Document Type


Date of Award

Fall 2017

Degree Name

Doctor of Philosophy in Biomedical Engineering - (Ph.D.)


Biomedical Engineering

First Advisor

Bryan J. Pfister

Second Advisor

N. Chandra

Third Advisor

James Haorah

Fourth Advisor

Vijayalakshmi Santhakumar

Fifth Advisor

Kevin Pang


Repetitive mTBI and concussion are a major risk factor for developing long-term cognitive and behavioral impairments. Curiously, cumulative head injuries sustained over an individuals’ career, involving contact activities (e.g. athletes and military personnel), are beginning to be implicated in long-term consequences, such as dementia. Recently, chronic traumatic encephalopathy (CTE) has gained momentum in the science and medical community as a neurodegenerative disease of repetitive head injuries. CTE was observed at autopsy of former athletes that did not closely correlate with a clinical history of concussion. Thus, suggesting cumulative subconcussive insults may induce long-term damage.

Investigating the etiology of subconcussive and cumulative subconcussive insults clinically is not feasible; however, understanding what correlation exists between cumulative effects of repetitive subconcussive insults is crucial for the medical and scientific community. This study used a lateral fluid percussion injury (lFPI) to model a subconcussive insult; specifically, to test the hypothesis that an initial subconcussive insult will not lead to any significant detectable levels of behavioral or cellular damage, yet cumulative intra-day subconcussive insults will manifest into detectable changes in neuropathology and behavior.

This study developed a novel animal model of subconcussive brain injury (scTBI) paradigm and the effects of cumulative intra-day scTBI utilizing a digitally controlled fluid percussion injury device (dcFPI). Acute behavioral effects of cumulative 5x scTBI resulted in longer duration in latency of righting reflex compared to 5x SHAM group. Neuronal degeneration was assessed at 24 h using Fluoro - Jade C, with sparse neuronal degeneration in the granule cell layer of the hippocampus and all 5x scTBI subjects exhibit hemorrhage. Neurobehavior assessment revealed transient suppression of ASR on PID1, returning to SHAM levels by PID4. The presence of immunoreactive microglia and reactive astrocytes was observed in cumulative 5x scTBI at 24 h and 1 w when compared to 5x SHAM group. These findings indicate one scTBI does not result in acute behavior deficits or neuronal degeneration, however cumulative scTBI results transient brainstem dysfunction, blood brain barrier disruption and prolonged neuroinflammation.



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