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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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.
“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 · see citing works
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 · see citing works
Langlois, J., Rutland-Brown, W., & Thomas, K. (2006) · PsycEXTRA Dataset · doi:10.1037/e721222007-001 · Cited by 3,003 · see citing works
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 · see citing works
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× · see citing works
“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 1,413 · cited 1× · see citing works
“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 · see citing works
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× · see citing works
“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 · see citing works
Classification of traumatic brain injury for targeted therapies
Saatman, K. E., Duhaime, A.-C., Bullock, R., Maas, A. I. R., Valadka, A., & Manley, G. T. (2008) · Journal of Neurotrauma · doi:10.1089/neu.2008.0586 · Cited by 1,141 · cited 1× · see citing works
“While the lack of positive findings in clinical studies may reflect the complexity and heterogeneity of human TBI and challenges in clinical trial design [28], it may also serve as a cautionary tale of the inability of rodent models to replicate the pathophysiology and neurodegenerative sequelae of clinical TBI [49].”
Inflammation and white matter degeneration persist for years after a single traumatic brain injury
Johnson, V. E., Stewart, J. E., Begbie, F. D., Trojanowski, J. Q., Smith, D. H., & Stewart, W. (2013) · Brain · doi:10.1093/brain/aws322 · Cited by 1,045 · see citing works
Self-citationOMMAYA, A. K., & GENNARELLI, T. A. (1974) · Brain · doi:10.1093/brain/97.1.633 · Cited by 1,026 · cited 1× · see citing works
“In addition, animal studies have shown that purely linear motions produce little brain deformation or distortion and no concussion [50, 154, 155].”
In vivo1H NMR spectroscopy of rat brain at 1 ms echo time
Tk�?, I., uk, Z. S., Choi, I., & Rolf Gruetter, A. (1999) · Magnetic Resonance in Medicine · doi:10.1002/(sici)1522-2594(199904)41:4 · Cited by 994 · see citing works
Self-citationDiffuse axonal injury due to nonmissile head injury in humans: An analysis of 45 cases
Adams, J. H., Graham, D. I., Murray, L. S., & Scott, G. (1982) · Annals of Neurology · doi:10.1002/ana.410120610 · Cited by 950 · see citing works
A universal scaling law between gray matter and white matter of cerebral cortex
Zhang, K., & Sejnowski, T. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090504197 · Cited by 723 · see citing works
Chronic neuropathologies of single and repetitive TBI: substrates of dementia?
Smith, D. H., Johnson, V. E., & Stewart, W. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.29 · Cited by 699 · see citing works
Self-citationHolbourn, A. (1943) · The Lancet · doi:10.1016/s0140-6736(00)87453-x · Cited by 681 · see citing works
Disability in young people and adults one year after head injury: prospective cohort study
Thornhill, S., Teasdale, G., Murray, G., Mcewen, J., Roy, C., & Penny, K. (2000) · British medical journal · doi:10.1136/bmj.320.7250.1631 · Cited by 679 · see citing works
Predictors for Traumatic Brain Injuries Evaluated through Accident Reconstructions
Kleiven, S. (2007) · SAE technical papers on CD-ROM/SAE technical paper series · doi:10.4271/2007-22-0003 · Cited by 676 · cited 1× · see citing works
“head (linear and rotational accelerations), and the predicted diffuse strain fields in the brain [156, 157].”
Update of Neuropathology and Neurological Recovery After Traumatic Brain Injury
Povlishock, J. T., & Katz, D. I. (2005) · Journal of Head Trauma Rehabilitation · doi:10.1097/00001199-200501000-00008 · Cited by 676 · see citing works
Diffuse Axonal Injury in Head Trauma
Smith, D. H., Meaney, D., & Shull, W. H. (2003) · The journal of head trauma rehabilitation · doi:10.1097/00001199-200307000-00003 · Cited by 627 · see citing works
Self-citationWidespread tau and amyloid-beta pathology many years after a single traumatic brain injury in humans
Johnson, V. E., Stewart, W., & Smith, D. H. (2012) · Brain Pathology · doi:10.1111/j.1750-3639.2011.00513.x · Cited by 620 · cited 1× · see citing works
“Specifically, many of these proteins are the primary constituents of the pathologic inclusions found in several neurode-generative diseases [19, 31, 142, 145].”
Self-citationYoshino, A., Hovda, D. A., Kawamata, T., Katayama, Y., & Becker, D. P. (1991) · Brain Research · doi:10.1016/0006-8993(91)90755-k · Cited by 592 · see citing works
Traumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease?
Johnson, V. E., Stewart, W., & Smith, D. H. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2808 · Cited by 587 · see citing works
Self-citationLoane, D. J., & Faden, A. I. (2010) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2010.09.005 · Cited by 574 · see citing works
Cell Death Mechanisms Following Traumatic Brain Injury
Raghupathi, R. (2004) · Brain Pathology · doi:10.1111/j.1750-3639.2004.tb00056.x · Cited by 565 · see citing works
Hardy, W., Foster, C., Mason, M., Yang, K. H., King, A., & Tashman, S. (2001) · Stapp Car Crash Journal · doi:10.4271/2001-22-0016 · Cited by 529 · cited 1×
“In addition, animal studies have shown that purely linear motions produce little brain deformation or distortion and no concussion [50, 154, 155].”
A proposed tolerance criterion for diffuse axonal injury in man.
Margulies, S. S., & Thibault, L. (1992) · Journal of Biomechanics · doi:10.1016/0021-9290(92)90231-o · Cited by 487 · cited 1× · see citing works
“To further establish links between macro- and micro-biomechanical features as well as to advance scaling to human injuries, the HYGE device has been used to subject physical models of the skull brain structures to identical loading conditions used to produce specific brain injuries in animals [63, 65, 66, 104, 126].”
Self-citationMolecular mechanisms of calcium-dependent excitotoxicity
Sattler, R., & Tymianski, M. (2000) · Journal of Molecular Medicine · doi:10.1007/s001090000077 · Cited by 477 · see citing works
HEAD IMPACT SEVERITY MEASURES FOR EVALUATING MILD TRAUMATIC BRAIN INJURY RISK EXPOSURE
Greenwald, R., Gwin, J. T., Chu, J., & Crisco, J. (2008) · Neurosurgery · doi:10.1227/01.neu.0000318162.67472.ad · Cited by 476 · see citing works
Traumatically Induced Axonal Injury: Pathogenesis and Pathobiological Implications
Povlishock, J. (1991) · Brain Pathology · doi:10.1111/j.1750-3639.1991.tb00050.x · Cited by 475 · see citing works
Axonal Change in Minor Head Injury
Povlishock, J., Becker, D., Cheng, C. L. Y., & Vaughan, G. (1983) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-198305000-00002 · Cited by 461 · see citing works
Concussion in professional football: reconstruction of game impacts and injuries.
Gordon, A. (2004) · Neurosurgery · doi:10.1227/01.neu.0000129105.28087.59b · Cited by 454
Progressive atrophy and neuron death for one year following brain trauma in the rat
Smith, D. H., Chen, X.-H., Pierce, J. E. S., Wolf, J. A., Trojanowski, J. Q., Graham, D. I., & McIntosh, T. K. (1997) · Journal of Neurotrauma · doi:10.1089/neu.1997.14.715 · Cited by 440 · see citing works
Self-citationAnalysis of Real-time Head Accelerations in Collegiate Football Players
Duma, S., Manoogian, S., Bussone, W. R., Brolinson, P. G., Goforth, M., Donnenwerth, J., Greenwald, R., Chu, J., & Crisco, J. (2005) · Clinical Journal of Sports Medicine · doi:10.1097/00042752-200501000-00002 · Cited by 429 · see citing works
Trends in Traumatic Brain Injury in the U.S. and the public health response: 1995–2009
Coronado, V. G., McGuire, L., Sarmiento, K., Bell, J. M., Lionbarger, M. R., Jones, C. D., Geller, A. I., Khoury, N. M., & Xu, L. (2012) · Journal of Safety Research · doi:10.1016/j.jsr.2012.08.011 · Cited by 420 · see citing works
Physical model simulations of brain injury in the primate.
Margulies, S., Thibault, L., & Gennarelli, T. (1990) · Journal of Biomechanics · doi:10.1016/0021-9290(90)90029-3 · Cited by 412 · cited 1× · see citing works
“To further establish links between macro- and micro-biomechanical features as well as to advance scaling to human injuries, the HYGE device has been used to subject physical models of the skull brain structures to identical loading conditions used to produce specific brain injuries in animals [63, 65, 66, 104, 126].”
Self-citationA study of the response of the human cadaver head to impact.
Hardy, W., Mason, M., Foster, C., Shah, C., Kopacz, J. M., Yang, K. H., King, A., Bishop, J. L., Bey, M., Anderst, W., et al. (2007) · Stapp Car Crash Journal · doi:10.4271/2007-22-0002 · Cited by 411 · see citing works
Leininger, B. E., Gramling, S. E., Farrell, A., Kreutzer, J., & Peck, E. (1990) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.53.4.293 · Cited by 383 · see citing works
Axonal Damage in Traumatic Brain Injury
Smith, D. H., & Meaney, D. (2000) · The Neuroscientist · doi:10.1177/107385840000600611 · Cited by 372 · cited 2× · see citing works
“DAI is a major feature of closed-head diffuse brain injury in swine, and manifests as accumulation of axonal transport proteins such as amyloid precursor protein (APP) in swollen regions of axons with eventual degeneration in stereotypical distribution suggestive of a biomechanical etiology [30, 140] (Fig.”
Self-citationUryu, K., Chen, X.-H., Martinez, D., Browne, K. D., Johnson, V. E., Graham, D. I., Lee, V. M.-Y., Trojanowski, J. Q., & Smith, D. H. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.06.018 · Cited by 360 · cited 1× · see citing works
“Specifically, many of these proteins are the primary constituents of the pathologic inclusions found in several neurode-generative diseases [19, 31, 142, 145].”
Self-citationThe clinical spectrum of sport-related traumatic brain injury
Jordan, B. D. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.33 · Cited by 347 · see citing works
Calcium and Excitotoxic Neuronal Injury
Choi, D. W. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb44407.x · Cited by 344 · see citing works
Mouzon, B., Bachmeier, C. J., Ferro, A., Ojo, J., Crynen, G. C., Acker, C. M., Davies, P., MULLAN, M. J., Stewart, W. B., Jr., & Crawford, F. (2013) · Annals of Neurology · doi:10.1002/ana.24064 · Cited by 331 · see citing works
Tang-Schomer, M., Johnson, V., Baas, P. W., Stewart, W., & Smith, D. H. (2011) · Experimental Neurology · doi:10.1016/j.expneurol.2011.10.030 · Cited by 330 · see citing works
Self-citationA proposed new biomechanical head injury assessment function - the maximum power index.
Newman, J. A., Shewchenko, N., & Welbourne, E. (2000) · Stapp Car Crash Journal · doi:10.4271/2000-01-sc16 · Cited by 326 · see citing works
Howells, D. W., Porritt, M. J., Rewell, S. S., O'Collins, V., Sena, E. S., van der Worp, H. B., Traystman, R. J., & Macleod, M. R. (2010) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2010.66 · Cited by 309 · see citing works
The costs of traumatic brain injury: a literature review
Humphreys, I., Wood, R., Phillips, C., & Macey, S. (2013) · ClinicoEconomics and Outcomes Research · doi:10.2147/ceor.s44625 · Cited by 296 · see citing works
Concussion in Professional Football: Reconstruction of Game Impacts and Injuries
Pellman, E. J., Viano, D., Tucker, A., Casson, I., & Waeckerle, J. F. (2003) · Neurosurgery · doi:10.1227/01.neu.0000083559.68424.3f · Cited by 293 · see citing works
Chen, X.-H., Siman, R., Iwata, A., Meaney, D. F., Trojanowski, J. Q., & Smith, D. H. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63303-2 · Cited by 271 · see citing works
Self-citationSmith, D. H., Chen, X.-H., Nonaka, M., Trojanowski, J. Q., Lee, V.-Y., Saatman, K. E., Leoni, M. J., Xu, B.-N., Wolf, J. A., & Meaney, D. F. (1999) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199909000-00008 · Cited by 260 · see citing works
Self-citationLaPlaca, M., Cullen, D., McLoughlin, J., & Cargill, R. S. (2005) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2004.05.032 · Cited by 258 · see citing works
Self-citationMechanical and electrical responses of the squid giant axon to simple elongation.
Galbraith, J., Thibault, L., & Matteson, D. (1993) · Journal of Biomechanical Engineering · doi:10.1115/1.2895464 · Cited by 256 · see citing works
Biomechanical Analysis of Experimental Diffuse Axonal Injury
MEANEY, D. F., SMITH, D. H., SHREIBER, D. I., BAIN, A. C., MILLER, R. T., ROSS, D. T., & GENNARELLI, T. A. (1995) · Journal of Neurotrauma · doi:10.1089/neu.1995.12.689 · Cited by 254 · cited 3× · see citing works
“Indeed, when angular acceleration is scaled based on the relative masses of human and pig brains, the loading conditions generated closely approximate the conditions of inertial brain injury in humans [64, 114].”
Self-citationEmbracing failure: What the Phase III progesterone studies can teach about TBI clinical trials
Stein, D. G. (2015) · Brain Injury · doi:10.3109/02699052.2015.1065344 · Cited by 249 · cited 1× · see citing works
“Unfortunately, despite reports of hundreds of treatments that have show efficacy in rodent models of TBI, none have translated to clinical use despite over 30 clinical trials based on the preclinical data [47, 48].”
McIntosh, Saatman, Raghupathi, Graham, Smith, Lee, & Trojanowski (1998) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.1998.00121.x · Cited by 249 · see citing works
Mild traumatic brain injury and diffuse axonal injury in swine
Browne, K. D., Chen, X.-H., Meaney, D. F., & Smith, D. H. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2011.1913 · Cited by 248 · cited 5× · see citing works
“Recently, we have used these simplified scaling relationships to transfer the rotational accelerations associated with concussion in humans, described in recent studies to be 5600–8000 rad/s [128 – 132], to equivalent rotational motions in the smaller young adult swine brain [114].”
InfluentialSelf-citationThe mechanics of brain injuries
Holbourn, A. (1945) · British Medical Bulletin · doi:10.1093/oxfordjournals.bmb.a071895 · Cited by 245 · see citing works
Delayed and progressive brain injury in closed-head trauma: radiological demonstration.
Stein, S., Spettell, C., Young, G. S., & Ross, S. (1993) · Neurosurgery · doi:10.1227/00006123-199301000-00004 · Cited by 235 · see citing works
Smith, D. H., Chen, X. H., Xu, B. N., McIntosh, T., Gennarelli, T., & Meaney, D. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199756070-00009 · Cited by 231 · cited 18× · see citing works
“Prominent changes have varied based on neuroanatomical locale and severity of head rotation, and include astrogliosis, neuro-inflammation, perikaryal degeneration and multifocal DAI (Fig.”
InfluentialSelf-citationCNS injury biomechanics and experimental models
LaPlaca, M. C., Simon, C. M., Prado, G. R., & Cullen, D. K. (2007) · Progress in brain research · doi:10.1016/s0079-6123(06)61002-9 · Cited by 224 · see citing works
Self-citationMild Traumatic Brain Injury Predictors Based on Angular Accelerations During Impacts
Kimpara, H., & Iwamoto, M. (2011) · Annals of Biomedical Engineering · doi:10.1007/s10439-011-0414-2 · Cited by 223 · see citing works
Pathophysiologic Responses to Rotational and Translational Accelerations of the Head
Gennarelli, T., Thibault, L., & Ommaya, A. (1972) · SAE technical papers on CD-ROM/SAE technical paper series · doi:10.4271/720970 · Cited by 217 · see citing works
Ommaya, A., Hirsch, A., Yarnell, P., & Harris, E. H. (1967) · SAE technical papers on CD-ROM/SAE technical paper series · doi:10.4271/670906 · Cited by 217 · see citing works
Immediate coma following inertial brain injury dependent on axonal damage in the brainstem.
Smith, D. H., Nonaka, M., Miller, R., Leoni, M., Chen, X. H., Alsop, D., & Meaney, D. (2000) · Journal of Neurosurgery · doi:10.3171/jns.2000.93.2.0315 · Cited by 213 · cited 19× · see citing works
“Prominent changes have varied based on neuroanatomical locale and severity of head rotation, and include astrogliosis, neuro-inflammation, perikaryal degeneration and multifocal DAI (Fig.”
InfluentialSelf-citationGeddes, D. M., Cargill, R. S., & LaPlaca, M. C. (2003) · Journal of Neurotrauma · doi:10.1089/089771503770195885 · Cited by 207 · see citing works
Traumatic brain injury, neuroimaging, and neurodegeneration
Bigler, E. D. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00395 · Cited by 205 · see citing works
Ommaya, A., Grubb, R. L., & Naumann, R. A. (1971) · Journal of Neurosurgery · doi:10.3171/jns.1971.35.5.0503 · Cited by 200 · cited 1× · see citing works
“In addition, animal studies have shown that purely linear motions produce little brain deformation or distortion and no concussion [50, 154, 155].”
Amyloid β accumulation in axons after traumatic brain injury in humans
Smith, D. H., Chen, X.-H., Iwata, A., & Graham, D. (2003) · Journal of neurosurgery · doi:10.3171/jns.2003.98.5.1072 · Cited by 196 · see citing works
Self-citationTraumatic Axonal Injury is Exacerbated following Repetitive Closed Head Injury in the Neonatal Pig
Raghupathi, R., Mehr, M. F., Helfaer, M., & Margulies, S. (2004) · Journal of Neurotrauma · doi:10.1089/089771504322972095 · Cited by 189 · see citing works
Self-citationNeuroprotective Strategies for Traumatic Brain Injury: Improving Clinical Translation
Kabadi, S. V., & Faden, A. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms15011216 · Cited by 183 · cited 1× · see citing works
“Unfortunately, despite reports of hundreds of treatments that have show efficacy in rodent models of TBI, none have translated to clinical use despite over 30 clinical trials based on the preclinical data [47, 48].”
Cullen, D., Simon, C. M., & LaPlaca, M. (2007) · Brain Research · doi:10.1016/j.brainres.2007.04.070 · Cited by 178 · see citing works
Self-citationDiffuse optical monitoring of hemodynamic changes in piglet brain with closed head injury
Zhou, C., Eucker, S. A., Durduran, T., Yu, G., Ralston, J., Friess, S. H., Ichord, R., Margulies, S. S., & Yodh, A. G. (2009) · Journal of Biomedical Optics · doi:10.1117/1.3146814 · Cited by 175 · see citing works
Self-citationIntravascular coagulation: a major secondary insult in nonfatal traumatic brain injury.
Stein, S., Chen, X.-H., Sinson, G., & Smith, D. H. (2002) · Journal of Neurosurgery · doi:10.3171/jns.2002.97.6.1373 · Cited by 175 · see citing works
Self-citationDemetriades, D., Kuncir, E., Murray, J., Velmahos, G., Rhee, P., & Chan, L. (2004) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2004.02.030 · Cited by 168 · cited 1× · see citing works
“However, approximately 90 % of clinical TBIs are classified as mild, which by definition are closed-head injuries and not typically associated with bleeds or contusions, although there is debate in this area [53, 54].”
Gennarelli, T., Adams, J., & Graham, D. (1981) · Acta neuropathologica. Supplementum · doi:10.1007/978-3-642-81553-9_7 · Cited by 165 · cited 1× · see citing works
“It has been demonstrated that diffuse brain injury thresholds and outcomes depend on the direction of head motion as well as on the magnitude of rotational kinematics [94, 126].”
Miller, R. T., Margulies, S., Leoni, M., Nonaka, M., Chen, X.-H., Smith, D. H., & Meaney, D. (1998) · SAE technical papers on CD-ROM/SAE technical paper series · doi:10.4271/983154 · Cited by 156 · cited 1× · see citing works
“In addition, we previously determined that axial plane accelerations in pigs caused increased localized strains in the brainstem region [133] compared to coronal plane accelerations, so we therefore calculated a proportionally lower level of peak rotational acceleration in this plane of 14,000–30,000 rad/s (correspond…”
Self-citationTraumatic Axonal Injury after Closed Head Injury in the Neonatal Pig
Raghupathi, R., & Margulies, S. (2002) · Journal of Neurotrauma · doi:10.1089/08977150260190438 · Cited by 152 · cited 1×
“Angular displacement is calculated by integrating the angular velocity, whereas angular acceleration is calculated by taking the derivative of the angular velocity as described [107].”
Self-citationTemporal development of hippocampal cell death is dependent on tissue strain but not strain rate.
Cater, H. L., Sundstrom, L., & Morrison, B. (2006) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2005.09.023 · Cited by 150
LaPlaca, M., Lee, V., & Thibault, L. E. (1997) · Journal of Neurotrauma · doi:10.1089/neu.1997.14.355 · Cited by 148 · see citing works
Region-Specific Tolerance Criteria for the Living Brain
Elkin, B. S., & Morrison, B. (2007) · SAE technical papers on CD-ROM/SAE technical paper series · doi:10.4271/2007-22-0005 · Cited by 143 · see citing works
Monti, J. M., Voss, M. W., Pence, A., McAuley, E., Kramer, A. F., & Cohen, N. J. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00041 · Cited by 138 · cited 1× · see citing works
“Across the severity spectrum of TBI, outcomes vary from temporary, mild cognitive deficits to permanent, severely debilitating changes affecting motor function, emotion, and cognition [41, 42].”
Ross, D. T., Meaney, D., Sabol, M., Smith, D. H., & Gennarelli, T. (1994) · Experimental Neurology · doi:10.1006/exnr.1994.1067 · Cited by 130 · cited 1× · see citing works
“In particular, hippocampal neuronal degeneration has been shown only following relatively high head rotational levels (often complicated by hematoma) but not lower levels associated with concussion [79, 95, 114, 134].”
Self-citationHutson, C. B., Lazo, C. R., Mortazavi, F., Giza, C. C., Hovda, D. A., & Chesselet, M. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2010.1723 · Cited by 129 · see citing works
Potential Animal Models of Lacunar Stroke: A Systematic Review
Bailey, E. L., McCulloch, J., Sudlow, C., & Wardlaw, J. M. (2009) · Stroke · doi:10.1161/strokeaha.108.528430 · Cited by 128 · see citing works
Vanderploeg, R., Crowell, T., & Curtiss, G. (2001) · Journal of Clinical and Experimental Neuropsychology · doi:10.1076/jcen.23.2.185.1210 · Cited by 127
Selective Vulnerability of Hippocampal Neurons in Acceleration-Induced Experimental Head Injury
Kotapka, M., Gennarelli, T., Graham, D. I., Adams, J., Thibault, L. E., Ross, D. T., & Ford, I. (1991) · Journal of Neurotrauma · doi:10.1089/neu.1991.8.247 · Cited by 124 · see citing works
Age-dependent synuclein pathology following traumatic brain injury in mice.
Uryu, K., Giasson, B. I., Longhi, L., Martinez, D., Murray, I. V. J., Conte, V., Nakamura, M., Saatman, K., Talbot, K., Horiguchi, T., et al. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00245-0 · Cited by 113 · see citing works
An analytical model of traumatic diffuse brain injury.
Margulies, S. S., & Thibault, L. (1989) · Journal of Biomechanical Engineering · doi:10.1115/1.3168373 · Cited by 113 · cited 1× · see citing works
“To further establish links between macro- and micro-biomechanical features as well as to advance scaling to human injuries, the HYGE device has been used to subject physical models of the skull brain structures to identical loading conditions used to produce specific brain injuries in animals [63, 65, 66, 104, 126].”
Self-citationCullen, D., Vernekar, V. N., & LaPlaca, M. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2011.1841 · Cited by 112 · cited 1× · see citing works
“Moreover, in closed-head diffuse brain injury, the dominant mode of brain tissue deformation is shear strain, owing to the shear modulus being at least several orders of magnitude lower than the bulk modulus of brain tissue [56, 70, 80, 81].”
Self-citationCerebral Concussion in the Monkey: An Experimental Model
Ommaya, A., Hirsch, A., Flamm, E., & Mahone, R. H. (1966) · Science · doi:10.1126/science.153.3732.211 · Cited by 112 · cited 1×
“Moreover, the time over which head rotation occurs is an important component of injury thresholds, as animal studies have indicated that the incidence of concussion increases when the duration of rotational acceleration is increased [57].”
Repeated Traumatic Brain Injury Affects Composite Cognitive Function in Piglets
Friess, S. H., Ichord, R., Ralston, J., Ryall, K. A., Helfaer, M. A., Smith, C., & Margulies, S. S. (2009) · Journal of Neurotrauma · doi:10.1089/neu.2008.0845 · Cited by 111 · cited 1× · see citing works
“Ongoing studies are expanding the use of this model to include novel measurements as well as to translate outcomes utilized in pediatric swine, including behavioral assessment [100, 109, 146], neurophysiological changes [134, 146, 147], and multi-model neuromonitoring [101 – 103, 137].”
Self-citationEucker, S., Smith, C. M., Ralston, J., Friess, S., & Margulies, S. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.09.015 · Cited by 107 · cited 5× · see citing works
“In this fashion, this model produces pure impulsive non-impact head rotation in different planes at controlled rotational acceleration levels [64, 79, 98, 126] (Fig.”
InfluentialSelf-citationKimura, H., Meaney, D., Mcgowan, J., Grossman, R., Lenkinski, R., Ross, D. T., McIntosh, T., Gennarelli, T., & Smith, D. H. (1996) · Journal of computer assisted tomography · doi:10.1097/00004728-199607000-00007 · Cited by 107 · cited 1× · see citing works
“employed magnetization transfer ratio imaging (MTR) to correlate changes in MRI scans to histological evidence of damage, opening the door to a range of imaging modalities [99, 138].”
Self-citationEnhancement of AMPA-Mediated Current after Traumatic Injury in Cortical Neurons
Goforth, P. B., Ellis, E., & Satin, L. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-17-07367.1999 · Cited by 106 · see citing works
Evolution of neurofilament subtype accumulation in axons following diffuse brain injury in the pig.
Chen, X. H., Meaney, D., Xu, B. N., Nonaka, M., McIntosh, T., Wolf, J., Saatman, K., & Smith, D. H. (1999) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199906000-00003 · Cited by 106 · cited 14× · see citing works
“Prominent changes have varied based on neuroanatomical locale and severity of head rotation, and include astrogliosis, neuro-inflammation, perikaryal degeneration and multifocal DAI (Fig.”
InfluentialSelf-citationSmith, D. H., Lowenstein, D. H., Gennarelli, T. A., & McIntosh, T. K. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)90438-3 · Cited by 105 · see citing works
Self-citationIn vivo imaging of rapid deformation and strain in an animal model of traumatic brain injury.
Bayly, P., Black, E. E., Pedersen, R. C., Leister, E., & Genin, G. (2006) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2005.02.014 · Cited by 105
Smith, D. H., Hicks, R. R., Johnson, V. E., Bergstrom, D. A., Cummings, D. M., Noble‐Haeusslein, L. J., Hovda, D. A., Whalen, M. J., Ahlers, S. T., LaPlaca, M. C., et al. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2014.3861 · Cited by 103 · cited 1× · see citing works
“While the lack of positive findings in clinical studies may reflect the complexity and heterogeneity of human TBI and challenges in clinical trial design [28], it may also serve as a cautionary tale of the inability of rodent models to replicate the pathophysiology and neurodegenerative sequelae of clinical TBI [49].”
Self-citationSullivan, S., Eucker, S., Gabrieli, D., Bradfield, C., Coats, B., Maltese, M., Lee, J., Smith, C. M., & Margulies, S. (2014) · Biomechanics and Modeling in Mechanobiology · doi:10.1007/s10237-014-0643-z · Cited by 103 · cited 1× · see citing works
“This porcine model of non-impact closed-head rotational-acceleration induced TBI results in different neurological outcomes which are dependent on the plane of head rotation and the level of rotational acceleration/velocity [67, 98, 114, 126, 134].”
Self-citationDiagnostic criteria and differential diagnosis of mild traumatic brain injury.
de Kruijk, J. D., Twijnstra, A., & Leffers, P. (2001) · Brain Injury · doi:10.1080/026990501458335 · Cited by 103
Large Animal Models of Traumatic Injury to the Immature Brain
Duhaime, A. (2006) · Developmental Neuroscience · doi:10.1159/000094164 · Cited by 101 · cited 1× · see citing works
“The complex neuroanatomy and neurophysiology of humans and other large mammals such as pigs, denoted by gyrencephalic brains, substantial white matter domains and specific pathophysiological features, may be key factors in the development of specific features of trauma-induced neuropathology [30, 82].”
A clinical comparison of penetrating and blunt traumatic brain injuries
Santiago, L. A., Oh, B. C., Dash, P., Holcomb, J., & Wade, C. (2012) · Brain Injury · doi:10.3109/02699052.2011.635363 · Cited by 99 · cited 1× · see citing works
“However, approximately 90 % of clinical TBIs are classified as mild, which by definition are closed-head injuries and not typically associated with bleeds or contusions, although there is debate in this area [53, 54].”
Kilbaugh, T., Bhandare, S., Lorom, D. H., Saraswati, M., Robertson, C., & Margulies, S. (2011) · Journal of Neurotrauma · doi:10.1089/neu.2010.1635 · Cited by 97 · see citing works
Self-citationAlterations in calcium-mediated signal transduction after traumatic injury of cortical neurons
Weber, J. T., Rzigalinski, B. A., Willoughby, K. A., Moore, S. F., & Ellis, E. F. (1999) · Cell Calcium · doi:10.1054/ceca.1999.0082 · Cited by 95 · see citing works
Neuronal Response to High Rate Shear Deformation Depends on Heterogeneity of the Local Strain Field
Cullen, D., & LaPlaca, M. (2006) · Journal of Neurotrauma · doi:10.1089/neu.2006.23.1304 · Cited by 94 · see citing works
Self-citationVink, R., Mullins, P. G., Temple, M. D., Bao, W.-L., & Faden, A. (2001) · Journal of Neurotrauma · doi:10.1089/089771501316919201 · Cited by 87 · see citing works
Fate of reactive axonal swellings induced by head injury.
Povlishock, J., & Becker, D. (1988) · Laboratory investigation; a journal of technical methods and pathology · doi:10.1097/00001199-198806000-00012 · Cited by 87
Numerical reconstruction of real-life concussive football impacts.
Fréchède, B., & McIntosh, A. (2009) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e318186b1c5 · Cited by 86 · see citing works
Neurobehavioral functional deficits following closed head injury in the neonatal pig.
Friess, S., Ichord, R., Owens, K., Ralston, J., Rizol, R., Overall, K., Smith, C. M., Helfaer, M., & Margulies, S. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2006.10.010 · Cited by 79 · cited 1× · see citing works
“Ongoing studies are expanding the use of this model to include novel measurements as well as to translate outcomes utilized in pediatric swine, including behavioral assessment [100, 109, 146], neurophysiological changes [134, 146, 147], and multi-model neuromonitoring [101 – 103, 137].”
Self-citationMagnetic Resonance Spectroscopy of Diffuse Brain Trauma in the Pig
Smith, D. H., Cecil, K., Meaney, D., Chen, X. H., McIntosh, T., Gennarelli, T., & Lenkinski, R. (1998) · Journal of Neurotrauma · doi:10.1089/neu.1998.15.665 · Cited by 77 · cited 1× · see citing works
“Subsequent studies utilized proton magnetic resonance spectroscopy (MRS) to detect a decline in N-acetylaspartate (NAA) in areas of confirmed axonal damage and a decrease in intracellular magnesium [139].”
Self-citationGutierrez, E., Huang, Y.-L., Haglid, K. G., Bao, F., Hansson, H., Hamberger, A., & Viano, D. C. (2001) · Journal of Neurotrauma · doi:10.1089/08977150151070874 · Cited by 75 · cited 1× · see citing works
“It is a significant challenge to achieve sufficient head rotational acceleration in small rodents to mimic the tissue-level forces without inducing compression effects or rupture of the vasculature, although some have proposed models for this purpose [83, 84].”
Long-Term Dysfunction Following Diffuse Traumatic Brain Injury in the Immature Rat
Adelson, P. D., Dixon, C. E., & Kochanek, P. M. (2000) · Journal of Neurotrauma · doi:10.1089/neu.2000.17.273 · Cited by 75 · see citing works
The Pathobiology of Traumatic Brain Injury
Gennarelli, T. (1997) · The Neuroscientist · doi:10.1177/107385849700300117 · Cited by 71 · see citing works
High‐Field Proton Magnetic Resonance Spectroscopy of a Swine Model for Axonal Injury
Cecil, K., Lenkinski, R., Meaney, D., McIntosh, T., & Smith, D. H. (1998) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1998.70052038.x · Cited by 69 · see citing works
Self-citationHead injury in the chimpanzee. 1. Biodynamics of traumatic unconsciousness.
Ommaya, A., Corrao, P., & Letcher, F. (1973) · Journal of Neurosurgery · doi:10.3171/jns.1973.39.2.0152 · Cited by 69
New Rat Model for Diffuse Brain Injury Using Coronal Plane Angular Acceleration
Fijalkowski, R. J., Stemper, B., Pintar, F., Yoganandan, N., Crowe, M., & Gennarelli, T. (2007) · Journal of Neurotrauma · doi:10.1089/neu.2007.0268 · Cited by 67 · cited 1× · see citing works
“It is a significant challenge to achieve sufficient head rotational acceleration in small rodents to mimic the tissue-level forces without inducing compression effects or rupture of the vasculature, although some have proposed models for this purpose [83, 84].”
Acceleration induced head injury in the monkey. II. Neuropathology.
Adams, J., Graham, D., & Gennarelli, T. (1981) · Acta neuropathologica. Supplementum · doi:10.1007/978-3-642-81553-9_8 · Cited by 66
Folic Acid Enhances Early Functional Recovery in a Piglet Model of Pediatric Head Injury
Naim, M., Friess, S., Smith, C. M., Ralston, J., Ryall, K., Helfaer, M., & Margulies, S. (2011) · Developmental Neuroscience · doi:10.1159/000322448 · Cited by 64
Self-citationInjury tolerances for oblique impact helmet testing
Aare, M., Kleiven, S., & Halldin, P. (2004) · doi:10.1533/ijcr.2004.0268 · Cited by 59 · cited 1×
“head (linear and rotational accelerations), and the predicted diffuse strain fields in the brain [156, 157].”
Margulies, S. S., Kilbaugh, T. J., Sullivan, S., Smith, C., PROPERT, K. J., Byro, M., Saliga, K., Costine, B. A., & Duhaime, A. (2015) · Brain Pathology · doi:10.1111/bpa.12247 · Cited by 58 · see citing works
Self-citationElastomechanical characterization of brain tissues.
Sahay, K., Mehrotra, R., Sachdeva, U., & Banerji, A. (1992) · Journal of Biomechanics · doi:10.1016/0021-9290(92)90029-z · Cited by 56 · cited 1×
“Moreover, in closed-head diffuse brain injury, the dominant mode of brain tissue deformation is shear strain, owing to the shear modulus being at least several orders of magnitude lower than the bulk modulus of brain tissue [56, 70, 80, 81].”
Physiological and Pathological Responses to Head Rotations in Toddler Piglets
Ibrahim, N. G., Ralston, J., Smith, C. M., & Margulies, S. (2010) · Journal of Neurotrauma · doi:10.1089/neu.2009.1212 · Cited by 53 · see citing works
Self-citationMechanical trauma induces immediate changes in neuronal network activity
Prado, G., Ross, J., DeWeerth, S., & LaPlaca, M. (2005) · Journal of Neural Engineering · doi:10.1088/1741-2560/2/4/011 · Cited by 51 · see citing works
Ocular hemorrhages in neonatal porcine eyes from single, rapid rotational events.
Coats, B., Binenbaum, G., Peiffer, R., Forbes, B., & Margulies, S. (2010) · Investigative Ophthalmology and Visual Science · doi:10.1167/iovs.10-5211 · Cited by 47
Self-citationDenny-Brown, D., & Russell, W. (1941) · Proceedings of the Royal Society of Medicine · doi:10.1177/003591574103401102 · Cited by 47
Meng, X., Browne, K., Huang, S.-M., Mietus, C., Cullen, D. K., Tofighi, M., & Rosen, A. (2013) · IEEE transactions on microwave theory and techniques · doi:10.1109/tmtt.2012.2224361 · Cited by 44 · see citing works
Self-citationFriess, S., Ralston, J., Eucker, S., Helfaer, M., Smith, C. M., & Margulies, S. (2011) · Neurosurgery · doi:10.1227/neu.0b013e3182284aa1 · Cited by 41
Self-citationWeeks, D., Sullivan, S., Kilbaugh, T., Smith, C. M., & Margulies, S. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2013.3113 · Cited by 39
Self-citationLetcher, F., Corrao, P., & Ommaya, A. (1973) · Journal of Neurosurgery · doi:10.3171/jns.1973.39.2.0167 · Cited by 33
Monte, V. D., Geffen, G., & Massavelli, B. (2006) · Brain Injury · doi:10.1080/02699050601082073 · Cited by 30 · see citing works
Improved Behavior, Motor, and Cognition Assessments in Neonatal Piglets
Sullivan, S., Friess, S., Ralston, J., Smith, C. M., Propert, K., Rapp, P., & Margulies, S. (2013) · Journal of Neurotrauma · doi:10.1089/neu.2013.2913 · Cited by 29 · see citing works
Self-citationIn situ deformations in the immature brain during rapid rotations.
Ibrahim, N. G., Natesh, R., Szczesny, S. E., Ryall, K., Eucker, S., Coats, B., & Margulies, S. (2010) · Journal of Biomechanical Engineering · doi:10.1115/1.4000956 · Cited by 27 · cited 2×
“To further establish links between macro- and micro-biomechanical features as well as to advance scaling to human injuries, the HYGE device has been used to subject physical models of the skull brain structures to identical loading conditions used to produce specific brain injuries in animals [63, 65, 66, 104, 126].”
Self-citationFriess, S., Naim, M. Y., Kilbaugh, T., Ralston, J., & Margulies, S. S. (2012) · Laboratory Animals. Journal of the Laboratory Animal Science Association · doi:10.1258/la.2011.011084 · Cited by 25 · see citing works
Self-citationZhang, J., Groff, R., Chen, X.-H., Browne, K., Huang, J. H., Schwartz, E., Meaney, D., Johnson, V., Stein, S., Røjkjaer, R., et al. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2007.12.019 · Cited by 23 · see citing works
Self-citationFriess, S., Bruins, B., Kilbaugh, T., Smith, C. M., & Margulies, S. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2014.3468 · Cited by 22 · see citing works
Self-citationFriess, S., Smith, C. M., Kilbaugh, T., Frangos, S., Ralston, J., Helfaer, M., & Margulies, S. (2012) · Critical Care Medicine · doi:10.1097/ccm.0b013e31825333e6 · Cited by 20
Self-citationPredicting Unconsciousness from a Pediatric Brain Injury Threshold
Zhu, Q.-L., Prange, M., & Margulies, S. (2006) · Developmental Neuroscience · doi:10.1159/000094165 · Cited by 20
Self-citationNoninvasive Metrics for Identification of Brain Injury Deficits in Piglets
Jaber, S. M., Sullivan, S., & Margulies, S. (2015) · Developmental Neuropsychology · doi:10.1080/87565641.2014.969733 · Cited by 16 · see citing works
Self-citationDynamic study of wireless intracranial pressure monitoring of rotational head injury in swine model
Meng, X., Browne, K., Huang, S.-M., Cullen, D. K., Tofighi, M., & Rosen, A. (2012) · doi:10.1049/el.2012.0281 · Cited by 15
Self-citationCarotid Artery Blood Flow Decreases after Rapid Head Rotation in Piglets
Clevenger, A., Kilbaugh, T., & Margulies, S. (2015) · Journal of Neurotrauma · doi:10.1089/neu.2014.3570 · Cited by 14
Self-citationCoats, B., Eucker, S., Sullivan, S., & Margulies, S. S. (2012) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2011.12.009 · Cited by 13
Self-citation
Flagged first, then by citations
24 of the 166 references couldn’t be matched to a known paper.
Research works printed but not linked: 19
- [6]Thurman DJ Alverson C Dunn KA Guerrero J Sniezek JE 1999 Traumatic brain injury in the United States: a public health perspective J Head Trauma Rehabil 14 602 615 10671706
- [7]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 24199265
- [10]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 21976115
- [12]Hoge CW McGurk D Thomas JL Cox AL Engel CC Castro CA 2008 Mild traumatic brain injury in U.S. Soldiers returning from Iraq N Engl J Med 358 453 463 18234750
- [21]McIntosh TK Smith DH Meaney DF Kotapka MJ Gennarelli TA Graham DI 1996 Neuropathological sequelae of traumatic brain injury: relationship to neuro-chemical and biomechanical mechanisms Lab Invest 74 315 342 8780153
- [23]Gennarelli TA 1993 Mechanisms of brain injury J Emerg Med 11 Suppl 1 5 11 8445204
- [25]McIntosh TK Juhler M Raghupathi R Saatman KE Smith DH 1999 Secondary brain injury: neurochemical and cellular mediators Marion W Traumatic brain injury Thieme Medical Publishers New York, NY 39 54
- [37]Mouzon B Bachmeier C Ferro A Ojo JO Crynen G Acker C Davies P Mullan M Stewart W Crawford F 2013 Chronic neuropathological and neurobehavioral changes in a repetitive mTBI model Ann Neurol 75 2 241 254 24243523
- [38]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 19535999 PMC2945234
- [39]McIntosh TK 1994 Neurochemical sequelae of traumatic brain injury: therapeutic implications Cerebrovasc Brain Metab Rev 6 109 162 7915532
- [42]Ryan LM Warden DL 2003 Post concussion syndrome Int Rev Psychiatry 15 310 316 15276952
- [58]Yarnell P Ommaya AK 1969 Experimental cerebral concussion in the rhesus monkey Bull N Y Acad Med 45 39 45 4977441 PMC1750322
- [61]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 797 803
- [81]Kleiven S 2013 Why most traumatic brain injuries are not caused by linear acceleration but skull fractures are Front Bioeng Biotechnol 1 15 25022321 PMC4090913
- [89]Graham DI Adams JH Gennarelli TA 1988 Mechanisms of non-penetrating head injury Prog Clin Biol Res 234 159 168 3289020
- [125]Thibault LE Gennarelli TA 1989 Biomechanics of diffuse brain injuries Proceedings of the 10th international technical conference on experimental safety vehicles DOT, NHTSA
- [134]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 PMC5510797 28298170
- [138]McGowan JC McCormack TM Grossman RI Mendonca R Chen XH Berlin JA Meaney DF Xu BN Cecil KM McIntosh TK Smith DH 1999 Diffuse axonal pathology detected with magnetization transfer imaging following brain injury in the pig Magn Reson Med 41 727 733 10332848
- [147]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
Cited by
Sorted by citations
Mechanical disruption of the blood–brain barrier following experimental concussion
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 156 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
Mechanosensation in traumatic brain injury
Keating, C. E., & Cullen, D. K. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105210 · Cited by 103 · see citing works
“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
Wofford, K. L., Loane, D. J., & Cullen, D. K. (2019) · Neural Regeneration Research · doi:10.4103/1673-5374.255958 · Cited by 103 · see citing works
“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 · see citing works
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 · see citing works
“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 77 · see citing works
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 · see citing works
“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 65 · see citing works
The Use of Pigs as a Translational Model for Studying Neurodegenerative Diseases
Hoffe, B., & Holahan, M. R. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00838 · Cited by 71 · see citing works
McNamara, E. H., Grillakis, A., Tucker, L. B., & McCabe, J. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113409 · Cited by 61 · see citing works
“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., Mietus, C., Brown, D. P., Wofford, K. L., Smith, D. H., Grady, M., et al. (2017) · Journal of Neurotrauma · doi:10.1089/neu.2016.4848 · Cited by 51 · see citing works
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 · see citing works
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 57 · see citing works
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 58 · see citing works
“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 · see citing works
“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 · see citing works
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 47 · see citing works
Self-citationHajiaghamemar, M., Seidi, M., Oeur, A., & Margulies, S. S. (2019) · Experimental Neurology · doi:10.1016/j.expneurol.2019.04.019 · Cited by 37 · see citing works
“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 · see citing works
Self-citationElastic behavior of brain simulants in comparison to porcine brain at different loading velocities.
Falland-Cheung, L., Scholze, M., Hammer, N., Waddell, J. N., Tong, D. C., & Brunton, P. (2018) · Journal of The Mechanical Behavior of Biomedical Materials · doi:10.1016/j.jmbbm.2017.10.026 · Cited by 30
Grovola, M. R., von Reyn, C. R., Loane, D. J., & Cullen, D. K. (2023) · Journal of Neuroinflammation · doi:10.1186/s12974-023-02730-z · Cited by 32 · see citing works
“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 24 · see citing works
“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
Hoogenboom, W. S., Rubin, T. G., Ye, K. Q., Cui, M., Branch, K. C., Liu, J., Branch, C. A., & Lipton, M. L. (2019) · Journal of Experimental Neuroscience · doi:10.1177/1179069519858627 · Cited by 32 · see citing works
Modulation of Macrophage Phenotype via Phagocytosis of Drug-Loaded Microparticles
Wofford, K. L., Cullen, D. K., & Spiller, K. (2019) · Journal of Biomedical Materials Research. Part A · doi:10.1002/jbm.a.36617 · Cited by 24 · see citing works
“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 · see citing works
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 19 · see citing works
“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 · see citing works
“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 · see citing works
“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 28 · see citing works
Bedside to bench: the outlook for psychedelic research
Acero, V. P., Cribas, E. S., Browne, K. D., Rivellini, O. M., Burrell, J. C., O’Donnell, J. C., Das, S., & Cullen, D. K. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1240295 · Cited by 22 · see citing works
“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).”
BackgroundMethodSelf-citationElectrophysiological Signature Reveals Laminar Structure of the Porcine Hippocampus
Ulyanova, A. V., Koch, P. F., Cottone, C., Grovola, M. R., Adam, C. D., Browne, K. D., Weber, M. T., Russo, R. J., Gagnon, K. G., Smith, D. H., et al. (2018) · eNeuro · doi:10.1523/eneuro.0102-18.2018 · Cited by 19 · see citing works
“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 · see citing works
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 · see citing works
“are necessary to better understand the mechanisms of auditory dysfunction.(58) Our understanding of inner ear pathologies has grown and now”
BackgroundA systematic review of large animal models of combined traumatic brain injury and hemorrhagic shock
Mayer, A. R., Dodd, A. B., Vermillion, M. S., Stephenson, D. D., Chaudry, I. H., Bragin, D. E., Gigliotti, A. P., Dodd, R. J., Wasserott, B. C., Shukla, P., et al. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.06.024 · Cited by 23 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
“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”
BackgroundMethodSelf-citationThe role of cervical muscles in mitigating concussion.
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 · see citing works
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 · see citing works
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 · see citing works
“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 · see citing works
Translational models of mild traumatic brain injury tissue biomechanics
Zhan, X.-H., Oeur, A., Liu, Y.-Z., Zeineh, M., Grant, G., Margulies, S., & Camarillo, D. B. (2022) · Current Opinion in Biomedical Engineering · doi:10.1016/j.cobme.2022.100422 · Cited by 15
Self-citationArmstead, W., & Vavilala, M. (2020) · Journal of Neurotrauma · doi:10.1089/neu.2018.6119 · Cited by 15 · see citing works
“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 · see citing works
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 · see citing works
“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 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 14 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
“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 · see citing works
“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 · see citing works
Song, J. Y., Fleysher, R., Ye, K., Kim, M., Zimmerman, M. E., Lipton, R., & Lipton, M. L. (2025) · NeuroImage · doi:10.1016/j.neuroimage.2025.121019 · Cited by 10 · see citing works
“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 · see citing works
“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 · see citing works
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 · see citing works
“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., Jaffee, M. S., & Bauer, R. (2018) · Journal of the American Medical Association (JAMA) · doi:10.1001/jama.2017.20885 · Cited by 9 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
“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 · see citing works
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 · see citing works
“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 · see citing works
“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 · see citing works
Zhao, X., & He, Z. (2025) · Neuroscience Research · doi:10.1016/j.neures.2025.104979 · Cited by 5 · see citing works
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., Johnson, V., Cullen, D. K., et al. (2023) · bioRxiv · doi:10.1038/s42003-023-05491-w · Cited by 5 · see citing works
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 · see citing works
“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 · see citing works
Porcine Astrocytes and Their Relevance for Translational Neurotrauma Research
Purvis, E. M., Fedorczak, N., Prah, A., Han, D., & O'Donnell, J. C. (2023) · Biomedicines · doi:10.3390/biomedicines11092388 · Cited by 4 · see citing works
“…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 · see citing works
“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 · see citing works
“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 · see citing works
“…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. (2025) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-25-00902 · Cited by 3
“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 · see citing works
“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
- 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
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › 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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