Enhanced wall shear stress prevents obstruction by astrocytes in ventricular catheters

Abstract

The treatment of hydrocephalus often involves the placement of a shunt catheter into the cerebrospinal ventricular space, though such ventricular catheters often fail by tissue obstruction. While diverse cell types contribute to the obstruction, astrocytes are believed to contribute to late catheter failure that can occur months after shunt insertion. Using in vitro microfluidic cultures of astrocytes, we show that applied fluid shear stress leads to a decrease of cell confluency and the loss of their typical stellate cell morphology. Furthermore, we show that astrocytes exposed to moderate shear stress for an extended period of time are detached more easily upon suddenly imposed high fluid shear stress. In light of these findings and examining the range of values of wall shear stress in a typical ventricular catheter through computational fluid dynamics (CFD) simulation, we find that the typical geometry of ventricular catheters has low wall shear stress zones that can favour the growth and adhesion of astrocytes, thus promoting obstruction. Using high-precision direct flow visualization and CFD simulations, we discover that the catheter flow can be formulated as a network of Poiseuille flows. Based on this observation, we leverage a Poiseuille network model to optimize ventricular catheter design such that the distribution of wall shear stress is above a critical threshold to minimize astrocyte adhesion and growth. Using this approach, we also suggest a novel design principle that not only optimizes the wall shear stress distribution but also eliminates a stagnation zone with low wall shear stress, which is common to current ventricular catheters.

Slippery Liquid-Like Solid Surfaces with Promising Antibiofilm Performance under Both Static and Flow Conditions

“…These stresses were at least one order of magnitude higher than those found in medical devices (e.g., catheters). 57 …”

“…The samples were then removed from the flow chamber for subsequent imaging using a fluorescent microscope (Olympus, BX-61). According to eqs 1 and 2 , the resulting wall shear stress (τ w ) at 37 °C ranged from 0.007 to 0.105 Pa, which corresponds to similar wall shear stress in catheters (a few mPa) 57 and was extended to over an order of magnitude higher to observe trends of biofilm detachment.…”

A high-resolution real-time quantification of astrocyte cytokine secretion under shear stress for investigating hydrocephalus shunt failure

“…Most of the CSF volume flows through the proximal holes of the shunt’s ventricular catheter, i.e., holes located furthest from the tip of the shunt with less resistance to flow. Computational fluid dynamics simulations have shown that in CSF shunts, the wall shear stress at the proximal holes is greater than 0.5 dyne/cm 2 10 – 12 . This fact increases the shear stress at the proximal segment and is a key driver of a dense glial scar formation around devices causing failure via obstruction 11 , 13 , 14 .…”

Distortion of the Intracranial Pressure Waveform by Extraventricular Drainage System

“…Deionized water was used to fill the acrylic chamber and the EVD and EVS tubing instead of CSF. The assumption of water as a good substitute for normal CSF was based on the grounds of normal CSF acting like a Newtonian fluid with shear viscosity similar to that of water over a wide range of shear stresses [22]. This may be a poor assumption in active bleeding and hemorrhagic strokes when the CSF protein and cell counts are increased, which will require further investigation.…”