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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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Cites
The Epidemiology and Impact of Traumatic Brain Injury: A Brief Overview
Langlois, J., Rutland-Brown, W., & Wald, M. (2006) · The journal of head trauma rehabilitation · doi:10.1097/00001199-200609000-00001 · Cited by 3,893
National Center for Injury Prevention and Control (U.S.). Division of Injury Response., Faul, M., Wald, M. M., Wu, L., & Coronado, V. G. (2010) · doi:10.15620/cdc.5571 · Cited by 3,494
Langlois, J., Rutland-Brown, W., & Thomas, K. (2006) · PsycEXTRA Dataset · doi:10.1037/e721222007-001 · Cited by 3,003
Mild traumatic brain injury in U.S. soldiers returning from Iraq
Hoge, C. W., McGurk, D., Thomas, J. L., Cox, A. L., Engel, C. C., & Castro, C. A. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa072972 · Cited by 2,775
The impact of traumatic brain injuries: A global perspective
Hyder, A. A., Wunderlich, C. A., Puvanachandra, P., Gururaj, G., & Kobusingye, O. C. (2007) · Neurorehabilitation · doi:10.3233/nre-2007-22502 · Cited by 1,816
Diffuse axonal injury and traumatic coma in the primate
Gennarelli, T. A., Thibault, L. E., Adams, J. H., Graham, D. I., Thompson, C. J., & Marcincin, R. P. (1982) · Annals of Neurology · doi:10.1002/ana.410120611 · Cited by 1,528 · cited 2×
“Moreover, this work revealed patterns of prominent neuropathology including DAI similar to that seen in humans postmortem [75].”
Animal models of traumatic brain injury
Xiong, Y., Mahmood, A., & Chopp, M. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3407 · Cited by 1,456 · cited 1×
“Moreover, the majority of rodent TBI studies utilize open skull techniques and are dominated by focal/ impact injuries, which poorly replicate diffuse brain injury and inherently possess craniectomy and/or bleeding, which confound any attempt at “mild” levels of TBI [93].”
(1999) · doi:10.1097/00001199-199912000-00009 · Cited by 1,387
Axonal pathology in traumatic brain injury
Johnson, V. E., Stewart, W., & Smith, D. H. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2012.01.013 · Cited by 1,273 · cited 2×
“Specifically, many of these proteins are the primary constituents of the pathologic inclusions found in several neurode-generative diseases [19, 31, 142, 145].”
Self-citationDiffuse axonal injury in head injury: definition, diagnosis and grading
Adams, J. H., Doyle, D., Ford, I., Gennarelli, T. A., Graham, D. I., & Mclellan, D. R. (1989) · Histopathology · doi:10.1111/j.1365-2559.1989.tb03040.x · Cited by 1,176
Research works printed but not linked: 17
- Graham R, Rivara FP, Ford MA, Spicer CM (2014) Sports-related concussions in youth: improving the science, changing the culture. The National Academies Press, Washington, DC
- Prevention, C. f. D. C. a., and Control, N. C. f. I. P. a. (2003) Report to congress on mild traumatic brain injury in the United States: steps to prevent a serious public health problem. Centers for Disease Control and Prevention, Atlanta, GA
- Prevention, C. f. D. C. a. (2011) Nonfatal traumatic brain injuries related to sports and recreation activities among persons aged ≤19 Years—United States, 2001–2009. MMWR 60:1337–1342
- McIntosh TK, Smith DH, Meaney DF, Kotapka MJ, Gennarelli TA, Graham DI (1996) Neuropathological sequelae of traumatic brain injury: relationship to neurochemical and biomechanical mechanisms. Lab Invest 74:315–342
- Gennarelli TA (1993) Mechanisms of brain injury. J Emerg Med 11(Suppl 1):5–11
- McIntosh TK, Juhler M, Raghupathi R, Saatman KE, Smith DH (1999) Secondary brain injury: neurochemical and cellular mediators. In: Marion W (ed) Traumatic brain injury. Thieme Medical Publishers, New York, NY, pp 39–54
- McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA (2009) Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 68:709–735 · DOI · Paper page
- McIntosh TK (1994) Neurochemical sequelae of traumatic brain injury: therapeutic implications. Cerebrovasc Brain Metab Rev 6:109–162
- Ryan LM, Warden DL (2003) Post concussion syndrome. Int Rev Psychiatry 15:310–316 · DOI
- Yarnell P, Ommaya AK (1969) Experimental cerebral concussion in the rhesus monkey. Bull N Y Acad Med 45:39–45
- Gennarelli TA, Thibault LE, Ommaya AK (1971) Comparison of linear and rotational acceleration in experimental cerebral concussion. Proceedings of the 15th Stapp car crash conference, New York: society of automotive engineers, pp 797–803
- Kleiven S (2013) Why most traumatic brain injuries are not caused by linear acceleration but skull fractures are. Front Bioeng Biotechnol 1:15 · DOI
- Graham DI, Adams JH, Gennarelli TA (1988) Mechanisms of non-penetrating head injury. Prog Clin Biol Res 234:159–168
- Thibault LE, Gennarelli TA (1989) Biomechanics of diffuse brain injuries. Proceedings of the 10th international technical conference on experimental safety vehicles. DOT, NHTSA
- Wolf JA, Johnson BN, Johnson VE, Browne KD, Mietus CJ, Smith DH, Grady MS, Cohen A, Cullen DK (in review) Concussion induces hippocampal circuitry disruption in swine
- Wolf JA, Ulyanova AV, Browne KD, Koch P, Grovola MR, Johnson VE, Cullen DK (2014) Hippocampal network disruptions after diffuse brain injury in swine. Winter conference on brain research
- Gennarelli TA, Pintar FA, Yoganandan N (2003) Biomechanical tolerances for diffuse brain injury and a hypothesis for genotypic variability in response to trauma. Annu Proc Assoc Adv Automot Med 47:624–628
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Johnson, V. E., Weber, M. T., Xiao, R., Cullen, D. K., Meaney, D. F., Stewart, W. B., Jr., & Smith, D. H. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1824-0 · Cited by 163
“The parameters are based on Holbourn’s Scaling Equation [63], where the interaction of brain mass with the level of head rotational acceleration is taken into account [19, 39].”
MethodSelf-citationLarge animal models of traumatic brain injury
Vink, R. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24079 · Cited by 150
“With these technical adjustments, the pig inertial acceleration model has been able to produce graded neuropathological and functional changes that are correlated to the severity of injury (Cullen et al., 2016).”
MethodThe Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease
Kokiko-Cochran, O. N., & Godbout, J. P. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00672 · Cited by 128
“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).”
BackgroundLarge animal models of stroke and traumatic brain injury as translational tools
Sorby‐Adams, A., Vink, R., & Turner, R. J. (2018) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00163.2017 · Cited by 108
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“These characteristics allow for pathology to develop in patterns and extents seen in humans (Cullen et al., 2016; McKee et al., 2009; Meaney et al., 1995).”
BackgroundSelf-citationAcute drivers of neuroinflammation in traumatic brain injury
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“Importantly, this animal model generates pathology mimetic of clinical TBI and could be utilized to better investigate drivers of acute and chronic neuroinflammation that are translationally relevant to clinical presentations (Cullen et al., 2016).”
Self-citationZhan, X.-H., Zhou, Z., Liu, Y.-Z., Cecchi, N. J., Hajiahamemar, M., Zeineh, M., Grant, G. A., & Camarillo, D. B. (2024) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2024.112456 · Cited by 91
Namjoshi, D., Cheng, W.-H., Bashir, A., Wilkinson, A., Stukas, S., Martens, K. M., Whyte, T., Abebe, Z. A., McInnes, K. A., Cripton, P., et al. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.03.003 · Cited by 90
Evaluation of Tissue-Level Brain Injury Metrics Using Species-Specific Simulations
Wu, T., Hajiaghamemar, M., Giudice, J. S., Alshareef, A., Margulies, S., & Panzer, M. (2021) · Journal of Neurotrauma · doi:10.1089/neu.2020.7445 · Cited by 75
“On the other hand, non-rodent in vivo TBI models 23–26 provides accessibility to pathophysiological mechanisms and can be tested for a broader range of injury severities at well-control and characterized loading conditions.”
Self-citationFesharaki‐Zadeh, A., & Datta, D. (2024) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2024.1371213 · Cited by 83
Wofford, K. L., Harris, J. P., Browne, K. D., Brown, D. P., Grovola, M. R., Mietus, C. J., Wolf, J. A., Duda, J. E., Putt, M. E., Spiller, K. L., et al. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.01.004 · Cited by 66
“However, head rotation at these levels of angular velocity/ acceleration in the sagittal plane induced prolonged loss of consciousness and often significant hematoma (Cullen et al., 2016).”
BackgroundMethodInfluentialSelf-citationClinical Relevance of Behavior Testing in Animal Models of Traumatic Brain Injury
Shultz, S. R., McDonald, S. J., Corrigan, F., Semple, B. D., Salberg, S., Zamani, A., Jones, N. C., & Mychasiuk, R. (2019) · Journal of Neurotrauma · doi:10.1089/neu.2018.6149 · Cited by 68
The Use of Pigs as a Translational Model for Studying Neurodegenerative Diseases
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McNamara, E. H., Grillakis, A., Tucker, L. B., & McCabe, J. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113409 · Cited by 61
“Consistently, greater damage is sustained in tracts lying in the plane of rotation, and coronal rotation in the primate may essentially match horizontal plane effects in the pig as a result of cephalic flexure in primates (Cullen et al., 2016; Eucker et al., 2011).”
InfluentialConcussion Induces Hippocampal Circuitry Disruption in Swine
Wolf, J. A., Johnson, B. N., Johnson, V. E., Putt, M., Browne, K. D., Mietus, C. J., Brown, D. P., Wofford, K. L., Smith, D. H., Grady, M. S., et al. (2017) · Journal of Neurotrauma · doi:10.1089/neu.2016.4848 · Cited by 61
Self-citationWu, T., Antona-Makoshi, J., Alshareef, A., Giudice, J. S., & Panzer, M. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2019.6576 · Cited by 48
Animal models of closed-skull, repetitive mild traumatic brain injury
Hoogenboom, W. S., Branch, C. A., & Lipton, M. L. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.02.016 · Cited by 59
The Immune System's Role in the Consequences of Mild Traumatic Brain Injury (Concussion)
Verboon, L. N., Patel, H. C., & Greenhalgh, A. D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.620698 · Cited by 63
“In a pig model of closed-head rotational acceleration, biomechanical loading parameters can be replicated that are thought to underlie neuropathology of mild TBI in humans (157).”
BackgroundThe Pig as a Translational Animal Model for Biobehavioral and Neurotrauma Research
Netzley, A. H., & Pelled, G. (2023) · Biomedicines · doi:10.3390/biomedicines11082165 · Cited by 42
“The procedure typically involves a specialized device that allows controlled rotational movement [69].”
BackgroundLarge animal models of traumatic brain injury
Dai, J., Ma, Y.-B., Le, N., Cao, J., & Wang, Y. (2018) · International Journal of Neuroscience · doi:10.1080/00207454.2017.1380008 · Cited by 42
Roadmap for Advancing Pre-Clinical Science in Traumatic Brain Injury
Smith, D. H., Kochanek, P. M., Rosi, S., Meyer, R., Ferland‐Beckham, C., Prager, E. M., Ahlers, S. T., & Crawford, F. (2021) · Journal of Neurotrauma · doi:10.1089/neu.2021.0094 · Cited by 46
Self-citationHajiaghamemar, M., Seidi, M., Oeur, A., & Margulies, S. S. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.04.019 · Cited by 37
“Large animal models better resemble the biomechanics of brain tissue injury because the gross neuroanatomy and relative composition of white and grey matter tissues are similar between the human and pig brain (Cullen et al., 2016).”
Self-citationBurrell, J., Browne, K., Dutton, J., Das, S., Brown, D. P., Laimo, F. A., Roberts, S. E., Petrov, D., Ali, Z. S., Ledebur, H., et al. (2019) · bioRxiv · doi:10.1101/610147 · Cited by 36
Self-citationConcussion leads to widespread axonal sodium channel loss and disruption of the node of Ranvier
Song, H., McEwan, P. P., Ameen‐Ali, K. E., Tomasevich, A., Dietrich, C. K., Palma, A., Arroyo, E. J., Dollé, J.-P., Johnson, V. E., Stewart, W. B., Jr., et al. (2022) · Acta Neuropathologica · doi:10.1007/s00401-022-02498-1 · Cited by 37
Self-citationElastic behavior of brain simulants in comparison to porcine brain at different loading velocities.
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“Using this large animal model of TBI, researchers have induced reproducible neurological and neuropathological deficits including loss of consciousness, mild edema, increased intracranial pressure, astrogliosis, diffuse axonal injury, and neuroinflammation [56, 57, 102, 103].”
MethodSelf-citationGrovola, M. R., Paleologos, N., Brown, D. P., Tran, N., Wofford, K. L., Harris, J. P., Browne, K. D., Shewokis, P. A., Wolf, J. A., Cullen, D. K., et al. (2021) · Brain Pathology · doi:10.1111/bpa.12953 · Cited by 26
“In order to attain closed- head diffuse mild TBI in animals, we used a previously described model of head rotational acceleration in pigs (26, 27).”
MethodSelf-citationDiffusion Tensor Imaging of the Evolving Response to Mild Traumatic Brain Injury in Rats
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Modulation of Macrophage Phenotype via Phagocytosis of Drug-Loaded Microparticles
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“This immunomodulatory strategy could have therapeutic applications in a multitude of dif fi cult-to-access in fl ammatory pathologies including traumatic brain injury, 47,48 myocardial infarction, 49 or diabetes.”
BackgroundSelf-citationGrovola, M. R., Paleologos, N., Wofford, K. L., Harris, J. P., Browne, K. D., Johnson, V. E., Duda, J. E., Wolf, J. A., & Cullen, D. K. (2020) · Journal of Neuroinflammation · doi:10.1186/s12974-020-1720-0 · Cited by 24
Self-citationConverging early responses to brain injury pave the road to epileptogenesis
Neuberger, E. J., Gupta, A. K., Subramanian, D., Korgaonkar, A. A., & Santhakumar, V. (2017) · Journal of Neuroscience Research · doi:10.1002/jnr.24202 · Cited by 20
“Other methods employed to mimic traumatic brain injury include, weight drop models of impact injury, primary blast wave TBI, rotational TBI, and denervation injury from cortical undercut (Adelson, Dixon, Robichaud, & Kochanek, 1997; Cullen et al., 2016; Prince et al., 2009; Sundaramurthy et al., 2012).”
MethodMayer, A. R., Dodd, A. B., Ling, J. M., Stephenson, D. D., Rannou-Latella, J. G., Vermillion, M. S., Mehos, C. J., Johnson, V. E., Gigliotti, A. P., Dodd, R. J., et al. (2020) · Shock · doi:10.1097/shk.0000000000001653 · Cited by 26
“A closed-head TBI (28) was initiated via a pneumatic device (HYGE, Inc, Kittanning, Pa).”
MethodSelf-citationHellewell, S., Nguyen, V., Jayasena, R., Welton, T., & Grieve, S. (2020) · NeuroImage: Clinical · doi:10.1016/j.nicl.2020.102253 · Cited by 23
“Beyond the underlying methodology differences discussed above, these differences could be due to specific linear and/or rotational head acceleration (Kleiven 2013; Cullen et al., 2016) unique to contact sports, or other unknown factors.”
BackgroundChancellor, S. E., Franz, E. S., Minaeva, O. V., & Goldstein, L. E. (2019) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2019.03.004 · Cited by 33
Bedside to bench: the outlook for psychedelic research
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“Accordingly, our lab utilizes a porcine model of head rotational acceleration, which has been shown to produce the same tissue deformation patterns, recovery delays, neuropathology, and in fl ammation pro fi les implicated in human TBI (Cullen et al., 2016; Wofford et al., 2021; Grovola et al., 2023).”
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“Due to their gyrencephalic brains and substantial white matter, pigs have been used to model CNS disorders such as TBI (Cullen et al., 2016) and epilepsy (Van Gompel et al.”
BackgroundInfluentialSelf-citationHaber, M., Amyot, F., Lynch, C., Sandsmark, D. K., Kenney, K., Werner, J. K., Moore, C. B., Flesher, K., Woodson, S., Silverman, E., et al. (2021) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x20985156 · Cited by 19
Labyrinthine concussion: Historic otopathologic antecedents of a challenging diagnosis
Bartholomew, R. A., Lubner, R., Knoll, R. M., Ghanad, I., Jung, D. H., Nadol, J., Alvarez, V. E., Remenschneider, A., & Kozin, E. (2020) · Laryngoscope Investigative Otolaryngology · doi:10.1002/lio2.360 · Cited by 20
“are necessary to better understand the mechanisms of auditory dysfunction.(58) Our understanding of inner ear pathologies has grown and now”
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“This model requires only 15–20 min to initialize post-anesthesia and does not require a craniotomy (Cullen et al., 2016).”
Mayer, A., Ling, J., Dodd, A., Rannou-Latella, J. G., Stephenson, D., Dodd, R. J., Mehos, C. J., Patton, D., Cullen, D. K., Johnson, V., et al. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.658461 · Cited by 19
“Most dynamic non-impact acceleration models assume that biomechanical forces are limited to a single plane (73), with the plane of rotation influencing clinical (i.”
BackgroundInfluentialSelf-citationWu, T., Rifkin, J. A., Rayfield, A. C., Panzer, M. B., & Meaney, D. F. (2022) · NeuroImage · doi:10.1016/j.neuroimage.2022.119002 · Cited by 23
“For example, head rotation direction was found to significantly affect the severity and outcome of injury (Cullen et al., 2016; Gennarelli et al., 1987; Ibrahim et al., 2010).”
BackgroundSelf-citationKeating, C. E., Browne, K., Duda, J., & Cullen, D. K. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2019.6738 · Cited by 18
“To investigate damage to the oculomotor system resulting from TBI, we used a porcine model of closed-head rotational acceleration.(26,27) This well-characterized model subjects the head to rapid”
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Eckersley, C., Nightingale, R., Luck, J. F., & Bass, C. (2019) · Journal of Science and Medicine in Sport · doi:10.1016/j.jsams.2019.01.009 · Cited by 17
Reddy, D. S., Golub, V. M., Ramakrishnan, S., Churn, S. B., Shapiro, L. A., Iannucci, J., Pitkänen, A., Galanopoulou, A. S., Maganti, R. K., & Boison, D. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100080 · Cited by 18
O'Donnell, J. C., Browne, K., Kvint, S., Makaron, L., Grovola, M. R., Karandikar, S. P., Kilbaugh, T., Cullen, D. K., & Petrov, D. (2023) · Biomedicines · doi:10.3390/biomedicines11051336 · Cited by 16
“The aforementioned white:gray matter ratio and gyrencephalic cortex also influence the distribution and effects of injurious forces generated by inertial loading [22,27].”
BackgroundInfluentialSelf-citationA bioimpedance-based monitor for real-time detection and identification of secondary brain injury
Everitt, A., Root, B., Calnan, D., Manwaring, P., Bauer, D. F., & Halter, R. (2021) · Scientific Reports · doi:10.1038/s41598-021-94600-y · Cited by 16
Translational models of mild traumatic brain injury tissue biomechanics
Zhan, X., Oeur, A., Liu, Y., Zeineh, M., Grant, G. A., Margulies, S. S., & Camarillo, D. B. (2022) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2022.100422 · Cited by 19
Self-citationArmstead, W., & Vavilala, M. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2018.6119 · Cited by 15
“included scaling to accommodate for the difference in brain mass between swine and humans and use of bite plates so that the controlled angular head rotation in the pig could be achieved.(43) In contrast to the coronal rotation used in primates, in the pigs it was observed that the axial rotation produced widespread D…”
MethodHuber, C., Patton, D., Wofford, K. L., Margulies, S. S., Cullen, D. K., & Arbogast, K. (2020) · Journal of Biomechanical Engineering · doi:10.1115/1.4048574 · Cited by 15
Self-citationChallenges and Demand for Modeling Disorders of Consciousness following Traumatic Brain Injury
O'Donnell, J. C., Browne, K., Kilbaugh, T. J., Chen, H., Whyte, J., & Cullen, D. (2018) · Neuroscience and Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.12.015 · Cited by 15
Self-citationBalakin, E. I., Yurku, K. A., Fomina, T., Butkova, T. V., Игоревна, Н. В., Izotov, A., Kaysheva, A. L., & Pustovoyt, V. I. (2024) · Biology · doi:10.3390/biology13100813 · Cited by 13
“The studies on pigs were the only models to come close to imitating the diffuse axonal brain injury associated with rotational forces [109,130–133].”
BackgroundSex differences in the extent of acute axonal pathologies after experimental concussion
Song, H., Tomasevich, A., Paolini, A., Browne, K. D., Wofford, K. L., Kelley, B. J., Kantemneni, E., Kennedy, J., Qiu, Y., Schneider, A. L. C., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02735-9 · Cited by 14
“The animal preparation was carried out as previously described [9, 14, 27, 28, 51].”
InfluentialSelf-citationMcNamara, E. H., Knutsen, A. K., Korotcov, A. V., Bosomtwi, A., Liu, J., Fu, A. H., Kostelnik, C., Grillakis, A. A., Spencer, H. F., Dardzinski, B. J., et al. (2022) · Journal of Neurotrauma · doi:10.1089/neu.2021.0494 · Cited by 12
Sundaresh, S. N., Finan, J. D., Elkin, B. S., Lee, C., Xiao, J., & Morrison, B. (2021) · Brain Multiphysics · doi:10.1016/j.brain.2021.100041 · Cited by 14
Jiang, J.-P., Dai, C., Niu, X., Sun, H.-T., Cheng, S.-X., Zhang, Z.-W., Zhu, X., Wang, Y., Zhang, T.-S., Duan, F., et al. (2018) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2018.06.025 · Cited by 14
Simple and reproducible approaches for the collection of select porcine ganglia
Meyerholz, D., & Reznikov, L. R. (2017) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2017.06.005 · Cited by 14
Ballistic response of composite helmets engineered with cellular metamaterials
Fisher, T., Kazancı, Z., & Almeida, J. H. S. (2025) · Composite structures · doi:10.1016/j.compstruct.2025.119846 · Cited by 13
Advancements in in vitro models of traumatic brain injury
Hanna, M. E., & Pfister, B. J. (2022) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2022.100430 · Cited by 13
Relationships between injury kinematics, neurological recovery, and pathology following concussion
Wofford, K. L., Grovola, M. R., Adewole, D. O., Browne, K. D., Putt, M., O’Donnell, J. C., & Cullen, D. K. (2021) · Brain Communications · doi:10.1093/braincomms/fcab268 · Cited by 15
“The device rapidly accelerates the swine’s head and induces forces scalable to clinical TBIs.18 Within this cohort, swine were subjected to coronal rotational injuries that ranged from 165 to 270 radians/s to induce an mTBI.”
InfluentialSelf-citationHarris, J., Mietus, C., Browne, K., Wofford, K. L., Keating, C. E., Brown, D. P., Johnson, B. N., Wolf, J., Smith, D. H., Cohen, A., et al. (2023) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2023.1055455 · Cited by 12
Self-citationMayer, A. R., Dodd, A. B., Dodd, R. J., Stephenson, D. D., Ling, J. M., Mehos, C. J., Patton, D. A., Robertson‐Benta, C. R., Gigliotti, A. P., Vermillion, M. S., et al. (2023) · Journal of Neurotrauma · doi:10.1089/neu.2022.0338 · Cited by 14
Potential of Soft-Shell Rugby Headgear to Mitigate Linear and Rotational Peak Accelerations
Stitt, D., Kabaliuk, N., Alexander, K., & Draper, N. (2022) · Annals of Biomedical Engineering · doi:10.1007/s10439-022-02912-5 · Cited by 14
Hyaluronidase reduced edema after experimental traumatic brain injury
Washington, P. M., Lee, C., Dwyer, M. K., Konofagou, E., Kernie, S., & Morrison, B. (2020) · Journal of Cerebral Blood Flow and Metabolism · doi:10.1177/0271678x19882780 · Cited by 12
“Although an increase in water content occurs after CCI in mice, experimental closed-head TBI in larger mammals with gyrencephalic brains, such as pigs, would allow for more representative modeling of post-traumatic edema, brain swelling, and increased ICP with its subsequent complications.(43,44) Third, the level of b…”
BackgroundHamilton, K. A., & Santhakumar, V. (2020) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2020.05.001 · Cited by 13
“Swine have been utilized to simulate human rotational injury biomechanics and have addressed circuit-level questions using slices (21,22).”
MethodCharacterizing Brain Perfusion in a Swine Model of Raised Intracranial Pressure
Abdou, H., Edwards, J., Patel, N., Stonko, D. P., Elansary, N. N., Lang, E. J., Richmond, M. J., Ptak, T., White, J. M., Scalea, T. M., et al. (2022) · Journal of Surgical Research · doi:10.1016/j.jss.2022.03.034 · Cited by 13
Song, J. Y., Fleysher, R., Ye, K. Q., Kim, M., Zimmerman, M. E., Lipton, R. B., & Lipton, M. L. (2025) · NeuroImage · doi:10.1016/j.neuroimage.2025.121019 · Cited by 10
“For example, trauma (Alisafaei et al., 2020; Cullen et al., 2016; Thatcher et al., 1997), focal cortical dysplasia (FCD) (Blackmon et al., 2015), Zika virus infection (Wu et al., 2018), progressive multifocal leukoencephalopathy (Mahajan et al., 2021), multiple sclerosis (Nasiri et al., 2023) and…”
Abrams, M. Z., Venkatraman, J., Sherman, D., Ortiz-Paparoni, M. A., Bercaw, J. R., MacDonald, R. E., Kait, J., Dimbath, E. D., Pang, D. Y., Gray, A., et al. (2024) · Annals of Biomedical Engineering · doi:10.1007/s10439-024-03563-4 · Cited by 10
“Applied accelerations to the head produce shear strain within the brain, widely considered to be a mechanism for brain injury [43].”
Wu, T., Rifkin, J. A., Rayfield, A. C., Anderson, E. D., Panzer, M. B., & Meaney, D. F. (2022) · Annals of Biomedical Engineering · doi:10.1007/s10439-022-03085-x · Cited by 12
Self-citationSharkey, J. M., Quarrington, R., Krieg, J. L., Kaukas, L., Turner, R., Leonard, A., Jones, C. F., & Corrigan, F. (2023) · Brain Research · doi:10.1016/j.brainres.2023.148475 · Cited by 9
“For example, axial-plane rotation produces more severe DAI than sagittal-plane rotation in pigs (Browne et al., 2011; Cullen et al., 2016).”
Mayer, A., Ling, J., Patton, D., Stephenson, D., Dodd, A., Dodd, R. J., Rannou-Latella, J. G., Smith, D. H., Johnson, V., Cullen, D. K., et al. (2022) · Annals of Biomedical Engineering · doi:10.1007/s10439-022-02953-w · Cited by 9
Self-citationLong-term Mortality in NFL Professional Football Players
DeKosky, S. T., Jaffee, M. S., & Bauer, R. M. (2018) · JAMA · doi:10.1001/jama.2017.20885 · Cited by 9
Grovola, M. R., Jinich, A., Paleologos, N., Arroyo, E. J., Browne, K. D., Swanson, R. L., Duda, J. E., & Cullen, D. K. (2023) · Biomedicines · doi:10.3390/biomedicines11071960 · Cited by 10
“In order to attain closed-head diffuse mild TBI in animals, we used a previously described model of head-rotational acceleration in pigs [4,6].”
BackgroundMethodSelf-citationMeasurement of relative motion of the brain and skull in the mini-pig in-vivo
Kailash, K. A., Guertler, C. A., Johnson, C. L., Okamoto, R. J., & Bayly, P. V. (2023) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2023.111676 · Cited by 8
Multiple Head Rotations Result in Persistent Gait Alterations in Piglets
Mull, M., Aderibigbe, O., Hajiaghamemar, M., Oeur, A., & Margulies, S. S. (2022) · Biomedicines · doi:10.3390/biomedicines10112976 · Cited by 8
“Particularly, we concentrated on the sagittal RNR head movement known to injure the brainstem, which plays a crucial role in balance, posture, and locomotion [43].”
BackgroundSelf-citationSwanson, R. L., Acharya, N. K., & Cifu, D. X. (2022) · Cureus · doi:10.7759/cureus.25318 · Cited by 7
“Pre-clinical TBI models encompass a wide variety of injury mechanisms and severities, all of which have documented TBI-induced cerebral microvascular pathology [24,25,29,30].”
BackgroundSharkey, J. M., Quarrington, R., Magarey, C. C., & Jones, C. F. (2022) · Journal of Neuroscience Research · doi:10.1002/jnr.25049 · Cited by 8
“This could be important because evidence from animal studies (primate and pig) indicates that severity of DAI is dependent on the direction of head rotation (Browne et al., 2011; Cullen et al., 2016; Gennarelli et al., 1982; Ross et al., 1994).”
BackgroundMethodWalter, A. E., Herrold, A. A., Gallagher, V. T., Lee, R., Scaramuzzo, M., Bream, T., Seidenberg, P. H., Vandenbergh, D. J., O’Connor, K. P., Talavage, T. M., et al. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2017.5622 · Cited by 10
“82 The TAI model of head trauma provides a compelling basis for the long-term neuropathological processes leading to subsequent neurodegeneration and CTE, along with multiple functional brain disorders such as depression, general anxiety, and suicidality (for review, see Johnson and associates,…”
Labastida, J. A., Motamedi, M., Wu, P., & Szczesny, B. (2024) · STAR Protocols · doi:10.1016/j.xpro.2024.103370 · Cited by 7
Fogarty, A., Guay, C. S., Simoneau, G., Colorado, B. S., Segal, G., Werner, J., & Ellenbogen, J. (2019) · American Journal of Physical Medicine & Rehabilitation · doi:10.1097/phm.0000000000001205 · Cited by 7
Knoll, R. M., Reinshagen, K., Barber, S. R., Ghanad, I., Swanson, R., Smith, D. H., Abdullah, K., Jung, D. H., Remenschneider, A., & Kozin, E. (2018) · Journal of Neurotrauma · doi:10.1089/neu.2018.5808 · Cited by 7
“In particular, there is a predilection for the use of large animal models with closed-head injury because of their capability to replicate tissuelevel biomechanics.(24)”
BackgroundSelf-citationPeripheral immune cell dysregulation following diffuse traumatic brain injury in pigs
Wofford, K. L., Browne, K. D., Loane, D. J., Meaney, D. F., & Cullen, D. K. (2024) · Journal of Neuroinflammation · doi:10.1186/s12974-024-03317-y · Cited by 8
“This generates rotational forces scalable to clinical TBIs [26, 34, 35].”
Self-citationOeur, A., Torp, W. H., Arbogast, K. B., Master, C. L., & Margulies, S. S. (2023) · Biomedicines · doi:10.3390/biomedicines11071816 · Cited by 6
“The bite plate was attached to a linkage system that transfers the linear motion of the pneumatic actuator to a rapid head rotation of the snout and head [32,41].”
BackgroundSelf-citationStitt, D., Kabaliuk, N., Alexander, K., & Draper, N. (2022) · Annals of Biomedical Engineering · doi:10.1007/s10439-022-03045-5 · Cited by 6
Zhao, X., & He, Z. (2025) · Neuroscience Research · doi:10.1016/j.neures.2025.104979 · Cited by 5
Hippocampal interneuronal dysfunction and hyperexcitability in a porcine model of concussion
Ulyanova, A. V., Adam, C. D., Cottone, C., Maheshwari, N., Grovola, M. R., Fruchet, O., Alamar, J., Koch, P. F., Johnson, V. E., Cullen, D. K., et al. (2023) · Communications Biology · doi:10.1038/s42003-023-05491-w · Cited by 12
Self-citationGuenther, T. M., Spruce, M., Bach, L., Caples, C. M., Beyer, C., Grayson, J. K., Meyers, F., Palmieri, T., & Brown, I. (2020) · Shock · doi:10.1097/shk.0000000000001658 · Cited by 5
“Swine TBI models have also been developed, including the use of controlled cortical impact devices, fluid percussion, and penetrating objects (12, 17, 18).”
BackgroundAderibigbe, O., Wood, L. B., & Margulies, S. S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26083531 · Cited by 6
“PA, USA) [173].”
Self-citationStitt, D., Kabaliuk, N., Alexander, K., & Draper, N. (2024) · Sports Medicine - Open · doi:10.1186/s40798-024-00744-2 · Cited by 4
Porcine Astrocytes and Their Relevance for Translational Neurotrauma Research
Purvis, E. M., Fedorczak, N., Prah, A., Han, D. J., & O’Donnell, J. C. (2023) · Biomedicines · doi:10.3390/biomedicines11092388 · Cited by 5
“…high-fidelity models for the translational study of acquired brain injury due to their large gyrencephalic brains, structural similarities in limbic, subcortical, diencephalic, and brainstem regions, high white-to-gray matter ratio, and similar basal cistern geometry, among other features [14–22].”
BackgroundGeometric and Inertial Properties of the Pig Head and Brain in an Anatomical Coordinate System
Soltan, N., Siegmund, G., Cripton, P., & Jones, C. F. (2023) · Annals of Biomedical Engineering · doi:10.1007/s10439-023-03294-y · Cited by 4
“…since injury severity can be dependent on the impact direction relative to anatomical features (e.g., orientation of spine axis to the brain) [8, 31], developing an anatomically-relevant head coordinate system for the quadrupedal pig can be used to translate kinematics data to bipedal human…”
BackgroundMethodInfluentialOeur, A., Mull, M., Riccobono, G., Arbogast, K., Ciuffreda, K., Joshi, N., Fedonni, D., Master, C., & Margulies, S. S. (2023) · Biomedicines · doi:10.3390/biomedicines11020587 · Cited by 4
“With particular relevance to this study, an additional advantage of the large animal piglet model is that the conventional clinical equipment used in the clinical setting for humans can be used to study pigs [30], thereby facilitating the translation between species.”
BackgroundSelf-citationRegional variations distinguish auditory from visual evoked potentials in healthy 4 week old piglets
Oeur, R. A., Palaniswamy, M., Ha, M., Fernández-Corazza, M., & Margulies, S. (2023) · Physiological Measurement · doi:10.1088/1361-6579/acb4da · Cited by 4
Self-citationTranslationally Relevant Magnetic Resonance Imaging Markers in a Ferret Model of Closed Head Injury
Hutchinson, E., Romero-Lozano, A., Johnson, H. R., Knutsen, A. K., Bosomtwi, A., Korotcov, A., Shunmugavel, A., King, S., Schwerin, S., Juliano, S., et al. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.779533 · Cited by 4
“A second approach to improving the translational relevance of pre-clinical TBI models is to consider experiments in nonrodent species, especially those with neuroanatomic features that are more similar to the human brain including swine, nonhuman primates, and ferrets (Manley et al., 2006; MorgantiKossmann et al., 201…”
BackgroundZhang, X., Li, C., Yan, Y., Nair, G., Rilling, J. K., Herndon, J. G., Preuss, T. M., Hu, X., & Li, L. (2020) · Magnetic Resonance Imaging · doi:10.1016/j.mri.2020.12.015 · Cited by 4
“In addition, large animals (like pigs) have irregular head geometry and have been increasingly used for studies in stroke [91-93] and traumatic brain injury [94, 95].”
BackgroundTarget detection in healthy 4-week old piglets from a passive two-tone auditory oddball paradigm
Oeur, R., & Margulies, S. S. (2020) · BMC Neuroscience · doi:10.1186/s12868-020-00601-4 · Cited by 4
Self-citationMechanical characterization of human versus porcine brain tissue under large strains
Reiter, N., Nistler, S., Hoffmann, L., Bräuer, L., Paulsen, F., & Budday, S. (2026) · Biomechanics and Modeling in Mechanobiology · doi:10.1007/s10237-025-02040-8 · Cited by 3
“…transferrable between species, studies that look at age-dependent trends and thus require samples of a defined age range (Prange and Margulies 2002; Hoppstädter et al. 2024), or studies that involve mechanical impacts on the living brain (Browne et al. 2011; Cullen et al. 2016; Wolf et al. 2017).”
Mild and repetitive mild traumatic brain injury: Changes in microglial cells and synapses
Smajkan, A., Naranjo-Cinto, E., & Bareyre, F. M. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-25-00902 · Cited by 2
“Large animal models provide several advantages, including brain anatomy, biomechanics, and white matter composition that more closely reflect human physiology (Cullen et al., 2016; Vink, 2018).”
Huber, C., Thakore, A. D., Oeur, A., & Margulies, S. S. (2025) · Biomedicines · doi:10.3390/biomedicines13102547 · Cited by 3
“…provide a particularly compelling, well-established model for preclinical TBI studies [25–27] due to similarities in neuroanatomical structure with humans, including a gyrencephalic brain and comparable white to grey matter ratios, allowing accurate representation of injury biomechanics [28–31].”
Self-citationPatton, D., Grunig, C. S., McQuaid, J. R., Dodd, A., Pacheco, M. K., Ling, J. M., Wick, T. V., Kumar, D. S., Zotev, V., Kinsler, R., et al. (2025) · Annals of Biomedical Engineering · doi:10.1007/s10439-025-03736-9 · Cited by 3
“Large mammals have gyrencephalic brains with substantial white matter domains and are particularly useful for studying tissue-level biomechanics of TBI [5].”
InfluentialHuber, C. M., Thakore, A. D., Oeur, A., & Margulies, S. S. (2024) · Journal of Neurotrauma · doi:10.1089/neu.2023.0660 · Cited by 4
“25,26 In addition, piglet brains exhibit developmental similarities to the pediatric brain in myelination timeline and white matter volume, aiding researchers in studying neurological conditions throughout development in both species.”
Self-citation
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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