Abstract
BackgroundShunt obstruction in the treatment of hydrocephalus is poorly understood, is multi-factorial, and in many cases is modeled ineffectively. Several mechanisms may be responsible, one of which involves shunt infiltration by reactive cells from the brain parenchyma. This has not been modeled in culture and cannot be consistently examined in vivo without a large sample size.MethodsWe have developed and tested a three-dimensional in vitro model of astrocyte migration and proliferation around clinical grade ventricular catheters and into catheter holes that mimics the development of cellular outgrowth from the parenchyma that may contribute to shunt obstruction.ResultsCell attachment and growth was observed on shunt catheters for as long as 80 days with at least 77 % viability until 51 days. The model can be used to study cellular attachment to ventricular catheters under both static and pulsatile flow conditions, which better mimic physiological cerebrospinal fluid dynamics and shunt system flow rates (0.25 mL/min, 100 pulses/min). Pulsatile flow through the ventricular catheter decreased cell attachment/growth by 63 % after 18 h. Under both conditions it was possible to observe cells accumulating around and in shunt catheter holes.ConclusionsAlone or in combination with previously-published culture models of shunt obstruction, this model serves as a relevant test bed to analyze mechanisms of shunt failure and to test catheter modifications that will prevent cell attachment and growth.
Highlights
Shunt obstruction in the treatment of hydrocephalus is poorly understood, is multi-factorial, and in many cases is modeled ineffectively
The mechanical integrity of alginate scaffolds was measured to compare the modulus of our constructs with that reported for human brain parenchyma
scanning electron microscope (SEM) was used to assess the alginate hydrogel structure, pore size and structure, to determine if these measurements were consistent with cell attachment and migration through the hydrogel to the catheter surfaces
Summary
Shunt obstruction in the treatment of hydrocephalus is poorly understood, is multi-factorial, and in many cases is modeled ineffectively. Several mechanisms may be responsible, one of which involves shunt infiltration by reactive cells from the brain parenchyma. This has not been modeled in culture and cannot be consistently examined in vivo without a large sample size. While the mechanisms causing ventricular catheter shunt obstruction and down-stream shunt valve obstruction are likely multi-faceted, inflammatory cells certainly play a major role in shunt obstruction in pediatric and adult patients. Perhaps mechanisms including single cell attachment, attachment of migrating and/or proliferating cells suspended in CSF, and/or attachment of activated glia from the brain parenchyma contribute to inflammatory-derived shunt obstruction. An activated response of astrocytes and microglia is likely to be involved through repair processes stimulated bycatheter insertion and continued catheter presence (i.e. a “foreignbody” response)
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