Thesis Final Seth 4-28-21.pdf (3.38 MB)

ROLE OF ACROLEIN IN NEUROTRAUMA AND RELATED NEURODEGENERATION

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posted on 06.05.2021, 01:41 by Seth A HerrSeth A Herr
Neurotrauma is a general term describing injury to the central nervous system (CNS); which comprises of the brain and spinal cord. The damage resulting from neurotrauma includes primary injury, which occurs from different sources such as compressed air hitting the brain (bTBI) or an object/bone contusing the spinal cord, resulting in a spinal cord injury (SCI). These various means of primary brain and spinal cord injury are further complicated by the many possible combinations of severity levels and frequencies. However, primary injuries are regarded in many cases as unavoidable with the immediate nerve damage being largely irreversible. Despite all this, primary injuries of the CNS are related by common biochemical pathways in secondary injury. Secondary injury is the cause of declining outcomes after neurotrauma and poor recovery. Secondary injury begins immediately after primary injury and can continue to trigger death of neurons for years later. Given this contribution to poor recovery and its slow progression, secondary injury provides an excellent window of opportunity for therapeutic intervention. A major factor and key link in secondary injury and its perpetuation is reactive aldehyde formation, such as acrolein, from lipid peroxidation. The common formation of acrolein in neurotrauma is attributed to the unique structure of the CNS: with neurons containing a high lipid content from myelin and heavy metabolic activity they are vulnerable to acrolein formation. Thus, acrolein in secondary injury is a point of pathogenic convergence between the various forms of neurotrauma, and may play a role as well in the development of neurotrauma linked disorders and related neurodegeneration. The overall goal of this thesis is to therefore develop better strategies for acrolein removal. We explore here endogenous clearance strategies and targeted drug delivery in SCI, investigate detailed cellular structure changes in bTBI, and acrolein formation and removal in Parkinson’s disease. These findings of pathology, and effectiveness of new or existing acrolein removal strategies, will allow us to better employ treatments in future studies.

Funding

NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE (NINDS)

United States Department of Health and Human Services

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History

Degree Type

Doctor of Philosophy

Department

PULSe (Life Sciences)

Campus location

West Lafayette

Advisor/Supervisor/Committee Chair

Riyi Shi

Additional Committee Member 2

Amy Brewster

Additional Committee Member 3

Wei Zheng

Additional Committee Member 4

Richard Van Rijn

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