Date of Graduation

12-2016

Document Type

Thesis

Degree Name

Master of Science in Biomedical Engineering (MSBME)

Degree Level

Graduate

Department

Biomedical Engineering

Advisor

Jeffrey C. Wolchok

Committee Member

Kartik Balachandran

Second Committee Member

Woodrow Shew

Keywords

Biological sciences; Applied sciences; Astrocytes; Extracellular matrix; Glial scar; Repeat injury; Traumatic brain injury

Abstract

Following injury to the central nervous system, extracellular modulations are apparent at

the site of injury, often resulting in a glial scar. Astrocytes are mechanosensitive cells, which can create a neuroinhibitory extracellular environment in response to injury. The aim for this research was to gain a fundamental understanding of the affects a diffuse traumatic brain injury has on the astrocyte extracellular environment after injury. To accomplish this, a bioreactor culturing astrocytes in 3D constructs delivered 150G decelerations with 20% biaxial strain to mimic a traumatic brain injury. Experiments were designed to compare the potential effects of media type, number of impacts, and impacts with or without strain. Multiple impacts on astrocytes resulted in increased apoptosis, supporting cumulative effects of multiple traumatic brain injury events. Surprisingly, the expression of glial fibrillary acidic protein and S100B by astrocytes was downregulated following injury. With multiple impacts, astrocytes downregulated collagen and glycosaminoglycan expression at acute time points. Suppression of matrix metalloproteinase-2 coupled with unchanging production of transforming growth factor beta-1 and tissue inhibitor of metalloproteinase-1 indicates an inability to degrade damaged ECM or produce new ECM. This was supported by long-term studies which indicate significant decreases in chondroitin sulfate proteoglycan and collagen I accumulation. This could suggest astrocytes experiencing damaging mechanical stimulation enter a survival state ceasing to moderate the extracellular environment at short time points after injury.

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