Response of Astrocytes to Blood Exposure due to Shunt Insertion in vitro

Abstract

The breakdown of the ventricular zone (VZ) with the presence of blood in cerebrospinal fluid (CSF) has been shown to increase shunt catheter obstruction in the treatment of hydrocephalus, but the mechanisms by which this occurs are generally unknown. Using a custom-built incubation chamber, we immunofluorescently assayed cell attachment and morphology on shunt catheters with and without blood after 14 days. Samples exposed to blood showed significantly increased cell attachment (average total cell count 392.0±317.1 versus control of 94.7±44.5, P<0.0001). Analysis of the glial fibrillary acidic protein (GFAP) expression showed similar trends (854.4±450.7 versus control of 174.3±116.5, P<0.0001). An in vitro model was developed to represent the exposure of astrocytes to blood following an increase in BBB permeability. Exposure of astrocytes to blood increases the number of cells and their spread on the shunt.

The effect of A1 and A2 reactive astrocyte expression on hydrocephalus shunt failure

“…Targeted therapies that inhibit astrocyte cell activation were able to significantly reduce astrocyte cell adhesion on PDMS coated surfaces mimicking the shunt surface. These results are in accordance with other studies indicating that the knockout of reactive astrocyte activating factors slows disease progression [ 33 ], dampening the formation of reactive astrocytes prevents neuronal death [ 36 ], and astrogliosis inhibition attenuates hydrocephalus [ 40 , 41 ]. TGF-ß suppresses A1 astrocyte activation [ 8 ], reverses the formation of A1 astrocytes by fibroblast growth factor (FGF) signaling [ 42 ], and greatly reduces the expression of A1-specific markers [ 43 ].…”