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Author ORCID Identifier
https://orcid.org/0000-0002-2165-771X
AccessType
Open Access Dissertation
Document Type
dissertation
Degree Name
Doctor of Philosophy (PhD)
Degree Program
Chemical Engineering
Year Degree Awarded
2024
Month Degree Awarded
February
First Advisor
Shelly R Peyton
Subject Categories
Biomechanics and Biotransport
Abstract
Cavitation, or the formation and collapse of bubbles, is an important phenomenon to study in soft tissues since cavitation is a damage mechanism implicated in both concussive and blast-associated traumatic brain injury (TBI). More than 1.7 million people suffer from TBI in the U.S. every year, and 5.3 million suffer from TBI-related disabilities. Brain mechanics play an essential role in the propagation of cavitation-related damage in vivo, but the heterogeneous, complex nature of brain tissues makes it particularly difficult to characterize. I use cavitation to quantify brain mechanics and measure cavitation-related tissue and cellular damage in mild TBI. I use needle-induced cavitation (NIC) to create a single bubble in ex vivo mouse brain at specific locations and measure the pressure associated with a cavitation event, which is used to calculate a localized modulus. Local and distant cavitation damage indicates that cavitation sometimes expands through fracture along interfaces between regions. I use my experimental NIC fracture data with hydraulic fracture models to estimate brain tissue fracture energy, which has never been measured in intact brain tissue and will aid in understanding how cavitation damage propagates through brain. There is a lack of TBI models that relate injury forces to macroscale tissue damage and brain function at the cellular level. We use NIC as a mild TBI model in the hippocampus to measure the impact of injury on synaptic signaling and astrocyte specific extracellular matrix remodeling. Using patch-clamp electrophysiology, we demonstrate that injury in the hippocampus temporarily decreases synaptic activity in a cannabinoid 1 receptor-dependent manner. Further, we show that NIC induces an increase in astrocyte activation and upregulation of astrocyte secreted extracellular matrix proteins associated with neural repair 72 hours after injury. NIC provides a valuable tool to study real time neuronal response to small- scale injuries and understand how mild TBI impacts neural function at the cellular level in the seconds, minutes, and days following injury. This research lays the groundwork to unravel cellular mechanisms post-TBI to develop treatments that promote neural repair in response to brain injury and prevent neurodegeneration for concussion and blast wave victims.
DOI
https://doi.org/10.7275/36070818
Recommended Citation
Dougan, Carey E., "QUANTIFYING BRAIN MECHANICS AND RESPONSE TO CAVITATION- INDUCED MILD TRAUMATIC BRAIN INJURY" (2024). Doctoral Dissertations. 3044.
https://doi.org/10.7275/36070818
https://scholarworks.umass.edu/dissertations_2/3044
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.