Adaptation of the fluid percussion injury model to the mouse
Abstract
Fluid percussion injury (FPI) is a well-characterized experimental model of traumatic brain injury (TBI) in the rat. Many pathophysiologic consequences and mechanisms of recovery after TBI rely on neurochemical pathways that can be examined in genetically altered mice. Therefore, FPI applied to mice may be a useful experimental tool to investigate TBI at the molecular level. In the present study, we establish FPI as a viable model of TBI in the mouse by characterizing acute neurological, histopathological, and behavioral changes. Right-sided parasagittal FPI or sham treatment was administered in male C57BL/6 mice. Acute neurological evaluation revealed righting reflexes in the injured animals (p < 0.001). Deficits in spatial learning and memory were observed in the Morris water maze (MWM) 5 and 6 days after injury. A novel MWM data analysis protocol is described. The injured group (n = 18) demonstrated impaired performance in the MWM during acquisition (p < 0.05) and probe trials (p < 0.025) compared to sham animals (n = 16). At 7 days postinjury, glial fibrillary acidic protein immunohistochemistry revealed intense cortical, callosal, and hippocampal gliosis. The modified Gallyas silver degeneration stain consistently labeled cell bodies and terminals throughout the ipsilateral cortex, axons in the gray matter-white matter interface above the corpus callosum and within the corpus callosum bilaterally, and terminals and fibers in the thalamus bilaterally. Additionally, the mo…
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Many biological pathways are disrupted by experimental TBI resulting in progressive neurodegeneration including atrophy, neuronal loss, and axonal degeneration which are often associated with neuroinflammation including macrophage reactivity.
“Many biological pathways are disrupted by experimental TBI resulting in progressive neurodegeneration including atrophy, neuronal loss, and axonal degeneration which are often associated with neuroinflammation including macrophage reactivity (82–85).”
From The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease (2018) · cites this paper as [82]
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InfluentialMathematical Models of Blast-Induced TBI: Current Status, Challenges, and Prospects
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“…a model of TBI that elicits hippocampal-dependent memory impairments, fluid-percussion brain injury (FPI) (Lyeth et al, 1990; Bramlett et al, 1997a; Carbonell et al, 1998; Sanders et al, 1999; Griesbach et al, 2004b), we determined if calcium/ calmodulin-dependent protein kinases known to be…”
BackgroundModels of Traumatic Brain Injury
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“Common methods used to investigate DBI pathologies include weight drop (Marmarou et al., 1994; Lammie et al., 1999), controlled cortical impact (Lighthall, 1988), projectile impact (Morehead et al., 1994; Cernak et al., 2004), and fluid percussion (Dixon et al., 1987; Carbonell et al., 1998).”
Response of the Contralateral Hippocampus to Lateral Fluid Percussion Brain Injury
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Self-citationShultz, S. R., Tan, X. L., Wright, D. K., Liu, S. J., Semple, B. D., Johnston, L. A., Jones, N. C., Cook, A. D., Hamilton, J. A., & O'Brien, T. J. (2014) · Journal of Neurotrauma · doi:10.1089/neu.2013.3106 · Cited by 66 · see citing works
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BackgroundPotentials of endogenous neural stem cells in cortical repair
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“These include controlled cortical impact (CCI) (Ramaswamy et al., 2005); fluid-percussion injury (FPI) (Carbonell et al., 1998; Chirumamilla et al., 2002; Chen et al., 2003); aspiration lesions (Szele and Chesselet, 1996) and focal acute injury (FAI) (Blizzard et al., 2011).”
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“Firstly, FPI leads to diffuse brain injury that includes hemorrhagic contusions and reaches distant brain regions relative to the primary impact site [56-58].”
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“…this model injures all neuronal subcellular compartments yet enables selective analysis of specific compartments, and mimics injury to gray matter populations and their connecting white matter tracts, as experienced in the brain (Carbonell et al. 1998; Smith et al. 1999; Lusardi et al. 2004).”
Rodent Models of Traumatic Brain Injury: Methods and Challenges
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“Importantly, based on a significant body of work over the past 3 decades [47], this fluid pressure pulse has previously been shown to generate a mild brain injury, given the short latency to righting reflex [48, 49] and lack significant cell death and cavitation of the ventricles [50].”
BackgroundModels of Mild Traumatic Brain Injury
Petraglia, A. L., Dashnaw, M. L., Turner, R. C., & Bailes, J. E. (2014) · Neurosurgery · doi:10.1227/neu.0000000000000472 · Cited by 63 · see citing works
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MethodSelf-citationExperimental Trauma Models: An Update
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“6 atm [52] (b) inadequate trauma <2 cm [60]”
BackgroundMethodResultInfluentialRoadmap 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
SDF-1α induces angiogenesis after traumatic brain injury.
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Historical Review of the Fluid-Percussion TBI Model
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“The surgical difficulty in drilling the fragile cranium with more flexible cranial sutures posed challenges that were met with alterations in the number and placement of anchor screws as well as the use of a gel form of cyanoacrylate adhesive to secure the injury cannula (20).”
BackgroundDiminished amygdala activation and behavioral threat response following traumatic brain injury
Palmer, C. P., Metheny, H. E., Elkind, J. A., & Cohen, A. S. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.01.004 · Cited by 39 · see citing works
“LFPI is a well-establishedmodel ofmild tomoderate traumatic brain injury that mimics many aspects of human TBI pathology and symptomatology (Carbonell et al., 1998; Thompson et al., 2005; Xiong et al., 2013).”
Brain Injury in the Context of Tauopathies
Abisambra, J. F., & Scheff, S. W. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131019 · Cited by 38 · see citing works
“Importantly, the lateral FP technique was also adapted for mice [140–142], which makes it a useful tool for studying changes in transgenic animals.”
MethodNeuroanatomical correlation of behavioral deficits in the CCI model of TBI
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Shishido, H., Kishimoto, Y., Kawai, N., Toyota, Y., Ueno, M., Kubota, T., Kirino, Y., & Tamiya, T. (2016) · Neuroscience Letters · doi:10.1016/j.neulet.2016.06.066 · Cited by 38 · see citing works
Animal Models of Posttraumatic Seizures and Epilepsy
Glushakov, A. V., Glushakova, O. Y., Doré, S., Carney, P. R., & Hayes, R. L. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3816-2_27 · Cited by 39 · see citing works
Blood–brainbarrier disruption dictates nanoparticle accumulation following experimental brain injury
Bharadwaj, V. N., Rowe, R. K., Harrison, J., Wu, C., Anderson, T. R., Lifshitz, J., Adelson, P., Kodibagkar, V., & Stabenfeldt, S. (2018) · Nanomedicine: Nanotechnology, Biology and Medicine · doi:10.1016/j.nano.2018.06.004 · Cited by 34 · see citing works
Molecular correlates of age-specific responses to traumatic brain injury in mice.
Shah, S. A., Prough, D., Garcia, J. M., Dewitt, D., & Hellmich, H. L. (2006) · Experimental Gerontology · doi:10.1016/j.exger.2006.07.006 · Cited by 34 · see citing works
Animal Models of Traumatically-Induced Dementia
Slemmer, J., Hossain, M. Z., & Weber, J. (2011) · Neuromethods · doi:10.1007/978-1-60761-898-0_32 · Cited by 34 · see citing works
Effects of concussion on the blood–brain barrier in humans and rodents
Sahyouni, R., Gutierrez, P., Gold, E. M., Robertson, R. T., & Cummings, B. J. (2017) · Journal of Concussion · doi:10.1177/2059700216684518 · Cited by 32 · see citing works
A Detrimental Role for Nitric Oxide Synthase‐2 in the Pathology Resulting from Acute Cerebral Injury
Jones, N., Constantin, D., Gibson, C., Prior, M., Morris, P., Marsden, C., & Murphy, S. (2004) · Journal of Neuropathology and Experimental Neurology · doi:10.1093/jnen/63.7.708 · Cited by 33
Vishwanath, M., Jafarlou, S., Shin, I., Lim, M., Dutt, N., Rahmani, A.-M., & Cao, H. (2020) · Italian National Conference on Sensors · doi:10.3390/s20072027 · Cited by 30 · see citing works
“This has previously been shown by various research groups to induce mTBI [14,15].”
Midline (Central) Fluid Percussion Model of Traumatic Brain Injury.
Rowe, R. K., Griffiths, D. R., & Lifshitz, J. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-3816-2_13 · Cited by 30 · see citing works
Witgen, B., Lifshitz, J., & Grady, M. (2006) · Journal of Neurotrauma · doi:10.1089/neu.2006.23.1320 · Cited by 29 · see citing works
“In the mouse, this experimental model of injury produces memory dysfunction and anatomical alterations, notably in the hippocampus, in a reproducible manner (Carbonell et al., 1998; Witgen et al., 2005).”
Self-citationShishido, H., Ueno, M., Sato, K., Matsumura, M., Toyota, Y., Kirino, Y., Tamiya, T., Kawai, N., & Kishimoto, Y. (2019) · Behavioural Neurology · doi:10.1155/2019/3248519 · Cited by 28 · see citing works
A Novel Mouse Model of Penetrating Brain Injury
Cernak, I., Wing, I., Davidsson, J., & Plantman, S. (2014) · Frontiers in Neurology · doi:10.3389/fneur.2014.00209 · Cited by 28 · see citing works
“BODYWEIGHT Loss of bodyweight has been reported in mice after CCI (40), fluid-percussion (29), and blast-induced TBI (27) models.”
BackgroundMethodCarlson, S. W., Henchir, J. J., & Dixon, C. (2017) · Frontiers in Neurology · doi:10.3389/fneur.2017.00532 · Cited by 25 · see citing works
Ekmark-Lewén, S., Flygt, J., Fridgeirsdottir, G. A., Kiwanuka, O., Hånell, A., Meyerson, B., Mir, A., Gram, H., Lewén, A., Clausen, F., et al. (2016) · European Journal of Neuroscience · doi:10.1111/ejn.13190 · Cited by 25 · see citing works
“Like the lateral fluid percussion model (Carbonell et al., 1998), the central fluid percussion injury (cFPI) model commonly used in rats has been adapted to the mouse (Greer et al., 2011; Ekmark-Lew en et al., 2013).”
MethodCarbonell, W. S., & Grady, M. S. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb08005.x · Cited by 25 · see citing works
Self-citationExperimental Models of Head Trauma
Leker, R. R., Shohami, E., & Constantini, S. (2002) · Springer eBooks · doi:10.1007/978-3-7091-6743-4_9 · Cited by 26 · see citing works
Midline (central) fluid percussion model of traumatic brain injury in pediatric and adolescent rats.
Rowe, R. K., Harrison, J., Ellis, T., Adelson, P., & Lifshitz, J. (2018) · Journal of Neurosurgery: Pediatrics · doi:10.3171/2018.1.peds17449 · Cited by 24 · see citing works
Li, S.-H., Kuroiwa, T., Katsumata, N., Ishibashi, S., Sun, L.-Y., Endo, S., & Ohno, K. (2006) · Journal of Neuroscience Research · doi:10.1002/jnr.20720 · Cited by 22
“Experimental studies with fluid percussion injury have employed a variety of species (Lindgren and Rinder, 1969; Sullivan et al., 1976; Millen et al., 1985; Dixon et al., 1987; Carbonell et al., 1998).”
BackgroundAnimal Models of Movement Disorders
Lane, E., & Dunnett, S. (2012) · Neuromethods · doi:10.1007/978-1-61779-298-4 · Cited by 22
“For example, regional striatal lesions have demonstrated the differential effects of the lateral and medial striatal contribution to motor functions (47).”
BackgroundInfluentialA new multiple trauma model of the mouse
Fitschen-Oestern, S., Lippross, S., Klueter, T., Weuster, M., Varoga, D., Tohidnezhad, M., Pufe, T., Rose-John, S., Andruszkow, H., Hildebrand, F., et al. (2017) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-017-1813-9 · Cited by 21 · see citing works
Modelos experimentales de traumatismo craneoencefálico
Prieto, R., Gutiérrez-González, R., Pascual, J., Roda, J., Cerdán, S., Matías-Guíu, J., & Barcia, J. (2009) · Neurocirugía · doi:10.4321/s1130-14732009000300001 · Cited by 20 · see citing works
Schurman, L. D., Smith, T. L., Morales, A. J., Lee, N. N., Reeves, T. M., Phillips, L., & Lichtman, A. (2017) · Neuroscience Letters · doi:10.1016/j.neulet.2017.05.032 · Cited by 19 · see citing works
“MWM Fixed Platform acquisition deficits [5,11] have been shown in right hemisphere injury, though contrary to the present findings, others have noted acquisition deficits also from left lateral injuries [9,10].”
BackgroundResultSeverity assessment and scoring for neurosurgical models in rodents
Pinkernell, S., Becker, K., & Lindauer, U. (2016) · Laboratory Animals · doi:10.1177/0023677216675010 · Cited by 21 · see citing works
“Mortality in fluid percussion injury (FPI) models depends strongly on the size of the pressure pulse, with mild to moderately severe impact resulting in mortality rates of 10–22% in rats(17) and zero mortality in mice.(18) In the ‘Marmarou’ (weight drop impact acceleration [WDIA]) model, the originally described morta…”
BackgroundKazanis, I. (2005) · Brain research. Brain research reviews · doi:10.1016/j.brainresrev.2005.09.003 · Cited by 19
Injury Models of the Central Nervous System
Kobeissy, F., Dixon, C., Hayes, R., & Mondello, S. (2016) · Methods in Molecular Biology · doi:10.1007/978-1-4939-3816-2 · Cited by 19
Selvakumar, G. P., Ahmed, M. E., Iyer, S. S., Thangavel, R., Kempuraj, D., Raikwar, S. P., Bazley, K., Wu, K., Khan, A. C., Kukulka, K., et al. (2020) · Experimental Neurobiology · doi:10.5607/en20017 · Cited by 18 · see citing works
“In mouse models, TBI mice exhibit decreased motor and cognitive behavior outcomes compared with control mice [89-93].”
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“Over the last decade, the CCI model and the fluid percussion injury have been the two widely used TBI models in the laboratory [15,28,29].”
MethodFerreira, A. P. O., Rodrigues, F., Della-Pace, I. D., Mota, B. C., Oliveira, S. M., Gewehr, C. D. C. V., Bobinski, F., de Oliveira, C. V., Brum, J., Oliveira, M. S., et al. (2014) · Psychopharmacology · doi:10.1007/s00213-013-3336-x · Cited by 18 · see citing works
“HOE-140 and DAL-Bk had no effect on neuromotor deficit induced by mLFPI Figures 3 and 4 demonstrate the effect of B2R antagonist (HOE-140; 1 or 10 nmol/kg) or B1R antagonist (desArg9-[Leu8]-bradykinin (DAL-Bk; 1 or 10 nmol/kg) on neuromotor behavior after mLFPI.”
BackgroundMethodInfluentialChuckowree, J., Zhu, Z., Brizuela, M., Lee, K.-M., Blizzard, C. A., & Dickson, T. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00223 · Cited by 17 · see citing works
Rowe, R. K., Griffiths, D. R., & Lifshitz, J. (2009) · Springer Series in Translational Stroke Research · doi:10.1007/978-1-60327-185-1_32 · Cited by 17 · see citing works
Laurer, H., Meaney, D., Margulies, S., & McIntosh, T. (2002) · Elsevier eBooks · doi:10.1016/b0-12-227210-2/00211-9 · 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
Taiwo, O. B., Kovács, K., & Larson, A. (2005) · Brain Research · doi:10.1016/j.brainres.2005.07.022 · Cited by 16 · see citing works
Animal Models of Traumatic Brain Injury and Their Relevance in Clinical Settings
Chauhan, P., Yadav, N. S., Wadhwa, K., Ganesan, S., Walia, C., Rathore, G., Singh, G., Abomughaid, M. M., Ahlawat, A., Alexiou, A. T., et al. (2025) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.70362 · Cited by 13 · see citing works
“…a i n c o n c u ss i o n , a n d c o n t u s i o n , i n c l u d i n g s p o r t s - r e l a t e d T B I [ 140 ] • H i g h m o r t a l i t y [ 141 , 142 ] CC I m o d e l • L o w m o r t a l i t y a n d s i m p l e p r e p a r a t i o n [ 143 ] • C a u s e r e p r o d u c i b l e f o c a l b r a i…”
- Authors
- CARBONELL, W. S., MARIS, D. O., McCALL, T., & GRADY, M. S.
- Affiliations
- University of Washington (US)
- ORCID
- CARBONELL, W. SHAWN
- Venue
- Journal of Neurotrauma
- Publisher
- SAGE Publications
- Published
- 1998-03
- Volume
- 15
- Issue
- 3
- Pages
- 217-229
- ISSN
- 0897-7151 (ISSN-L)
- 1557-9042
- OpenAlex
- W1978835755
- Cited by
- 157
- References
- 0
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 2 · 2021: 6 · 2020: 7 · 2019: 10 · 2018: 10 · 2017: 10 · 2016: 13 · 2015: 5 · 2014: 9 · 2013: 11 · 2012: 4
- FWCI
- 1.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurotrauma (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Washington
- National Institutes of Health (5p50ns030305-05, 5r01ns033107-03)
- National Institute of Neurological Disorders and Stroke (NS-30305, NS33107)
- Topics
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Automotive and Human Injury Biomechanics
- Keywords
- fluid percussion injury, traumatic brain injury, mouse model, spatial learning and memory, Morris water maze, gliosis, glial fibrillary acidic protein, corpus callosum, thalamus, righting reflex, behavioral deficits
- MeSH terms
- Animals, Brain Injuries, Postural Balance, Glial Fibrillary Acidic Protein, Gliosis, Male, Mice, Inbred C57BL, Neuroglia, Neurons, Silver Staining, Maze Learning, Mice, Rats
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