Devrim Kilinc, MS
Advisors: Ken Barbee, Ph.D and Gianluca Gallo, Ph.D.
Brain injury following mechanical trauma is believed to be due to direct physical injury to axons. Secondary injury involves a complex sequence of cellular events, ultimately leading to axonal beading, disconnection from target tissues, and cell death. In vitro traumatic axonal injury models have been extensively studied to understand various aspects of human traumatic brain injury and to develop potential treatment strategies. Among these, fluid shear stress injury model is remarkable since it enables precise control over the rate and magnitude of the insult and brings the ability to observe cells before, during and after the injury. Our study will be the first to utilize this model with primary neuron culture, which provides a better model system by using central nervous system neurons, obtained from embryonic chick forebrain. Using micro-patterned coverslips, individual neurons will be traced during the experiment as well as after fixation and immuno-staining. This way, direct evidence between post-injury morphology and post-injury cytoskeleton (CSK) structure will be obtained. This is especially important in understanding the exact mechanisms of secondary injury, including the roles played by axolemma, CSK proteins, calcium and Calpains.
This study will investigate the role played by calcium and calcium-dependent proteases, as well as the mechanism by which calcium enters the axon. The neuroprotective ability of Poloxamer 188 via resealing mechanically-induced membrane pores will also be investigated. We aim to design and develop a novel microfluidic flow chamber that will enable us to conduct isolated and strictly localized insults to an axon segment. Isolated insults and corresponding axonal response is aimed to mimic TAI and therefore extend our understanding of focal axonal developments that eventually lead to impairment of transport, generation of beads, and subsequent disconnection.
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