Every year millions of individuals suffer from traumatic brain injury (TBI) leading to permanent disabilities and even death. Mild TBI (mTBI) is the most common form of TBI comprising about 80-90% of all occurrences. Following a CNS insult like an mTBI, astrocytes can undergo activation resulting in the transformation into reactive astrocytes (RAs). RAs also play an important role in brain remodeling following an mTBI. Research on the mechanical complexity of the brain has important implications for understanding brain function and dysfunction, as well as for the development of new diagnostic and therapeutic tools for neurological disorders. This study aimed to develop and utilize an emph{in vitro} mTBI platform to investigate the intricate mechanical interplay between the extracellular matrix (ECM) and astrocytes following a simulated mTBI. Cellular mechanisms underlying mTBI and the contribution of mechanical forces that result in prolonged brain damage are yet to be comprehensively understood. Successfully devised mechanical characterization techniques for tissue-engineered models were developed utilizing atomic force microscopy and rheology. Astrocyte exposure to high-rate overpressure revealed altered mechanical properties of the surrounding matrix and decreased expression of laminin and collagen IV, which are critical for brain function and may contribute to pathologies associated with mTBI. The developed platform and methods provide new insights into the mechanistic complexity underlying ECM-astrocyte interactions following an mTBI. / Master of Science / Every year, millions of people suffer from traumatic brain injury (TBI), which can lead to permanent disabilities or even death. The most common form of TBI is mild TBI (mTBI), which accounts for 80-90% of all cases. After a mTBI, astrocytes, the most common cell type in the brain, can become activated and turn into reactive astrocytes (RAs). RAs play an important role in the brain's recovery following a mTBI. Understanding the mechanical complexity of the brain is crucial for developing new diagnostic and therapeutic tools for neurological disorders. This study aimed to investigate the mechanical interplay between the modeled tissue and astrocytes following a simulated mTBI using an emph{in vitro} platform. Development of mechanical characterization techniques allowed for any alterations caused by the astrocytes to their environment to be detectable. The astrocyte exposure to the simulated mTBI revealed altered mechanical properties of the surrounding environment and decreased expression of proteins laminin and collagen IV, which are critical to brain function and may contribute to pathologies associated with mTBI. This study provides new insights into the mechanistic complexity underlying the interaction between astrocytes and their environment, which could lead to the development of new treatments.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/115747 |
| Date | 11 July 2023 |
| Creators | Al-Jaouni, Laith |
| Contributors | Department of Biomedical Engineering and Mechanics, Verbridge, Scott, Korneva, Arina, VandeVord, Pamela J. |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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