PATHOPHYSIOLOGICAL CHANGES WITHIN THE CENTRAL AUDITORY SYSTEM FOLLOWING MILD TRAUMATIC BRAIN INJURY
Creators: name: Fernandez, Joseph Mario
Publisher: name: Purdue University Graduate School
Year: 2022
Subjects: Biomedical engineering not elsewhere classified
Central nervous system

description: Traumatic Brain Injury (TBI) is one of the most prevalent causes of injury in young adults, and is a leading cause of hospitalization, disability, and even death. Although severe TBI can lead to serious acute injury (such as brain hemorrhaging and skull fractures) and chronic disability, the vast majority (~80%) of TBIs are mild in nature, and do not present with such drastic symptoms. As such, these mild TBIs may go undiagnosed or underreported. Without overt, acute symptoms, mild TBIs may be particularly insidious as they are shown to correlate with increased risk of chronic social and cognitive processing impairments, as well as the risk of developing neurodegenerative diseases later in life. Additionally, many people who suffer TBIs, whether on the sports field, field of battle, or even in everyday life, often are at increased risk of additional TBIs, which likely increase the risk of life-long post injury complications. Given these risk factors, there is a clear need to understand how mild TBIs affect the brain both acutely and chronically and develop tactics to properly diagnose and treat mild injuries early. In this dissertation, we argue for the potential use of Auditory Evoked Potentials (AEPs), a clinically used noninvasive set of tests, as an effective route for improved diagnostics of mild TBIs. To achieve this, we must first understand the relationship between underlying anatomical changes and chronic deficits in mild injury. In blast induced TBIs, some of the most common sequalae, both acutely and chronically, are auditory in nature. Temporary changes in hearing thresholds or tinnitus are very common, but chronic impairments in more complex auditory processing tasks, such as hearing speech-in-noise, are often reported as well. Although acute changes are likely due to damage to the peripheral auditory system, there is mounting evidence suggesting damage to central auditory regions may play a clear role in chronic processing changes, however, this is still poorly understood. Recent studies of concussions in sports medicine have found that impact induced TBIs may produce long-term, but not acute, deficits in subtle auditory processing function as well. Given its potential for ubiquitous damage following TBIs of multiple forms, understanding the post-injury central auditory system can act as a window into the time-course and severity of secondary biochemical changes and chronic processing issues seen following mild TBI. Here we use a well-established rat blast TBI model to examine the acute and chronic time course of auditory processing changes, as well as biochemical and anatomical changes. We show a clear biphasic response of acute and chronic changes in auditory processing. Changes in oxidative stress, inflammation, and inhibition/excitation show similar patterns within key regions of the central auditory system (CAS), suggesting a link between AEP results and underlying chronic damage. Our second objective was to design a more clinically relevant and consistent animal model of free-range of motion impact induced TBI. Once developed, we examined similar AEP and immunohistochemical tests to determine the degree of similarity of CAS changes in a second form of TBI. Interesting, while AEP results suggest some long-term changes in auditory processing, these were not identical to blast changes. Finally, we utilized a computational model for axonal node damage to assess one method of potential damage resulting from the oxidative stress changes post injury and provides a framework for future modeling techniques for improved diagnosis and treatment. These results together suggest that AEPs have the potential to improve diagnostics and monitoring tools in mild TBIs, regardless of injury type.