Advisory Committee Chair
Lucas Pozo-Miller
Advisory Committee Members
Shaida Andrabi
James A Bibb
Craig Powell
Charles Rosen
Document Type
Dissertation
Date of Award
2023
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Neurological injuries occur in epidemic proportions worldwide. Neuronal injuries are events resulting in damage to the central nervous system (CNS) that impair neurological function. Subsequent impairments in neuronal function can be rapid, existing immediately after injury, or progressive and chronic impairments that persist for the lifetime of the survivor. CNS injury constitutes a broad class of environmental and pathophysiological insults ranging from blunt-force trauma to the brain or spinal cord, to acute ischemic and hemorrhagic strokes, and insults resultant from neurotoxic agents. While divergent in initial cause, many of these insults share underlying pathophysiological outcomes including excitotoxic cell signaling, neuroinflammation, impaired cognition, damaged axonal transport, impaired mitochondrial function, generation of reactive oxygen species (ROS), disrupted neuronal connectivity, and ultimately cellular death with increased risks for other neurodegenerative diseases. Thus, neuronal injury represents a wide spectrum of insults impairing brain function and ultimately progressing to forms of advanced aging. Here, we have modeled two common forms of neuronal injury, chemotherapy-induced cognitive impairment (chemobrain) and traumatic brain injury (TBI) in small animals. Within the studies of TBI, we have developed and characterized a novel model of rotational TBI (rTBI), identified Cyclin dependent kinase 5 (Cdk5) as a mediator of rTBI-induced cognitive deficits, and generated a library of aberrant Cdk5 signaling. Within our studies of chemobrain, we have assessed the behavioral, neurophysiological, and neuropathological changes associated with two common, combinatorial chemotherapeutic regimens. Finally, we have conducted single-cell sequencing of chemobrain samples to identify cell-type specific alterations in signal transduction underlying the impairments in mood and cognitive function.
Recommended Citation
Umfress, Alan, "Aberrant Signal Transduction of Neuronal Injury: Trauma and Toxicology" (2023). All ETDs from UAB. 14.
https://digitalcommons.library.uab.edu/etd-collection/14