Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Protocol
  • Published:

Fluid-percussion–induced traumatic brain injury model in rats

Nature Protocols volume 5, pages 1552–1563 (2010)Cite this article

Subjects

Abstract

Traumatic brain injury (TBI) is a major cause of mortality and morbidity. Various attempts have been made to replicate clinical TBI using animal models. The fluid-percussion model (FP) is one of the oldest and most commonly used models of experimentally induced TBI. Both central (CFP) and lateral (LFP) variations of the model have been used. Developed initially for use in larger species, the standard FP device was adapted more than 20 years ago to induce consistent degrees of brain injury in rodents. Recently, we developed a microprocessor-controlled, pneumatically driven instrument, micro-FP (MFP), to address operational concerns associated with the use of the standard FP device in rodents. We have characterized the MFP model with regard to injury severity according to behavioral and histological outcomes. In this protocol, we review the FP models and detail surgical procedures for LFP. The surgery involves tracheal intubation, craniotomy and fixation of Luer fittings, and induction of injury. The surgical procedure can be performed within 45–50 min.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Classical model of lateral fluid percussion (LFP; Amscien Instruments).
Figure 2: MFP device.
Figure 3: The impactor assembly of the MFP device.
Figure 4: The initiator assembly of the MFP device.
Figure 5: Mortality rates (%) associated with different pressures (atm) of injury.
Figure 6: Assessment of composite neurological scores.
Figure 7: Assessment of cognitive performance.
Figure 8: Assessment of lesion volumes by histology.
Figure 9: Determination of neuronal cell loss in CA3 subregion of the hippocampus.

Similar content being viewed by others

References

  1. Centers for Disease Control and Prevention. Get the Stats on Traumatic Brain Injury in the United States. Centers for Disease Control and Prevention, Atlanta, Georgia, USA. <http://www.cdc.gov/traumaticbraininjury/pdf/BlueBook_factsheet-a.pdf> (2010).

  2. French, L.M. & Parkinson, G.W. Assessing and treating veterans with traumatic brain injury. J. Clin. Psychol. 64, 1004–1013 (2008).

    Article  PubMed  Google Scholar 

  3. Hoge, C.W. Mild traumatic brain injury in U.S. soldiers returning from Iraq. N. Engl. J. Med. 358, 453–463 (2008).

    Article  CAS  PubMed  Google Scholar 

  4. Ellemberg, D., Henry, L.C., Macciocchi, S.N., Guskiewicz, K.M. & Broglio, S.P. Advances in sport concussion assessment: from behavioral to brain imaging measures. J. Neurotrauma 26, 2365–2382 (2009).

    Article  PubMed  Google Scholar 

  5. Denny-Brown, D. & Russell, W.R. Experimental cerebral concussion. Brain 64, 93–164 (1941).

    Article  Google Scholar 

  6. Cernak, I. Animal models of head trauma. NeuroRx. 2, 410–422 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  7. David, S. & Aguayo, A.J. Axonal regeneration after crush injury of rat central nervous system fibres innervating peripheral nerve grafts. J. Neurocytol. 14, 1–12 (1985).

    Article  CAS  PubMed  Google Scholar 

  8. Park, H.J. et al. Redistribution of facial nerve motor neurons after recovery from nerve crushing injury in the gerbil. Acta Otolaryngol. 115, 273–275 (1995).

    Article  CAS  PubMed  Google Scholar 

  9. Finnie, J.W. Pathology of experimental traumatic craniocerebral missile injury. J. Comp. Pathol. 108, 93–101 (1993).

    Article  CAS  PubMed  Google Scholar 

  10. Carey, M.E. Experimental missile wounding of the brain. Neurosurg. Clin. N. Am. 6, 629–642 (1995).

    Article  CAS  PubMed  Google Scholar 

  11. Goldman, H. et al. Cerebrovascular changes in a rat model of moderate closed-head injury. J. Neurotrauma 8, 129–144 (1991).

    Article  CAS  PubMed  Google Scholar 

  12. Marmarou, A. et al. A new model of diffuse brain injury in rats. Part I: pathophysiology and biomechanics. J. Neurosurg. 80, 291–330 (1994).

    Article  CAS  PubMed  Google Scholar 

  13. Foda, M.A. & Marmarou, A. A new model of diffuse brain injury in rats. Part II: morphological characterization. J. Neurosurg. 80, 301–313 (1994).

    Article  CAS  PubMed  Google Scholar 

  14. Cernak, I. et al. The pathobiology of moderate diffuse traumatic brain injury as identified using a new experimental model of injury in rats. Neurobiol. Dis. 17, 29–43 (2004).

    Article  CAS  PubMed  Google Scholar 

  15. Finnie, J.W. & Blumbergs, P.C. Traumatic brain injury. Vet. Pathol. 39, 679–689 (2002).

    Article  CAS  PubMed  Google Scholar 

  16. Blumbergs, P.C. et al. Diffuse axonal injury in head trauma. J. Neurol. Neurosurg. Psychiatry 52, 838–841 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Finnie, J.W. et al. Traumatic axonal injury in lambs: a model for paediatric axonal damage. J. Clin. Neurosci. 6, 38–42 (1999).

    Article  CAS  PubMed  Google Scholar 

  18. Betz, A.L. et al. Brain edema: a classification based on blood–brain barrier integrity. Cerebrovasc. Brain Metab. Rev. 1, 133–154 (1989).

    CAS  PubMed  Google Scholar 

  19. Smith, D.H. et al. Progressive atrophy and neuron death for one year following brain trauma in the rat. J. Neurotrauma 14, 715–727 (1997).

    Article  CAS  PubMed  Google Scholar 

  20. DeKosky, S.T. et al. Secondary injury after head trauma: subacute and long-term mechanisms. Semin. Clin. Neuropsychiatry 3, 176–185 (1998).

    CAS  PubMed  Google Scholar 

  21. Hamm, R.J. Neurobehavioral assessment of outcome following traumatic brain injury in rats: an evaluation of selected measures. J. Neurotrauma 18, 1207–1216 (2001).

    Article  CAS  PubMed  Google Scholar 

  22. Meythaler, J.M. et al. Current concepts: diffuse axonal injury-associated traumatic brain injury. Arch. Phys. Med. Rehabil. 82, 1461–1471 (2001).

    Article  CAS  PubMed  Google Scholar 

  23. Marguiles, S.S. & Thibault, L.E. An analytical model of traumatic diffuse brain injury. J. Biomech. Eng. 111, 241–249 (1989).

    Article  Google Scholar 

  24. Cernak, I. et al. Blast injury from explosives munitions. J. Trauma 47, 96–103 (1999).

    Article  CAS  PubMed  Google Scholar 

  25. Cernak, I. et al. Ultrastructural and functional characteristics of blast injury-induced neurotrauma. J. Trauma 50, 695–706 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. Saljo, A. et al. Blast exposure causes redistribution of phosphorylated neurofilament subunits in neurons of the adult rat brain. J. Neurotrauma 17, 719–726 (2000).

    Article  CAS  PubMed  Google Scholar 

  27. Millen, J.E. et al. A comparison of physiological responses to percussive brain trauma in dogs and sheep. J. Neurosurg. 62, 587–591 (1985).

    Article  CAS  PubMed  Google Scholar 

  28. Hayes, R.L. et al. A new model of concussive brain injury in the cat produced by extradural fluid volume loading: II. Physiological and neuropathological observations. Brain Inj. 1, 93–112 (1987).

    Article  CAS  PubMed  Google Scholar 

  29. Pfenninger, E.G. et al. Early changes of intracranial pressure, perfusion pressure, and blood flow after acute head injury. Part 1: an experimental study of the underlying pathophysiology. J. Neurosurg. 70, 774–779 (1989).

    Article  CAS  PubMed  Google Scholar 

  30. Marmarou, A. & Shima, K. Comparative studies of edema produced by fluid percussion injury with lateral and central modes of injury in cats. Adv. Neurol. 52, 233–236 (1990).

    CAS  PubMed  Google Scholar 

  31. Thibault, L.E. et al. Biomechanical aspects of a fluid percussion model of brain injury. J. Neurotrauma 9, 311–322 (1992).

    Article  CAS  PubMed  Google Scholar 

  32. Härtl, R. et al. Early white blood cell dynamics after traumatic brain injury: effects on the cerebral microcirculation. J. Cereb. Blood Flow Metab. 17, 1210–1220 (1997).

    Article  PubMed  Google Scholar 

  33. McIntosh, T.K. et al. Traumatic brain injury in the rat: characterization of a midline fluid-percussion model. Cent. Nerv. Syst. Trauma 4, 119–134 (1987).

    Article  CAS  PubMed  Google Scholar 

  34. Dixon, C.E. et al. A fluid percussion model of experimental brain injury in the rat. J. Neurosurg. 67, 110–119 (1987).

    Article  CAS  PubMed  Google Scholar 

  35. Lindgren, S. & Rinder, L. Experimental studies in head injury. I. Some factors influencing results of model experiments. Biophysik 2, 320–329 (1965).

    CAS  PubMed  Google Scholar 

  36. Lindgren, S. & Rinder, L. Experimental studies in head injury. II. Pressure propagation in 'percussion concussion'. Biophysik 3, 174–180 (1966).

    Article  CAS  PubMed  Google Scholar 

  37. Lindgren, S. & Rinder, L. Production and distribution of intracranial and intraspinal pressure changes at sudden extradural fluid volume input in rabbits. Acta Physiol. Scand. 76, 340–351 (1969).

    Article  CAS  PubMed  Google Scholar 

  38. Sullivan, H.G. et al. Fluid-percussion model of mechanical brain injury in the cat. J. Neurosurg. 45, 520–534 (1976).

    Article  Google Scholar 

  39. McIntosh, T.K. et al. Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Neuroscience 28, 233–244 (1989).

    Article  CAS  PubMed  Google Scholar 

  40. Thompson, H.J. et al. Lateral fluid percussion brain injury: a 15-year review and evaluation. J. Neurotrauma 22, 42–75 (2005).

    Article  PubMed  Google Scholar 

  41. Morales, D.M. et al. Experimental models of traumatic brain injury: do we really need to build a better mousetrap? Neuroscience 136, 971–989 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Stalhammer, D. A new model of concussive brain injury in the cat produced by extradural fluid volume loading: I. Biomechanical properties. Brain Inj. 1, 73–91 (1987).

    Article  Google Scholar 

  43. Schmidt, R.H. & Grady, M.S. Regional patterns of blood–brain barrier breakdown following central and lateral fluid percussion injury in rodents. J. Neurotrauma 10, 415–430 (1993).

    Article  CAS  PubMed  Google Scholar 

  44. Raghupathi, R. et al. Cellular responses to traumatic brain injury. Brain Pathol. 5, 437–442 (1995).

    Article  CAS  PubMed  Google Scholar 

  45. Graham, D.I. et al. Tissue tears in the white matter after lateral fluid percussion brain injury in the rat: relevance to human brain injury. Acta Neuropathol. (Berl) 99, 117–124 (2000).

    Article  CAS  PubMed  Google Scholar 

  46. Hilton, D.L., Jr. et al. Early assessment of neurologic deficits in the fluid percussion model of brain injury. J. Neurotrauma 10, 121–133 (1993).

    Article  PubMed  Google Scholar 

  47. Hamm, R.J. et al. Selective cognitive impairment following traumatic brain injury in rats. Behav. Brain Res. 59, 169–173 (1993).

    Article  CAS  PubMed  Google Scholar 

  48. Cortez, S.C. et al. Experimental fluid percussion brain injury: vascular disruption and neuronal and glial alterations. Brain Res. 482, 271–282 (1989).

    Article  CAS  PubMed  Google Scholar 

  49. Hicks, R. et al. Temporal and spatial characterization of neuronal injury following lateral fluid-percussion brain injury in the rat. Acta Neuropathol. 91, 236–246 (1996).

    Article  CAS  PubMed  Google Scholar 

  50. Pierce, J.E. et al. Immunohistochemical characterization of alterations in the distribution of amyloid precursor proteins and beta-amyloid peptide after experimental brain injury in the rat. J. Neurosci. 16, 1083–1090 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Bramlett, H.M. & Dietrich, W.D. Quantitative structural changes in white and gray matter 1 year following traumatic brain injury in rats. Acta Neuropathol. 103, 607–614 (2002).

    Article  PubMed  Google Scholar 

  52. Vink, R. et al. Small shifts in craniotomy position in the lateral fluid percussion injury model are associated with differential lesion development. J. Neurotrauma 18, 839–847 (2001).

    Article  CAS  PubMed  Google Scholar 

  53. Graham, D.I. et al. Novel aspects of the neuropathology of the vegetative state after blunt head injury. Prog. Brain Res. 150, 445–455 (2005).

    Article  CAS  PubMed  Google Scholar 

  54. Hilton, G.D. et al. Roscovitine reduces neuronal loss, glial activation, and neurologic deficits after brain trauma. J. Cereb. Blood Flow Metab. 28, 1845–1859 (2008).

    Article  CAS  PubMed  Google Scholar 

  55. Knoblach, S.M. & Faden, A.I. Administration of either anti-intercellular adhesion molecule-1 or a nonspecific control antibody improves recovery after traumatic brain injury in the rat. J. Neurotrauma 19, 115–125 (2002).

    Article  Google Scholar 

  56. Faden, A.I. et al. Novel diketopiperazine enhances motor and cognitive recovery after traumatic brain injury in rats and shows neuroprotection in vitro and in vivo. J. Cereb. Blood Flow Metab. 23, 342–354 (2003).

    Article  CAS  PubMed  Google Scholar 

  57. Faden, A.I. Comparison of single and combination drug treatment strategies in experimental brain trauma. J. Neurotrauma 10, 91–100 (1993).

    Article  CAS  PubMed  Google Scholar 

  58. Yakovlev, A.G. et al. Activation of CPP32-like caspases contributes to neuronal apoptosis and neurological dysfunction after traumatic brain injury. J. Neurosci. 17, 7415–7424 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Di Giovanni, S. et al. Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury. Proc. Natl. Acad. Sci. USA 102, 8333–8338 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Saatman, K.E. et al. Insulin-like growth factor-I (IGF-I) improves both neurological motor and cognitive outcome following experimental brain injury. Exp. Neurol. 147, 418–427 (1997).

    Article  CAS  PubMed  Google Scholar 

  61. Pierce, J.E. et al. Enduring cognitive, neurobehavioral and histopathological changes persist for up to one year following severe experimental brain injury in rats. Neuroscience 87, 359–369 (1998).

    Article  CAS  PubMed  Google Scholar 

  62. Floyd, C.L. et al. Craniectomy position affects Morris water maze performance and hippocampal cell loss after parasagittal fluid percussion. J. Neurotrauma 19, 303–316 (2002).

    Article  PubMed  Google Scholar 

  63. Alessandri, B. et al. Cyclosporin A improves brain tissue oxygen consumption and learning/memory performance after lateral fluid percussion injury in rats. J. Neurotrauma 19, 829–841 (2002).

    Article  PubMed  Google Scholar 

  64. Liu, S. et al. Protective effect of galanin on behavioral deficits in experimental traumatic brain injury. J. Neurotrauma 11, 73–82 (2009).

    Article  Google Scholar 

  65. Saatman, K.E. et al. Calpain inhibitor AK295 attenuates motor and cognitive deficits following experimental brain injury in the rat. Proc. Natl. Acad. Sci. USA 93, 3428–3433 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Lyeth, B.G. et al. Group I metabotropic glutamate antagonist reduces acute neuronal degeneration and behavioral deficits after traumatic brain injury in rats. Exp. Neurol. 169, 191–199 (2001).

    Article  CAS  PubMed  Google Scholar 

  67. Smith, D.H. et al. Evaluation of memory dysfunction following experimental brain injury using the Morris water maze. J. Neurotrauma 8, 259–269 (1991).

    Article  CAS  PubMed  Google Scholar 

  68. Fox, G.B. et al. Sustained sensory/motor and cognitive deficits with neuronal apoptosis following controlled cortical impact brain injury in the mouse. J. Neurotrauma 15, 599–614 (1998).

    Article  CAS  PubMed  Google Scholar 

  69. Bramlett, H.M. et al. Secondary hypoxia following moderate fluid percussion brain injury in rats exacerbates sensorimotor and cognitive deficits. J. Neurotrauma 16, 1035–1047 (1999).

    Article  CAS  PubMed  Google Scholar 

  70. Loane, D.J. et al. Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. Nat. Med. 15, 377–379 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. O'Connor, C.A. et al. Interaction between anesthesia, gender, and functional outcome task following diffuse traumatic brain injury in rats. J. Neurotrauma 20, 533–541 (2003).

    Article  PubMed  Google Scholar 

  72. Hogg, S. et al. Mild traumatic lesion of the right parietal cortex in the rat: characterization of a conditioned freezing deficit and its reversal by dizocilpine. Behav. Brain Res. 93, 157–165 (1998).

    Article  CAS  PubMed  Google Scholar 

  73. Sönmez, U. et al. Neuroprotective effects of resveratrol against traumatic brain injury in immature rats. Neurosci. Lett. 420, 133–137 (2007).

    Article  PubMed  Google Scholar 

  74. Albensi, B.M. et al. Diffusion and high resolution MRI of traumatic brain injury in rats: time course and correlation with histology. Exp. Neurol. 162, 61–72 (2000).

    Article  CAS  PubMed  Google Scholar 

  75. Andrews, J.S. et al. Performance of four different rat strains in the autoshaping, two-object discrimination, and swim maze tests of learning and memory. Physiol. Behav. 57, 785–790 (1995).

    Article  CAS  PubMed  Google Scholar 

  76. Tan, A.A. et al. Strain differences in response to traumatic brain injury in Long-Evans compared to Sprague-Dawley rats. J. Neurotrauma 26, 539–548 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Avila, M.A. et al. L-arginine decreases fluid-percussion injury-induced neuronal nitrotyrosine immunoreactivity in rats. J. Cereb. Blood Flow Metab. 28, 1733–1741 (2008).

    Article  CAS  PubMed  Google Scholar 

  78. Leonard, J.R. et al. Fluid percussion injury causes disruption of the septohippocampal pathway in the rat. Exp. Neurol. 143, 177–187 (1997).

    Article  CAS  PubMed  Google Scholar 

  79. Hare, G.M.T. et al. Severe hemodilutional anemia increases cerebral tissue injury following acute neurotrauma. J. Appl. Physiol. 103, 1021–1029 (2007).

    Article  PubMed  Google Scholar 

  80. Lifshitz, J. et al. Acute cognitive improvement after lateral fluid percussion brain injury recovers by 1 month: evaluation by conditioned fear response. Behav. Brain Res. 177, 347–357 (2007).

    Article  PubMed  Google Scholar 

  81. Phillips, J.J. et al. Glutamate antagonism during secondary deafferentation enhances cognition and axo-dendritic integrity after traumatic brain injury. Hippocampus 8, 390–401 (1998).

    Article  CAS  PubMed  Google Scholar 

  82. Prins, M.L. et al. Fluid percussion brain injury in the developing and adult rat: a comparative study of mortality, morphology, intracranial pressure and mean arterial blood pressure. Brain Res. Dev. Brain Res. 95, 272–282 (1996).

    Article  CAS  PubMed  Google Scholar 

  83. Hoh, T. et al. Complex behavioral strategy and reversal learning in the water maze without NMDA receptor-dependent long-term potentiation. J. Neurosci. 19, RC2 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Vorhees, C.V. & Williams, M.T. Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat. Protoc. 1, 848–858 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was supported by the National Institutes of Health Grant no. NS052568. We would like to thank D.J. Loane for his helpful comments on the paper.

Author information

Authors and Affiliations

  1. Department of Anesthesiology and the Center for Shock, Trauma and Anesthesiology Research (STAR), School of Medicine, Baltimore, Maryland, USA

    Shruti V Kabadi, Bogdan A Stoica & Alan I Faden

  2. Department of Neuroscience, Georgetown University Medical Center, Washington, District of Columbia, USA

    Shruti V Kabadi, Genell D Hilton, Bogdan A Stoica & Alan I Faden

  3. Department of Surgery, Trauma Service, San Francisco General Hospital, San Francisco, California, USA

    Genell D Hilton

  4. Advanced Research Computing, Office of Information Services, Georgetown University, Washington, District of Columbia, USA

    David N Zapple

Authors
  1. Shruti V Kabadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Genell D Hilton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bogdan A Stoica
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. David N Zapple
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alan I Faden
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The project was conceived by A.I.F and was supported by the National Institutes of Health Grant no. NS052568 to A.I.F. The study was designed by A.I.F., B.A.S. and G.D.H. D.N.Z. originally developed the model. G.D.H. and S.V.K. equally contributed to the paper in terms of conducting the study, compiling the results and writing the paper.

Corresponding author

Correspondence to Alan I Faden.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kabadi, S., Hilton, G., Stoica, B. et al. Fluid-percussion–induced traumatic brain injury model in rats. Nat Protoc 5, 1552–1563 (2010). https://doi.org/10.1038/nprot.2010.112

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nprot.2010.112

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing