroid plexus epithelium create a concentration gradient. This gradient drives water filtration from the fenestrated arterials feeding the choroid plexus into the CSF in the ventricles (5,6). In the classical view, newly formed CSF flows to the subarachnoid space where it passes through the arachnoid granulations into the superior sagittal sinus (SSS). The production of CSF and movement through the ventricles to the veins is illustrated in Figure 1.


A computational model of cerebrospinal fluid production and reabsorption driven by Starling forces.

Buishas J, Gould IG, Linninger AA - Croat. Med. J. (2014)

Simplified illustration depicting both the classical and the microvessel hypothesis. The choroid plexus actively creates an ionic concentration gradient between the blood and the ventricles, which drives water transport. The cerebrospinal fluid (CSF) then flows through the ventricles, where it is absorbed through the arachnoid granulations (AG) into the superior sagittal sinus (SSS). CSF is produced and reabsorbed by the capillaries in the parenchyma due to an imbalance in hydrostatic and osmotic pressure, known as Starling force.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4228294&req=5

Figure 1: Simplified illustration depicting both the classical and the microvessel hypothesis. The choroid plexus actively creates an ionic concentration gradient between the blood and the ventricles, which drives water transport. The cerebrospinal fluid (CSF) then flows through the ventricles, where it is absorbed through the arachnoid granulations (AG) into the superior sagittal sinus (SSS). CSF is produced and reabsorbed by the capillaries in the parenchyma due to an imbalance in hydrostatic and osmotic pressure, known as Starling force.
Mentions: The classical hypothesis postulates that the choroid plexus epithelium, located in the ventricles, actively secretes CSF. The choroid plexus is composed of specialized epithelial cells that contain mitochondria, which are joined together via tight junctions. Membrane-bound transporters of Na+, K+, Cl-, and HCO3- ions on both the apical (CSF facing) and basolateral (blood facing) surface of the choroid plexus epithelium create a concentration gradient. This gradient drives water filtration from the fenestrated arterials feeding the choroid plexus into the CSF in the ventricles (5,6). In the classical view, newly formed CSF flows to the subarachnoid space where it passes through the arachnoid granulations into the superior sagittal sinus (SSS). The production of CSF and movement through the ventricles to the veins is illustrated in Figure 1.

Bottom Line: This model investigates the effect of osmotic pressure on water transport between the cerebral vasculature, the extracellular space (ECS), the perivascular space (PVS), and the CSF.Investigations into the effect of osmotic pressure on the volume of ventricles and the flux of ions in the blood, choroid plexus epithelium, and CSF are reviewed.Water flux from the ECS to the CSF is identified as a key feature of intracranial dynamics.

View Article: PubMed Central - PubMed

Affiliation: Andreas A. Linninger, Professor of Chemical Engineering and Bioengineering, University of Illinois at Chicago, Laboratory for Product and Process Design, M/C 063, 851 S. Morgan St. - 218 SEO, Chicago, Illinois 60607-7000, linninge@uic.edu.

ABSTRACT
Experimental evidence has cast doubt on the classical model of river-like cerebrospinal fluid (CSF) flow from the choroid plexus to the arachnoid granulations. We propose a novel model of water transport through the parenchyma from the microcirculation as driven by Starling forces. This model investigates the effect of osmotic pressure on water transport between the cerebral vasculature, the extracellular space (ECS), the perivascular space (PVS), and the CSF. A rigorous literature search was conducted focusing on experiments which alter the osmolarity of blood or ventricles and measure the rate of CSF production. Investigations into the effect of osmotic pressure on the volume of ventricles and the flux of ions in the blood, choroid plexus epithelium, and CSF are reviewed. Increasing the osmolarity of the serum via a bolus injection completely inhibits nascent fluid flow production in the ventricles. A continuous injection of a hyperosmolar solution into the ventricles can increase the volume of the ventricle by up to 125%. CSF production is altered by 0.231 μL per mOsm in the ventricle and by 0.835 μL per mOsm in the serum. Water flux from the ECS to the CSF is identified as a key feature of intracranial dynamics. A complete mathematical model with all equations and scenarios is fully described, as well as a guide to constructing a computational model of intracranial water balance dynamics. The model proposed in this article predicts the effects the osmolarity of ECS, blood, and CSF on water flux in the brain, establishing a link between osmotic imbalances and pathological conditions such as hydrocephalus and edema.

Show MeSH
Related in: MedlinePlus