The DOI matches its Crossref record; 143 of the 166 references it cites were found in a registry or an index.
A Porcine Model of Traumatic Brain Injury via Head Rotational Acceleration
Open accessAbstract
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.
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“Indeed, the complex neuroanatomy and neurophysiology of the human brain, such as cortical folding, substantial white matter, and specific pathophysiology compared to the rodent brain, may facilitate distinct post-injury neuropathology (137).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [137]
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Citations
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Cited by
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Items 101–138 of 138
Chen, Y.-F. J., Herrold, A. A., Walter, A., Reilly, J. L., Seidenberg, P., Nauman, E., Talavage, T., Vandenbergh, D., Slobounov, S., & Breiter, H. (2021) · Journal of Neurotrauma · doi:10.1089/neu.2020.7016 · Cited by 3
“In 67–71 The current work suggests that genetics plays a role in both baseline and long-term interactions between the neurovascular system and behavior in response to HAEs.”
Dan, X.-Z., Wang, Y.-H., Bao, S.-Y., Li, J.-R., Hu, Y., & Yang, L.-X. (2018) · Optical Engineering: The Journal of SPIE · doi:10.1117/1.oe.57.7.074102 · Cited by 3
Modeling Traumatic Brain Injury In Vitro
Bonder, D. E., Keating, C. E., Chandra, N., Cullen, D. K., & Pfister, B. J. (2018) · doi:10.1007/978-1-4939-8564-7_3 · Cited by 3
Self-citationMayer, A. R., Wick, T. V., Miller, S., Connors, K. E., Kumar, D. S., Meier, T. B., van der Horn, H. J., Nathaniel, U., Ling, J. M., Mehos, C. J., et al. (2026) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x261432754 · Cited by 1
“12,22 In Experiment 1, we predicted a dose-dependent relationship between protein efflux and injury severity (i.e. surface area of barrier disruption) that would be partially dependent on molecular weight (UCH-L1 → GFAP → NfL) due to blood-brain barrier (BBB) involvement.”
InfluentialSong, J. Y., Fleysher, R., Ye, K., Kim, M., Ortega, J., Zimmerman, M. E., Lipton, R., & Lipton, M. L. (2026) · Scientific Reports · doi:10.1038/s41598-025-34355-y · Cited by 2
“Prior neuroimaging studies of these disorders have largely reported qualitative features of the GWI 2,4–6 .”
Dietvorst, S., Vervekken, A., & Depreitere, B. (2023) · Brain and Spine · doi:10.1016/j.bas.2023.102728 · Cited by 2
“Based on this animal ’ s characteristics, we made an extrapolation of rotational velocity and acceleration used in the HYGE experiments reported by Cullen et al. (2016) to calculate the rotational acceleration and velocity input required to provoke raised ICP in our animal model (Cullen et al.,…”
BackgroundMethodResultInfluentialGrovola, M. R., Paleologos, N., Brown, D. P., Tran, N., Wofford, K. L., Harris, J., Browne, K., Wolf, J., Cullen, D. K., & Duda, J. (2020) · bioRxiv · doi:10.1101/2020.10.16.343103 · Cited by 2
“In order to attain closed-head diffuse mild TBI in animals, we used a previously described model of head rotational-acceleration in pigs (7,42).”
MethodSelf-citationMagarey, C. C., Quarrington, R., Cripton, P., & Jones, C. F. (2026) · International Journal of Impact Engineering · doi:10.1016/j.ijimpeng.2026.105753 · Cited by 1
Wang, Z., Yuan, W., Li, J., & Qin, M. (2026) · Pharmaceutics · doi:10.3390/pharmaceutics18040477 · Cited by 1
“A critical direction for de-risking clinical translation is the development and adoption of more sophisticated, multi-dimensional TBI models that can more accurately predict therapeutic efficacy in humans [164,168].”
Hirad, A. A., Mix, D., Venkataraman, A., Meyers, S. P., & Mahon, B. Z. (2026) · NeuroImage Clinical · doi:10.1016/j.nicl.2026.103974 · Cited by 2
“…et al., 2023; Ghajari et al., 2017; Hajiaghamemar and Margulies, 2021; Johnson et al., 2013; Arbogast and Margulies, 1998; Corsellis et al., 1973; Cullen et al., 2016; Gennarelli et al., 1982; Graham et al., 1995; Grossman et al., 2012; Omalu et al., 2011; Ommaya, 1995; Palacios et al., 2020).”
Shin, S. S., Browne, K. D., Viaene, A. N., Keim, G. P., Han, D. J., Degani, R. E., Mazandi, V. M., Morton, S., Starr, J. P., Weeks, K., et al. (2025) · Journal of Neurotrauma · doi:10.1177/08977151251401236 · Cited by 1
Self-citationLimitations of Rotational Acceleration for Predicting Concussion: A New Injury Risk Function
Towns, J. A., Cecchi, N. J., Hickey, J. W., O'Brien, W., Roberts, S., Grant, G. A., Zeineh, M., McDonald, S. J., & Camarillo, D. B. (2025) · doi:10.48550/arxiv.2507.09098 · Cited by 1
“17 Finite element modelling of the porcine brain has since shown that rotational acceleration induces diffuse strain in the deep white matter, 18 a region heavily implicated pathologically.”
Abdou, H., Treffalls, R. N., Jodłowski, G., Elansary, N. N., Ptak, T., Walker, P. F., & Morrison, J. J. (2025) · European Journal of Trauma and Emergency Surgery · doi:10.1007/s00068-025-02819-5 · Cited by 1
“The CBV of pigs is also known to be similar to that of humans with reported values in the 3.3 to 4.8 mL/100 g range [13], which also compares favorably with the results of the current study.”
InfluentialO'Donnell, J. C. (2024) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.14541 · Cited by 1
“7 Furthermore, anything less than 60 min of unconsciousness is mild TBI (not associated with DoC), and a few minutes of vestibular disorientation after impact/deep anesthesia (as reported in this study) is of little relevance.”
BackgroundWofford, K. L., Grovola, M. R., Adewole, D. O., Browne, K. D., Putt, M. E., O’Donnell, J. C., & Cullen, D. K. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.09.430268 · Cited by 2
“Furthermore, previous literature found that this injury model can simultaneously generate pathological and functional alterations that are observed in clinical TBI (Smith et al., 1999, 2000; Browne et al., 2011; Cullen et al., 2016; Wofford et al., 2017, 2019; Wolf et al., 2017; Johnson et al., 2018).”
BackgroundMethodInfluentialSelf-citationDevelopment of In Vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury
Brody, D., & Diamond, M. I. (2014) · doi:10.21236/ada596727 · Cited by 1
Rat Models of Central Nervous System Injury
Philips, B. H., Browne, K. D., Cullen, D. K., & Jaber, S. M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-814338-4.00029-5 · Cited by 1
Self-citationBiomechanism of Traumatic Brain Injury Induced by Acceleration Based on Animal Models
Liang, X.-Y., Liu, W.-D., Liu, Z.-X., Wang, L.-Z., & Fan, Y.-B. (2026) · Medicine in Novel Technology and Devices · doi:10.1016/j.medntd.2026.100467
Assessing Motion Fidelity During Closed-Head Rotational Acceleration Traumatic Brain Injury in Pigs
Shin, S., Browne, K., Amador, O., Patton, D., Rosalino, M., Wolf, J. A., Arbogast, K., Meaney, D. F., Cullen, D. K., & Wofford, K. L. (2026) · Research Square · doi:10.21203/rs.3.rs-10806947/v2
“At these injury levels, our group and others have reported damaged white matter, permeabilized neuronal membranes, reactive immune cells, leaky blood brain barrier, altered hippocampal physiology, and perturbed systemic physiology [10, 14, 17, 47, 63, 79].”
InfluentialSelf-citationKao, S.-H., Singh, L. N., Chawla, S., Gaudio, H. A., Browne, K., Shin, S. S., Hobson, L. J., Kenna, S., Starr, J. P., Weeks, M., et al. (2026) · Acta Neuropathologica Communications · doi:10.1186/s40478-026-02384-x
Self-citationSmith, C. J., Hamimi, S., Castellanos, M., Noel, E., Serrano, A. P., Inaltekin, S., Shah, N., Pérez, W., Rauscher, F., Kim, J., et al. (2026) · bioRxiv · doi:10.64898/2026.07.20.739683
“26,44 One potential next step could be the creation of a porcine TBI model based on organoid transplantation.”
Mechanical deformation explains distinct neuroimaging patterns and etiologies in brain trauma
Huang, Y., Zhu, T., Ahmed, I., LaBalle, M., Zhao, Q., Taber, M. F., Sneed, S. E., Kaiser, E. E., West, F. D., Browne, K., et al. (2026) · NeuroImage · doi:10.1016/j.neuroimage.2026.122088
“This interpretation is consistent with the known gross pathology of sagittal-plane head rotation, which frequently produces subdural hemorrhage and extensive blood accumulation at the base of the brain and brainstem (Cullen et al., 2016).”
InfluentialSelf-citationPIGMENT: A deep learning framework for Porcine Immunohistochemistry seGMENTation
Ambastha, P., Dadashkarimi, J., Annavazala, S. K. C., Parker, D., Diaz-Arrastia, R., Song, H.-L., Donahue, R. P., Smith, D. H., Dollé, J.-P., Johnson, V. E., et al. (2026) · bioRxiv · doi:10.64898/2026.06.18.733245
“Standard staining protocol was followed, as previously described [20].”
Self-citationMetformin Modulates Systemic Lipid Remodeling after Traumatic Brain InjuryPreprint
Gusdon, A. M., Cho, S.-M., Chen, H., Radmanesh, F., Ren, X., Dash, P., Choi, J., & Paredes, R. M. (2026) · Research Square · doi:10.21203/rs.3.rs-9583079/v1
“Importantly, the gyrencephalic organization and high white-matter–to– gray-matter ratio of the porcine brain more closely reflect human neuroanatomy than lissencephalic rodent models, strengthening its translational relevance for TBI-related metabolic studies [18, 19].”
Wofford, K. L., Purvis, E. M., Acero, V. P., Gao, J., Rivellini, O. M., Kuo, E., Mietus, C. J., Browne, K. D., O’Donnell, J. C., & Cullen, D. K. (2026) · Acta Neuropathologica Communications · doi:10.1186/s40478-026-02309-8
“The device induced rapid rotational acceleration of the subject’s head, scaled up to induce biomechanical parameters consistent with human TBIs [14, 18].”
InfluentialSelf-citationInvestigating woodpecker drumming using the center of percussion
Koczur, E. M., Parkinson, B., Frecker, M., & Greenwood, T. E. (2026) · Bioinspiration & Biomimetics · doi:10.1088/1748-3190/ae4f47
“Indeed, research on traumatic brain injury recognizes the neck as a critical structure for its influence on rotational acceleration [44, 45], loading [46], and stiffness modulation in both humans [47] and woodpeckers [48].”
PIGSKIN: PIG SKull stripping with synthetic Images and Neural networks
Dadashkarimi, J., Parker, D., Lomer, N. B., Diaz-Arrastia, R., Smith, D. H., Johnson, V. E., Wolf, J. A., & Verma, R. (2026) · AI in neuroscience · doi:10.1177/2997979x261429297
“22,23 Broader validation across breeds, injury types, and sites will be essential.”
Self-citationAderibigbe, O., Wood, L. B., & Margulies, S. S. (2026) · Acta Neuropathologica Communications · doi:10.1186/s40478-026-02260-8
“Animal snouts were then secured on a padded snout clamp and sagittal RNR injuries were delivered using a pneumatic HYGE device (HYGE, Inc., Kittanning, PA, USA) [41].”
Self-citationTBI-induced vessel softening increases brain susceptibility to injury with repeated head trauma
Shojaeianforoud, F., Venezie, A. M., Rubio, J. E., Jaques Reifman, A., Coats, B., & Monson, K. L. (2025) · Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials · doi:10.1016/j.jmbbm.2025.107287
Luo, Q., Nie, R., Du, Z.-W., Xiong, T., Du, X., Yang, L., Li, K., Liu, S.-X., & Duan, A.-W. (2025) · Theoretical and Applied Mechanics Letters · doi:10.1016/j.taml.2025.100601
Evidence of Gait Impairment After mTBI in an Adolescent Pig Model
Vizzeswarapu, N., Kanat, S., Bush, T., & Pelled, G. (2025) · bioRxiv · doi:10.1101/2025.03.31.646330
Oeur, A., Torp, W., & Margulies, S. S. (2024) · Biomedicines · doi:10.3390/biomedicines12112460
“The HYGE device translates linear motion of a pneumatic actuator, via a linkage and bite plate, into a controlled rapid angular rotation of the head [25].”
Self-citationNeuropathological mRNA Expression Changes after Single Mild Traumatic Brain Injury in Pigs
Grovola, M. R., & Cullen, D. K. (2024) · Biomedicines · doi:10.3390/biomedicines12092019
“In order to attain closed-head diffuse mild TBI in animals, we used a previously described model of head rotational acceleration in pigs (for thorough details of our injury model, see [7,23]).”
BackgroundMethodSelf-citationDeveloping an Ovine Model of Impact Traumatic Brain Injury
Magarey, C. C., Quarrington, R., & Jones, C. F. (2023) · SAE International Journal of Transportation Safety · doi:10.4271/09-11-02-0016
Liu, X., Lu, L.-H., Bian, K.-W., Brown, A., & Mao, H.-J. (2021) · Research Square · doi:10.21203/rs.3.rs-271852/v1
“In addition, several rotational injury devices have been developed to induce mTBI in brain by exerting rotation (54-56).”
BackgroundBashir, A. (2019) · doi:10.14288/1.0387516
“4 Inertial loading Inertial loading models have been developed to accelerate the head in the absence of a skull impact in order to isolate the injury components caused by brain motion relative to the skull from those caused by deformations of the skull (Cullen et al., 2016; Johnson et al., 2018).”
BackgroundInfluentialRobinson, M. A., Jaber, S. M., Piotrowski, S. L., & Gomez, T. H. (2018) · Neuromethods · doi:10.1007/978-1-4939-8564-7_10
TITLE : Development of in vivo Biomarkers for Progressive Tau Pathology after Traumatic Brain Injury
Diamond, M. I., & Brody, D. (2014) · doi:10.21236/ada614235
Metadata
- Authors
- Cullen, D. K., Harris, J. P., Browne, K. D., Wolf, J. A., Duda, J. E., Meaney, D. F., Margulies, S. S., & Smith, D. H.
- Affiliations
- Philadelphia VA Medical Center (US)
- University of Pennsylvania (US)
- Corresponding author
- Cullen, D. Kacy
- ORCID
- Venue
- Methods in Molecular Biology
- Publisher
- Springer New York
- Published
- 2016
- Volume
- 1462
- Pages
- 289-324
- ISSN
- 1064-3745 (ISSN-L)
- 1940-6029
- PMC
- PMC5553045
- OpenAlex
- W2514627507
- Cited by
- 142
- References
- 166
- Citations by year
- 2026: 17 · 2025: 15 · 2024: 15 · 2023: 18 · 2022: 18 · 2021: 11 · 2020: 13 · 2019: 16 · 2018: 11 · 2017: 8
- FWCI
- 72.55
- Type
- book chapter
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Methods in molecular biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs (IK2 RX001479, I01-RX001097)
- National Institute of Neurological Disorders and Stroke (R01NS038104, R01NS092398, R01NS088176, R01NS050598, R01NS101108, T32NS043126)
- National Institute of Biomedical Imaging and Bioengineering (R01EB021293)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Automotive and Human Injury Biomechanics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Keywords
- traumatic brain injury, porcine model, angular acceleration, head rotation, brain deformation, injury biomechanics, concussion, linear actuator, neuropathology
- MeSH terms
- Acceleration, Brain Injuries, Traumatic, Animals, Biomechanical Phenomena, Biopsy, Disease Models, Animal, Humans, Immunohistochemistry, Rotation, Swine, Neuroimaging
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