PT  - JOURNAL ARTICLE
AU  - Joshua A. Beitchman
AU  - Jonathan Lifshitz
AU  - Neil G. Harris
AU  - Theresa C. Thomas
AU  - Audrey D. Lafrenaye
AU  - Anders Hånell
AU  - C. Edward Dixon
AU  - John T. Povlishock
AU  - Rachel K. Rowe
TI  - Spatial distribution of neuropathology and neuroinflammation elucidate the biomechanics of fluid percussion injury
AID  - 10.1101/2020.10.05.325514
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.10.05.325514
4099  - http://biorxiv.org/content/early/2020/10/07/2020.10.05.325514.short
4100  - http://biorxiv.org/content/early/2020/10/07/2020.10.05.325514.full
AB  - Diffuse brain injury is better described as multi-focal, where pathology can be found adjacent to seemingly uninjured neural tissue. In experimental diffuse brain injury, pathology and pathophysiology have been reported far more lateral than predicted by the impact site. Finite element biomechanical models of diffuse brain injury predict regions of maximum stress and strain. However, the application of a skull with uniform thickness may mask the pathophysiology due to varying thickness of human and animal skulls. Force applied to the intact skull would diffuse the forces, whereas forces applied through an open skull are distributed along paths of least resistance within and then exiting the skull. We hypothesized that the local thickening of the rodent skull at the temporal ridges serves to focus the intracranial mechanical forces experienced during brain injury and generate predictable pathology in underlying cortical tissue. We demonstrated local thickening of the skull at the temporal ridges using contour analysis of coronal skull sections and oblique sectioning on MRI. After diffuse brain injury induced by midline fluid percussion injury (mFPI), pathological foci along the anterior-posterior length of cortex under the temporal ridges were evident acutely (1, 2, 7 days) and chronically (28 days) post-injury by deposition of argyophilic reaction product. Area CA3 of the hippocampus and lateral nuclei of the thalamus showed pathological change, suggesting that mechanical forces to or from the temporal ridges shear subcortical regions. A proposed model of mFPI biomechanics suggests that injury force vectors reflect off the skull base and radiate toward the temporal ridge due to the material properties of the skull based on thickness, thereby injuring ventral thalamus, dorsolateral hippocampus, and sensorimotor cortex. Surgically thinning the temporal ridge prior to injury reduced the injury-induced inflammation in sensorimotor cortex. These data build evidence for the temporal ridges of the rodent skull to contribute to the observed pathology, whether by focusing extracranial forces to enter the cranium or intracranial forces to escape the cranium. Pre-clinical investigations can take advantage of the predicted pathology to explore injury mechanisms and treatment efficacy.HighlightsThe temporal ridge is 75% thicker than the adjacent skull of the rodentExperimental diffuse TBI neuropathology occurs beneath the length of the temporal ridgeNeuropathology encompasses sensorimotor cortex, somatosensory thalamus, and dorsolateral hippocampusProposed mechanism of biomechanical injury forces include the temporal ridgeCompeting Interest StatementThe authors have declared no competing interest.