Citation

Cullen DK, Harris JP, Browne KD, Wolf JA, Duda JE, Meaney DF, Margulies SS, Smith DH. Methods Mol. Biol. 2016; 1462: 289-324.

Affiliation

Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105E Hayden Hall/3320 Smith Walk, Philadelphia, PA, 19104, USA.

Copyright

(Copyright © 2016, Holtzbrinck Springer Nature Publishing Group)

DOI

10.1007/978-1-4939-3816-2_17

PMID

27604725

Abstract

Unique from other brain disorders, traumatic brain injury (TBI) generally results from a discrete biomechanical event that induces rapid head movement. The large size and high organization of the human brain makes it particularly vulnerable to traumatic injury from rotational accelerations that can cause dynamic deformation of the brain tissue. Therefore, replicating the injury biomechanics of human TBI in animal models presents a substantial challenge, particularly with regard to addressing brain size and injury parameters. Here we present the historical development and use of a porcine model of head rotational acceleration. By scaling up the rotational forces to account for difference in brain mass between swine and humans, this model has been shown to produce the same tissue deformations and identical neuropathologies found in human TBI. The parameters of scaled rapid angular accelerations applied for the model reproduce inertial forces generated when the human head suddenly accelerates or decelerates in falls, collisions, or blunt impacts. The model uses custom-built linkage assemblies and a powerful linear actuator designed to produce purely impulsive non-impact head rotation in different angular planes at controlled rotational acceleration levels. Through a range of head rotational kinematics, this model can produce functional and neuropathological changes across the spectrum from concussion to severe TBI. Notably, however, the model is very difficult to employ, requiring a highly skilled team for medical management, biomechanics, neurological recovery, and specialized outcome measures including neuromonitoring, neurophysiology, neuroimaging, and neuropathology. Nonetheless, while challenging, this clinically relevant model has proven valuable for identifying mechanisms of acute and progressive neuropathologies as well as for the evaluation of noninvasive diagnostic techniques and potential neuroprotective treatments following TBI.

Language: en