Description
- Abstract:
- The successful detection and prevention of traumatic brain injuries relies on the quantitative identification of cellular injury thresholds associated with the underlying cellular pathology. First, a 3D in vitro cell culture platform will be described capable of being reproducibly mechanically deformed and efficiently immunolabeled for cytoskeletal markers of interest in diverse neural cell structures. This work will then combine recently developed inertial microcavitation rheology techniques with a 3D in vitro collagen-I hydrogel-based neural tissue model to provide the first quantitative experimental mechanical injury tolerance thresholds for neural cells at strain rates on the order of 10^3-10^8 1/s. In this work the structural pathology of neural cells following inertial cavitation-induced mechanical deformations are resolved to allow for the quantification of critical injury strain thresholds of neural cell populations occurring at high loading rates such as those encountered in blast, cavitation or directed energy exposures. Specific thresholds for cellular projections are determined and indicate that neuronal dendritic spines characterized by MAP2 display the lowest physical failure strain at 7.3%, whereas general neural cellular projections containing microtubules and filamentous actin were able to tolerate appreciably higher strains (14%) prior to injury. Interestingly, while these critical injury thresholds were similar to previous literature values reported for moderate and lower strain rates (< 100 1/s), the pathology of primary injury reported here was distinctly different by being purely physical in nature as compared to biochemical activation during apoptosis or necrosis. The work concludes with the discussion and examination of primary mechanical injury in an integrin-rich hydrogel substrate to inform the future extension of high-rate mechanical neural cell injury to the regime of secondary biochemical injury activation through more diverse mechanotransduction pathways.
- Notes:
- Thesis (Ph. D.)--Brown University, 2021
Citation
Cramer III, Harry Calvin,
"Extracting Primary Mechanical Neural Cellular Injury Thresholds Following High-rate Mechanical Deformations"
(2021).
Biomedical Engineering Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://repository.library.brown.edu/studio/item/bdr:b3c473nx/
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Biomedical Engineering Theses and Dissertations
Theses and Dissertations for the Biomedical Engineering department....