| Start Date: | 12/16/2016 | Start Time: | 9:30 AM |
| End Date: | 12/16/2016 | End Time: | 11:30 AM |
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Event Description
BIOMED PhD Research Proposal
Title:
Mechanistic Study of In Vitro Dynamic Stretch-induced Neural Injury
Speaker:
Zhengchen Su, PhD Candidate, School of Biomedical Engineering, Science and Health Systems
Advisor:
Ken Barbee, PhD, Professor and Interim Director, School of Biomedical Engineering, Science and Health Systems
Abstract:
There are approximately 2.5 million annual incidences of traumatic brain injury (TBI) in the United States, leading to substantial morbidity and mortality. TBI is induced by focal physical impact on the skull and/or dynamic stretching and shearing of the brain substance. In moderate and severe cases, TBI leads to neural degeneration and neuronal cell death, whose mechanism is not fully understood. Critical pathology involves transport impairment, mitochondria dysfunction, and calcium dysregulation, which link to the formation of focal swelling or beading, a morphological sign associated with transport impairment and the subsequent degeneration. Injured neurites lead to either further degeneration or gradual recovery, and therefore it is crucial to identify the important factors that determine the fate of the neurites.
Previous studies directly suggest two important factors, plasma membrane damage and mechanical breakage of microtubules, as being responsible for the early pathology. They are associated with microtubule depolymerization, calcium deregulation, dysfunctional mitochondria, and other structural protein damage. Therefore, they may also be critical to injury-induced neural degeneration. Meanwhile, limiting the secondary consequence of the accumulated damaged cellular content and dysfunctional organelles is the key to preventing further damage. Autophagy is an intrinsic mechanism for clearing damaged cellular content and dysfunctional organelles; however, its overactivation also leads to self-destruction. In the context of mechanical injury, the regulation and function of autophagy is unclear, given both harmful or protective roles have been reported in TBI models. Interestingly, membrane damage and microtubule disruption are also potential regulators for autophagic activity.
The goal of the proposed work is to elucidate how membrane disruption, microtubule depolymerization, and autophagic activity interactively contribute to neural degeneration. We utilize cell cultures of chicken forebrain neurons and take advantage of an in vitro silicone membrane stretch model to mimic the dynamic stretch aspect of traumatic brain injury. As a resulty, characteristic neural pathology can be reproduced. Several intervention and detection methods targeting membrane damage, microtubule disruption, and autophagy mechanisms will be applied to explore their linkage in the context of stretch injury. We expect that the membrane damage is a critical factor leading to neural degeneration due to its introduction of massive calcium influx triggering serious damage to the cellular proteins and organelles; autophagy is responsible for clearing and limiting dysfunction organelles, while its physiological function may be suppressed by certain consequences of membrane damage and microtubule disruption; and stabilizing microtubule may improve the autophagic flux and general cellular transport to attenuate the neural degeneration. |
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Location:
Bossone Research Center, Room 709, located at 32nd and Market Streets. |
Audience:
Undergraduate StudentsGraduate StudentsFacultyStaff |
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