Brown University

Microcavitation as a neural cell damage mechanism in an in vitro model of blast traumatic brain injury

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Abstract:
Blast traumatic brain injury is a serious type of injury in the armed forces and considered the signature injury of the wars in Iraq and Afghanistan. While compressive hydrostatic pressures resulting from blast waves have been investigated, negative pressures resulting from the blast wave and wave-brain tissue interaction have the potential to nucleate bubbles in the nearly-incompressible tissue, leading to a separate damage mechanism of inertial cavitation. The specific relation between the mechanics of inertial cavitation and primary cell injury, to date, has not been investigated in detail. While inertial cavitation damage to free surfaces has been well-studied in the field of fluid dynamics, bubble interactions within 3D neural cultures and hydrogels are in their infancy, particularly experimentally. With the goal of quantifying the specific effects of inertial microcavitation as the proposed cellular injury mechanism in blast traumatic brain injury, presented here is an experimental approach of initiating inertial microcavitation in primary dissociated 3D neural cultures coupled with a new analysis technique for computing the critical local strains and stresses around cells that are found to induce cellular injury and mechanical disruption. Bubble dynamics during injury are quantified using high-speed imaging and custom image processing algorithms, while laser scanning confocal microscope image stacks of neurons before and after cavitation injury correlate bubble kinematics to fragmentation and disruption of cytoskeletal proteins. To get the high-rate constitutive behavior of the surrounding matrix, and subsequently spatiotemporal strains, strain rates, and stresses on the cells during cavitation, an approach called inertial microcavitation-based ultra-high-strain rate rheometry (IMUR) is presented as a new theoretical-numerical technique to assess local rheological properties of soft materials.
Notes:
Thesis (Ph. D.)--Brown University, 2017

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Citation

Estrada, Jonathan Bartholomew, "Microcavitation as a neural cell damage mechanism in an in vitro model of blast traumatic brain injury" (2017). Mechanics of Solids Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z0028PZM

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