Traumatic brain injury is a leading cause of death and disability in infants worldwide. Injury mechanisms include mechanical and biological insults, but few studies have examined the interaction between these mechanisms. We investigated the effect of head rotation direction on inertial brain injury in neonatal piglets using animal experiments and finite element (FE) modeling. We hypothesized that brain asymmetries lead to directiondependent differences in tissue strains, cerebral blood flow (CBF), and histopathological responses to rotational injury. We developed and partially validated a FE model of the piglet brain and skull with an interface representative of meningeal tissues. We developed an efficient histological fluorescent microsphere technique using fluorescent imaging technology and automated analysis software to facilitate measurement of CBF changes.

We observed direction-dependent differences in mechanical, physiological, and histopathological responses to a single sagittal, horizontal, or coronal head rotation. Sagittal rotations produced physiological derangements indicating medullary dysfunction and correspondingly high medullary strains. Sagittal rotations also produced significant regional CBF reductions compared to sham and the highest regional tissue strains. Coronal rotations produced no apparent physiological changes compared to sham and resulted in the lowest tissue strains. Horizontal rotations produced more variable physiological outcomes intermediate between those of sagittal and coronal, as well as intermediate tissue strains. For all injured animals, lower regional CBF correlated with higher tissue strains.

Significant regional axonal injury resulted from sagittal and horizontal but not coronal rotations. Regional axonal injury frequently occurred in the absence of ischemia and correlated with regional tissue strains but not with regional CBF reductions. Tissue infarction was observed in sagittal and horizontal but not coronal animals, was always accompanied by axonal injury, and correlated with regional strains but not with 1 hour post-injury regional CBF reductions. The strain threshold for 50% probability of infarction was twice as high as that for axonal injury, consistent with these observations. We conclude that early axonal injury following trauma is due to mechanical rather than ischemic mechanisms.

Recognizing the effect of head rotation direction on injury outcomes improves our understanding of brain injury mechanisms and leads to the development of better injury prevention and treatment strategies.