Research Assistant Professor Uniformed Services University Bethesda, Maryland
Abstract Text:
Background: The CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration) is a biomechanically and clinically relevant mTBI (mild Traumatic Brain Injury) model, causing diffuse and persistent axonal injury. The use of rotational acceleration is particularly representative of many injuries that occur via sports, motor vehicle or combat. To study this brain injury model, we used the ferret, whose brain is gyrencephalic, contains a high percentage of white matter, and other morphological features that mimic the human brain. The ferret (having many sulci and gyri) CHIMERA model may more closely mimic the neuropathology observed after human traumatic brain injury, however the extent and distribution of pathology after this injury remains under investigation. In this study we investigated the CHIMERA effects and also compared the resulting pathology with the blast (shockwave) injury. To do this, we studied the expression of several proteins known to be associated with brain injury using western blot in multiple brain regions of control and injured animals.
Methods: We evaluated mild CHIMERA brain injury by varying the impact energy (18-36 Joules) and the use of an interface device that had a linear or rotational alignment. The brains of young adult, male ferrets were assessed with Western blot and/or immunohistochemistry at 1 week, 4 weeks or 12 weeks post injury. We evaluated proteins related to neurodegeneration: tau, pTau (phosphorylated tau), 3R, 4R (isoforms of tau), and prion protein. For comparison, we also evaluated repetitive mild blast brain injury (either 4 blasts in 1 hour or 4 blasts over 4 days at 15-21 PSI).
Results: Pathology is variable across the ferret brain at 1 week following the CHIMERA injury. Wide regions of the frontal cortex consistently show evidence of injury, while in the temporal cortex, the anterior portions (i.e. surrounding/including the hippocampus) are consistently higher in pathology compared with posterior aspects of the temporal cortex. Occipital and parietal cortices generally showed increased pathology. When we used an interface device with the CHIMERA, the parameters leading to the most pathology were 70 PSI in the linear orientation. At this setting, the CHIMERA and the blast (4 blasts in 1 hour) result in similar pathology in the frontal cortex at 4 weeks post injury. Summary: The CHIMERA injury model used in the ferret results in a relatively widespread distribution of injury, but frontal brain areas seem to be especially affected. An interface device used with the CHIMERA appears to be highly useful to permit relatively high impact without causing concomitant injuries. Disclaimer: The views expressed here are those of the authors alone and do not represent those of the USUHS or the US Government. The authors have no conflicts of interest with the work presented here.
