Investigation of Microcavitation in 3D in-vitro Models of Blast Traumatic Brain Injury
Abstract
Investigation of Microcavitation in 3D in-vitro Models of Blast Traumatic Brain InjuryCavitation, the formation and collapse of vapor bubbles inside a liquid medium, is one of the most powerful and devastating damage mechanisms that exist in the world. While cavitation damage has been studied in detail for engineering application, there is recent emerging evidence that cavitation occurs in the human brain during blast-induced trauma [1-5]. However the molecular mechanism and the structural damage features of cavitation at the cellular level are poorly understood [5, 6]. Yet this information is critically important, since the clinical effects of TBI initiate in signaling cascades at the single cell level [7-9].This proposal details the design and execution of a series of quantitative experiments to investigate thedynamic interaction of cavitation bubbles with cortical neurons, astrocytes and microglia in three physiologically-distinct, three-dimensional (3D) in-vitro environments. Recent completed work by ourlaboratory has led to the development of two significant experimental advances for investigating microcavitation in neurons. First, we developed a robust, high-resolution experimental apparatus for inducing microcavitation inside 3D neuronal cultures and brain phantom materials using a focused infrared laser. Second, we have been developing the first, 3D spectrally-assisted DigitalImage Correlation method for measuring cavitation-induced material strains and strain rates experimentally. This setup is currently being finalized, and once complete will provide the first direct material and neuronal strain estimates due to microcavitation.Utilizing the unique experimental capability that we generated under the previous award, we will (i)systematically investigate the spatiotemporal pathophysiology of microcavitation in 3D neuronalcultures of increasingly heightened physiological relevance, and (ii) detail the conditions of strain,strain rate, and strain modality under which injury is produced. It is anticipated that the results from this work will provide significant cellular details of cavitation in thebrain and its underpinning molecular and structural damage mechanism. This information is criticallyneeded to understand the role cavitation plays in the brain as an injury mechanism and whether thisinjury mechanism shares molecular similarities with diffuse axonal injury due to blunt trauma. Furthermore, this proposal in particular addresses the role of astrocytes and microglia during the injury progression due to cavitation, which significantly increases the physiological relevance of the proposed work. Taken together, it is anticipated that the results from this work will play a crucial role in guiding the design of tissue level in-vitro and in particular in-vivo studies focusing on microcavitation as a potential injury mechanism in blast traumatic brain injuries.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Sep 30, 2016
- Source ID
- N000141612872
Entities
People
- Christian Franck
Organizations
- Brown University
- Office of Naval Research
- United States Navy