Advisory Committee Chair
Candace L Floyd
Advisory Committee Members
Farah D Lubin
Michelle L Olsen
Trent E Tipple
Hubert M Tse
Document Type
Dissertation
Date of Award
2017
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Mild traumatic brain injury (mTBI) is a major health concern and accounts for over 75% of the 2.5 million brain injuries reported annually in the United States. Afflicted individuals typically experience a broad spectrum of physical, cognitive, and neuropsychological symptoms. Repeated mTBIs (rmTBIs) can further exacerbate these physiological alterations and negatively impact patient quality of life. Currently, there are no therapeutic agents that have successfully navigated clinical trials to be shown efficacious despite mounds of preclinical evidence suggesting to the contrary. This lack of translation exposes the dire need to design, characterize, and implement better and more relevant model systems of mTBI and rmTBI. To begin to fill this void, we investigated the spectrum of behavioral alterations induced with an impact-acceleration (IA) model of mTBI and rmTBI consisting of 3 impacts with an inter-injury interval of 24 hours. Consistent with clinical literature, we found that mice receiving rmTBIs exhibited a worse prognosis. We observed rmTBI related sleep disturbances using activity chambers and decreases in species-typical activities. Cognitive impairment following mTBI and rmTBI is a highly investigated area, but there is high variance between studies with traditional assessments. By incorporating reversals within the standard Morris water maze (MWM), we could detect the subtle deficits induced with rmTBIs. In the patient population, however, cognitive ability is often measured with computerized cognitive assessments. To increase clinical relevancy, our second study evaluated mice ability to perform on rodent equivalent versions of computerized cognitive touchscreen assessments. Surprisingly, we found that mTBI did not result in significant deficits in hippocampal dependent tasks. The final study of this dissertation departed from measuring behavioral consequences and aimed to elucidate the acute pathophysiological sequelae of rmTBI. Neuroinflammation is thought to play a key role in the secondary injury mechanisms that underlie functional deficits. Consequently, we investigated various aspects of neuroinflammation and observed modest alterations in glial activation and elevation of inflammatory cytokines. Collectively, this body of work attempts to provide a comprehensive characterization of the myriad functional alterations and acute pathophysiological responses associated with an experimental model of rmTBI.
Recommended Citation
Nichols, Jessica Nicole, "Modeling Mild and Repeated Mild Traumatic Brain Injury Induced Functional and Pathophysiological Alterations" (2017). All ETDs from UAB. 2588.
https://digitalcommons.library.uab.edu/etd-collection/2588