Purdue University Graduate School
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posted on 2022-07-28, 19:47 authored by Joseph Mario FernandezJoseph Mario Fernandez

 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.  


Degree Type

  • Doctor of Philosophy


  • Biomedical Engineering

Campus location

  • West Lafayette

Advisor/Supervisor/Committee Chair

Riyi Shi

Additional Committee Member 2

Edward Bartlett

Additional Committee Member 3

Michael Heinz

Additional Committee Member 4

Amy Brewster

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