Brain Neurorehabil.  2011 Mar;4(1):12-20. 10.12786/bn.2011.4.1.12.

Animal Models of Traumatic Brain Injury

  • 1Department of Rehabilitation Medicine, Konkuk University Medical Center & School of Medicine, Konkuk University, Korea.


Traumatic brain injury could be used to describe all injuries to the brain caused by external mechanical forces. It shows a variety of clinical manifestations from mild to severe forms and can result to death. Moderate to severe injuries can produce disabilities on physical, cognitive, behavioral, and emotional aspects. Animal models of traumatic brain injury have been developed to reproduce characteristics of human brain injury, to understand molecular and cellular pathophysiology and neurobehavioral outcomes following trauma and to find out the promising pharmacological drugs or rehabilitative skills to treat. This article reviewed the current experimental traumatic brain injury models, including weight drop, fluid percussion, and controlled cortical impact, and also the neurobehavioral assessments that are most commonly used to measure loss of function.


injury model; neurobehavioral assessment; traumatic brain injury

MeSH Terms

Brain Injuries
Models, Animal


1. Whyte J, Ponsford J, Watanabe T, Hart T. Gans BM, Walsh NE, Robinson LR, editors. Traumatic brain injury. DeLisa's Physical Medicine & Rehabilitation: principles and practice. 2011. Phildelphia: Lippincott Williams & Wilkins;575–623.
2. Macciocchi SN, Reid DB, Barth JT. Disability following head injury. Curr Opin Neurol. 1993. 6:773–777.
3. Povlishock JT, Hayes RL, Michel ME, McIntosh TK. Workshop on animal models of traumatic brain injury. J Neurotrauma. 1994. 11:723–732.
4. Graham DI, Gennarelli TA, McIntosh TK. Graham DI, Lantos PL, editors. Cellular and molecular consequences of TBI. Greenfield's neuropathology. 2002. New York: Hodder Arnold Publication;823–898.
5. Stålhammar D. Experimental models of head injury. Acta Neurochir Suppl (Wien). 1986. 36:33–46.
6. Morales DM, Marklund N, Lebold D, Thompson HJ, Pitkanen A, Maxwell WL, Longhi L, Laurer H, Maegele M, Neugebauer E, Graham DI, Stocchetti N, McIntosh TK. Experimental models of traumatic brain injury: do we really need to build a better mousetrap. Neuroscience. 2005. 136:971–989.
7. Povlishock JT, Katz DI. Update of neuropathology and neurological recovery after traumatic brain injury. J Head Trauma Rehabil. 2005. 20:76–94.
8. Graham DI, McIntosh TK, Maxwell WL, Nicoll JA. Recent advances in neurotrauma. J Neuropathol Exp Neurol. 2000. 59:641–651.
9. Gennarelli TA. Animate models of human head injury. J Neurotrauma. 1994. 11:357–368.
10. McIntosh TK, Saatman KE, Raghupathi R, Graham DI, Smith DH, Lee VM, Trojanowski JQ. The Dorothy Russell Memorial Lecture. The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms. Neuropathol Appl Neurobiol. 1998. 24:251–267.
11. Marmarou A, Foda MA, van den Brink W, Campbell J, Kita H, Demetriadou K. A new model of diffuse brain injury in rats. Part I: Pathophysiology and biomechanics. J Neurosurg. 1994. 80:291–300.
12. Adelson PD, Robichaud P, Hamilton RL, Kochanek PM. A model of diffuse traumatic brain injury in the immature rat. J Neurosurg. 1996. 85:877–884.
13. Adelson PD, Dixon CE, Kochanek PM. Long-term dysfunction following diffuse traumatic brain injury in the immature rat. J Neurotrauma. 2000. 17:273–282.
14. Feeney DM, Boyeson MG, Linn RT, Murray HM, Dail WG. Responses to cortical injury: I. Methodology and local effects of contusions in the rat. Brain Res. 1981. 211:67–77.
15. Lighthall JW. Controlled cortical impact: a new experimental brain injury model. J Neurotrauma. 1988. 5:1–15.
16. Pullela R, Raber J, Pfankuch T, Ferriero DM, Claus CP, Koh SE, Yamauchi T, Rola R, Fike JR, Noble-Haeusslein LJ. Traumatic injury to the immature brain results in progressive neuronal loss, hyperactivity and delayed cognitive impairments. Dev Neurosci. 2006. 28:396–409.
17. Lindgren S, Rinder L. Experimental studies in head injury. I. Some factors influencing results of model experiments. Biophysik. 1965. 2:320–329.
18. Stalhammar DA. Vinken PJ, Bruyn GW, Klawans HL, Braakman R, editors. The mechanisms of brain injuries. Head Injury Handbook of Clinical Neurology, Vol. 57. 1990. Amsterdam: Elsevier Science;17–41.
19. Smith DH, Chen XH, Pierce JE, Wolf JA, Trojanowski JQ, Graham DI, McIntosh TK. Progressive atrophy and neuron death for one year following brain trauma in the rat. J Neurotrauma. 1997. 14:715–727.
20. Saatman KE, Graham DI, McIntosh TK. The neuronal cytoskeleton is at risk after mild and moderate brain injury. J Neurotrauma. 1998. 15:1047–1058.
21. Muir JK, Boerschel M, Ellis EF. Continuous monitoring of posttraumatic cerebral blood flow using laser-Doppler flowmetry. J Neurotrauma. 1992. 9:355–362.
22. Thompson HJ, Lifshitz J, Marklund N, Grady MS, Graham DI, Hovda DA, McIntosh TK. Lateral fluid percussion brain injury: a 15-year review and evaluation. J Neurotrauma. 2005. 22:42–75.
23. Maxwell WL, Graham DI. Loss of axonal microtubules and neurofilaments after stretch-injury to guinea pig optic nerve fibers. J Neurotrauma. 1997. 14:603–614.
24. Gennarelli TA, Thibault LE, Tipperman R, Tomei G, Sergot R, Brown M, Maxwell WL, Graham DI, Adams JH, Irvine A, Gennarelli LM, Duhaime AC, Boock R, Greenberg J. Axonal injury in the optic nerve: a model simulating diffuse axonal injury in the brain. J Neurosurg. 1989. 71:244–253.
25. Saatman KE, Abai B, Grosvenor A, Vorwerk CK, Smith DH, Meaney DF. Traumatic axonal injury results in biphasic calpain activation and retrograde transport impairment in mice. J Cereb Blood Flow Metab. 2003. 23:34–42.
26. Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR. Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology. 1989. 15:49–59.
27. Laurer HL, McIntosh TK. Experimental models of brain trauma. Curr Opin Neurol. 1999. 12:715–721.
28. Concensus conference. Rehabiltation of persons with traumatic brain injury. NIH Concensus Developmental Panel on rehabilitation of persons with traumatic brain injury. JAMA. 1999. 282:974–983.
29. Kacew S, Dixit R, Ruben Z. Diet and rat strain as factors in nervous system function and influence of confounders. Biomed Environ Sci. 1998. 11:203–217.
30. Voikar V, Koks S, Vasar E, Rauvala H. Strain and gender differences in the behavior of mouse lines commonly used in trasgenic studies. Physiol Behav. 2001. 72:271–281.
31. Steward O, Schauwecker PE, Guth L, Zhang Z, Fujiki M, Inman D, Wrathall J, Kempermann G, Gage FH, Saatman KE, Raghupathi R, McIntosh T. Genetic approaches to neurotrauma research: opportunities and pitfalls of murine models. Exp Neurol. 1999. 15:19–42.
32. Roof RL, Stein DG. Gender differences in Morris water maze performance depend on task parameters. Physiol Behav. 1999. 68:81–86.
33. Boyeson MG, Jones JL, Harmon RL. Sparing of motor function after cortical injury: a new perspective on underlying mechanisms. Arch Neurol. 1994. 51:405–414.
34. Skelton RW. Modeling recovery of cognitive function after traumatic brain injury: spatial navigation in the Morris water maze after complete or partial transections of the perforant path in rats. Behav Brain Res. 1998. 96:13–35.
35. Kokiko ON, Hamm RJ. A review of pharmacological treatments used in experimental models of traumatic brain injury. Brain Inj. 2007. 21:259–274.
36. Shohami E, Novikov M, Bass R. Long-term effect of HU-211, a novel non-competitive NMDA antagonist, on motor and memory functions after closed head injury in the rat. Brain Res. 1995. 674:55–62.
37. Dixon CE, Lyeth BG, Povlishock JT, Findling R, Hamm R, Marmarou A, Young HF, Hayes RL. A fluid percussion model of experimental brain injury in the rat: neurological, physiological, and histopathological dharacteristics. J Neurosurg. 1987. 67:110–119.
38. Hamm RJ, Pike BR, O'Dell DM, Lyeth BG, Jenkins LW. The rotarod test: an evaluation of its effectiveness in assessing motor deficits following traumatic brain injury. J Neurotrauma. 1994. 11:187–196.
39. Baskin YK, Dietrich WD, Green EJ. Two effective behavioral tasks for evaluating sensorimotor dysfunction following traumatic brain injury in mice. J Neurosci Methods. 2003. 129:87–93.
40. Mattiasson GJ, Philips MF, Tomasevic G, Johansson BB, Wieloch T, McIntosh TK. The rotating pole test: evaluation of its effectiveness in assessing functional motor deficits following experimental brain injury in rat. J Neurosci Methods. 2000. 95:75–82.
41. Hemandez TD, Schallert T. Seizures and recovery from experimental brain damage. Exp Neurol. 1988. 102:318–324.
42. Eccles JC. Mechanisms of long-term memory. J Physiol (Paris). 1986. 81:312–317.
43. Kobayashi Y, Isa T. Sensory-motor gating and cognitive control by the brainstem cholinergic system. Neural Netw. 2002. 15:731–741.
44. Leonard JR, Maris DO, Grady MS. Fluid percussion injury causes loss of forebrain choline acetyltransferase and nerve growth factor receptor immunoreactive cells in the rat. J Neurotrauma. 1994. 11:379–392.
45. Pike BR, Hamm RJ. Activating the posttraumatic cholinergic system for the treatment of cognitive impairment following traumatic brain injury. Pharmacol Biochem Behav. 1997. 57:785–791.
46. Sanders MJ, Dietrich WD, Green EJ. Cognitive function following traumatic brain injury: effects of injury severity and recovery period in a parasagittal fluid-percussive injury model. J Neurotrauma. 1999. 16:915–925.
47. Lyeth BG, Jenkins LW, Hamm RJ, Dixon CE, Phillips LL, Clifton GL, Young HF, Hayes RL. Prolonged memory impairment in the absence of hippocampal cell death following traumatic brain injury in the rat. Brain Res. 1990. 526:249–258.
48. Piot-Grosjean O, Wahl F, Gobbo O, Stutzmann JM. Assessment of sensorimotor and cognitive deficits induced by a moderate traumatic injury in the right parietal cortex of the rat. Neurobiol Dis. 2001. 8:1082–1093.
49. Yamaguchi T, Ozawa Y, Suzuki M, Yamamoto M, Nakamura T, Yamaura A. Indeloxazine hydrochloride improves impairment of passive avoidance performance after fluid percussion brain injury in rats. Neuropharmacology. 1996. 35:329–336.
50. Hamm RJ, Lyeth BG, Jenkins LW, ODell DM, Pike BR. Selective cognitive impairment following traumatic brain injury in rats. Behav Brain Res. 1993. 59:169–173.
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