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Biomechanics of Traumatic Brain Injury in vitro and the Neuroprotective Effects of Mild Hypothermia Post-Injury


The underlying cellular mechanisms of traumatic brain injury (TBI) are both complex and poorly understood, resulting in no widely agreed-upon treatments and unreliable diagnosis strategies. This thesis will focus on my research efforts in 1) understanding the role of strain and strain rate on in vitro neural injury, and 2) investigating the efficacy of therapeutic hypothermia (TH) treatment with the aforementioned biomechanical injury space in mind. First the 3D, in vitro neural compression model and the related imaging and analysis techniques used are described. I show that strain rate influences the morphological signature of injury and that strain magnitude predicts the time of neuronal death. With this established therapeutic intervention window in mind, the effects of TH treatment on injured neural cells is discussed. TH has long been considered an attractive treatment strategy for TBIs. However, inconsistencies in clinical methods have contributed to a general disagreement over its efficacy. I found that TH, when administered at the right temperature, time duration, and within a critical time window, proves highly effective in maintaining neural health. Furthermore, beneficial effects on two neurodegenerative pathways are shown. Finally, two pilot studies are shown: adapting the in vitro system for tension loading; and adapting the compression injury system for injuring self-assembled neural spheroids. These results provide important insights into the cellular mechanisms of TBI and the practical deployment of TH.
Thesis (Ph. D.)--Brown University, 2019

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Scimone, Mark T., "Biomechanics of Traumatic Brain Injury in vitro and the Neuroprotective Effects of Mild Hypothermia Post-Injury" (2019). Biomedical Engineering Theses and Dissertations. Brown Digital Repository. Brown University Library.