Date on Master's Thesis/Doctoral Dissertation
8-2023
Document Type
Doctoral Dissertation
Degree Name
Ph. D.
Department
Interdisciplinary and Graduate Studies
Degree Program
Interdisciplinary Studies with a specialization in Translational Neuroscience, PhD
Committee Chair
Magnuson, David
Committee Co-Chair (if applicable)
Whittemore, Scott
Committee Member
Whittemore, Scott
Committee Member
Samuelsen, Chad
Committee Member
Ding, Dale
Committee Member
Jones, Kathryn
Author's Keywords
Propriospinal; neurons; neuroanatomy; gene therapy; plasticity
Abstract
This dissertation is an examination of spinal cord injury induced neuroplasticity and tests whether noninvasive gene therapy can successfully target neurons in the lumbar spinal cord. It begins with an overview of neural control of locomotion and a brief summary of therapeutics that are used and/or in development for treating spinal anatomically characterize s subset of neurons in the spinal cord, long ascending propriospinal neurons, that are involved in interlimb coordination. Characterization of these neurons allows for subsequent evaluation of their potential involvement in injury induced neuroplasticity. This dissertation is divided into five chapters, covering spinal cord injury and therapeutics. Chapter One gives background on locomotor control, propriospinal neurons, spinal cord injury, and therapeutics. Chapter Two develops and characterizes viral tracing methods for spinal cord anatomy. Chapter Three then uses these methods to characterize long ascending propriospinal neurons and evaluate their involvement in injury induced plasticity. Chapter Four then focuses on the development of noninvasive delivery of gene transfer to the lumbar enlargement. This involves optimizing focused ultrasound and intravenous microbubble delivery to focally and transiently permeabilize the blood spinal cord barrier of the lumbar spinal cord. This optimization then allows for successful gene transfer in neurons in the lumbar spinal cord following intravenous delivery of viral vector. Lasty, Chapter Five discusses the implications for all of these findings and how these findings have contributed to our understanding spinal cord anatomy and injury, and how the proof-of-concept in Chapter 4 provides a promising new avenue for spinal cord injury therapeutics.
Recommended Citation
Brown, Brandon Lee, "Injury induced neuroplasticity and cell specific targeting of the lumbar enlargement for gene therapy." (2023). Electronic Theses and Dissertations. Paper 4141.
https://doi.org/10.18297/etd/4141
