Direction-dependent Responses to Traumatic Brain Injury in Pediatric Pigs

Traumatic brain injury (TBI) in children is a costly and alarmingly prevalent public health concern. Children (4–11 years of age) in the US have the highest rate of TBI-related emergency department visits. The plane of head rotation significantly affects neurocognitive deficits and pathophysiological responses such as axonal injury, but is largely ignored in TBI literature. In Chapter 1, an outline of existing research is provided, including the lack of attention to diagnosis, treatment, and prevention in children, who exhibit distinct biomechanical and neuropathological responses to TBI. Additionally, we hypothesize that the plane of head rotation in TBI induces a) region-specific changes in axonal injury, which lead to acute and chronic changes in electrophysiological responses; b) changes to event-related potentials and resting state electroencephalography (EEG) and c) tract-oriented strain and strain rate alterations in the white matter. All work in this dissertation is based on a well-established piglet model of TBI. In Chapter 2, we assess a novel rotational head kinematic metric, rotational work (RotWork), which incorporates head rotation rate, direction, and brain shape, as a predictor of acute axonal injury. This metric provides an improvement over existing metrics and could be useful in the development of effective child safety equipment used in recreation or transportation. In Chapter 3, we generate functional networks from auditory event-related potentials and use the patterns of change to distinguish injured brains from non-injured; the resulting algorithm showed an 82% predictive accuracy. In Chapter 4, we find elevations in network nodal strength, modularity and clustering coefficient after TBI across all frequency bands relative to baseline, whereas both metrics were reduced in shams. We report the first study using resting state EEG to create functional networks in relation to pediatric TBI, noting that this work may assist in the development of TBI biomarkers. In Chapter 5, we use a high-resolution finite element model to examine the effects of head rotation plane on the distribution of regional strains and strain rates. Sagittal rapid head rotations induced significantly larger volume fraction of damaged brainstem than axial and coronal rotations. We also found that local tissue deformation and histopathology were head direction- and region-dependent but poorly correlated at a local scale. Finally, in Chapter 6, we conclude that the work presented in this dissertation is novel and contributes valuable knowledge to the study of pediatric TBI, and that consideration of the plane of head rotation is critical to the understanding and accurate prediction of pediatric functional and region-dependent responses to TBI