Kinematic Correlates to Behavioral Outcomes and Effects of Caloric Inadequacy in Traumatic Brain Injury in Rats

Traumatic brain injury (traumatic brain injury (TBI)) accounted for 2.88 million Emergency Department Visits Hospitalizations and Deaths (EDHDs) in the USA alone in 2014,not accounting for the many sub-clinical injuries that are often unreported and untreated. A vast majority of these injuries are closed head TBI involving direct contact with the skull and rapid acceleration / deceleration events. While a variety of experimental TBI models exist, most succeed at either reproducing specific mechanisms of injury or specific gross and molecular consequences (diffuse axonal injury, reactive astrocytosis, etc), but not always both. In this work, I highlight a free rotation closed-head traumatic brain injury (FRCHTBI) model that mimics the mechanisms of impact most common in human injuries. Even in high risk scenarios, kinematic information from instrumented equipment or video analysis is typically the best case scenario for quantifying the impact event. As such, I highlight a method for measuring kinematic properties (linear and angular accelerations of the head) in this model using only a high speed camera, as well as an example of behavior analysis taking into account sources of variation common in these models (Chapter 2). Detection of acute, sub-acute, and chronic deficits are crucial to tying behaviorally measured affects of TBI models to their anatomical and molecular consequences, and evaluate efficacy of interventions. In chapter 3, I present a pair of rodent behavioral assays with low barriers to implementation and high clinical significance. The light aversion assay (LAV) is an adaptable measure of photosensitivity, a commonly reported symptom in mild to severe TBI, that can be optimized to detect various severities, and was able to detect differences in very mild TBI 14 days after injury. Gait analysis using open source software and walkway plans was also effective at detecting changes in temporal (stance and swing phase) and spatial (step length) gait parameters 30 min post impact. Lack of appetite is commonly reported following mild to severe TBI, and patients in the neuro intensive care unit (ICU) have been shown to be in highly catabolic states under the current standard of care, indicating inadequate caloric support to repair the injured brain. Despite its involvement across all severities of injury, few studies focus on nutritional interventions following TBI. In chapter 4 I explore a rat TBI adequacy-inadequacy model with and without sodium lactate (NaLac) supplementation as a potential means of exploring the interplay between caloric sufficiency and lactate supplementation. However, with the impact parameters used in the present study a very mild TBI was induced, below the detection threshold of several commonly used tests. This unfortunately was not a sufficient level of injury to evaluate group differences for the nutritional model introduced. Collectively, this work explores clinically relevant methods related to many stages of rodent TBI studies including injury induction (chapter 2), severity detection and outcome evaluation (chapter 3), and experimental nutritional interventions (chapter 4).

Advisor: Brooks, George A