(Dr. Robert Cargill, advisor)

"A Novel In Vitro Shear Device for High Strain Rate Injury of 3-D Neural Cell Cultures"

Abstract

 In order to understand the chemical and molecular cascades that occur in traumatic brain injury (TBI), it is important to model the mechanical and biochemical aspects of this injury as accurately as possible.  A custom designed device capable of large shear strain (up to 50%), and high strain rates (up to 100s) was constructed in order to determine the impact of shearing effects on 3-D neural cell cultures.  A number of 2-D in vitro models of TBI, such as membrane deformation and fluid shear stress have been developed.  However, these models are limited in their ability to mimic the structural complexity of the brain, given that the cells in situ are in a 3-D configuration.  Also, it has been shown that cells in 3-D culture exhibit gene expression and drug sensitivity, and survival more similar to in vivo preparations than 2-D cultures.  Therefore, in using 3-D cultures it is hypothesized that this apparatus will provide ad more accurate in vitro model of TBI.  This system uses two plates with direct attachment to the culture to provide accurate control over the amount of induced deformation.  The bottom plate remains fixed while the top plate induces shear deformation by its controlled relative displacement.  The system will be used to examine real-time and long-term post injury cellular outcome on 3-D cell cultures using confocal microscopy.