A Porcine Model of Traumatic Brain Injury via Head Rotational Acceleration.
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.
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. dkacy@mail.med.upenn.edu.|Department of Neurology, Perelman School of Medicine, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA. dkacy@mail.med.upenn.edu.|Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. dkacy@mail.med.upenn.edu.
D Kacy
DK
Cullen
Department of Neurology, Perelman School of Medicine, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA.|Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105 Hayden Hall/3320 Smith Walk, Philadelphia, PA, USA.
James P
JP
Harris
Department of Neurology, Perelman School of Medicine, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA.|Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105 Hayden Hall/3320 Smith Walk, Philadelphia, PA, USA.
Kevin D
KD
Browne
Department of Neurology, Perelman School of Medicine, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA.|Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 371 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA, USA.
John A
JA
Wolf
Department of Neurology, Perelman School of Medicine, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA.
John E
JE
Duda
Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105C Hayden Hall/3320 Smith Walk, Philadelphia, PA, USA.
David F
DF
Meaney
Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.|Center for Brain Injury & Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, 105D Hayden Hall/3320 Smith Walk, Philadelphia, PA, USA.
Susan S
SS
Margulies
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.
Douglas H
DH
Smith
D000054:Acceleration; D000818:Animals; D001696:Biomechanical Phenomena; D001706:Biopsy; D000070642:Brain Injuries, Traumatic / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D059906:Neuroimaging; D012399:Rotation; D013552:Swine
Axonal injury; Biomechanics; Concussion; Degeneration; Diffuse brain injury (DBI); Modeling; Neuropathology; Traumatic brain injury (TBI)