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  • Cited by 2
  • Print publication year: 2012
  • Online publication date: August 2012

10 - Animal models of mild and severe TBI: what have we learned in the past 30 years?

from Section 1 - Traumatic Brain Injury


1. Blumbergs PC , Reilly PL , Vink R . Trauma. In Love S , Louis DN , Ellison DW , eds. Greenfield's Neuropathology, 8th ed. London: Hodder Arnold; 2008. pp. 733–832.
2. McIntosh TK , Saatman KE , Raghupathi R , et al. The Dorothy Russell Memorial Lecture. The molecular and cellular sequelae of experimental traumatic brain injury: pathogenetic mechanisms. Neuropathol Appl Neurobiol 1998;24(4):251–67.
3. Vink R , Nimmo AJ . Multifunctional drugs for head injury. Neurotherapeutics 2009;6(1):28–42.
4. Ziebell JM , Morganti-Kossmann MC . Involvement of pro- and anti-inflammatory cytokines and chemokines in the pathophysiology of traumatic brain injury. Neurotherapeutics 2010;7(1):22–30.
5. Plesnila N , Schulz J , Stoffel M , et al. Role of bradykinin B2 receptors in the formation of vasogenic brain edema in rats. J Neurotrauma 2001;18(10):1049–58.
6. Loiseau H , Averet N , Arrigoni E , Cohadon F . The early phase of cryogenic lesions: an experimental model of seizures updated. Epilepsia 1987;28(3):251–8.
7. Donkin JJ , Vink R . Mechanisms of cerebral edema in traumatic brain injury: therapeutic developments. Curr Opin Neurol 2010;23:293–9.
8. Ikeda Y , Mochizuki Y , Nakamura Y , et al. Protective effect of a novel vitamin E derivative on experimental traumatic brain edema in rats – preliminary study. Acta Neurochir Suppl 2000;76:343–5.
9. Pratt J , Archambaud C , Bohme GA , et al. The effect of riluzole and mannitol on cerebral oedema after cryogenic injury in the mouse. Neurosci Lett 1999;272(3):143–5.
10. Maxwell WL , Povlishock JT , Graham DL . A mechanistic analysis of nondisruptive axonal injury: a review. J Neurotrauma 1997;14(7):419–40.
11. King CE , Rodger J , Bartlett C , et al. Erythropoietin is both neuroprotective and neuroregenerative following optic nerve transection. Exp Neurol 2007;205(1):48–55. Epub 2007 Jan 25.
12. 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(1):67–77.
13. Chen Y , Constantini S , Trembovler V , Weinstock M , Shohami E . An experimental model of closed head injury in mice: pathophysiology, histopathology, and cognitive deficits. J Neurotrauma 1996;13(10):557–68.
14. Flierl MA , Stahel PF , Beauchamp KM , et al. Mouse closed head injury model induced by a weight-drop device. Nat Protoc 2009;4(9):1328–37.
15. Masson F , Thicoipe M , Aye P , et al. Epidemiology of severe brain injuries: a prospective population-based study. J Trauma 2001;51(3):481–9.
16. Wu X , Hu J , Zhuo L , et al. Epidemiology of traumatic brain injury in eastern China, 2004: a prospective large case study. J Trauma 2008;64(5):1313–9.
17. Semple BD , Bye N , Rancan M , Ziebell JM , Morganti-Kossmann MC . Role of CCL2 (MCP-1) in traumatic brain injury (TBI): evidence from severe TBI patients and CCL2-/- mice. J Cereb Blood Flow Metab 2010;30(4):769–82.
18. McIntosh TK , Vink R , Noble L , et al. Traumatic brain injury in the rat: characterization of a lateral fluid-percussion model. Neuroscience 1989;28(1):233–44.
19. Hartl R , Medary M , Ruge M , Arfors KE , Ghajar J . Blood-brain barrier breakdown occurs early after traumatic brain injury and is not related to white blood cell adherence. Acta Neurochir Suppl 1997;70:240–2.
20. Dixon CE , Lyeth BG , Povlishock JT , et al. A fluid percussion model of experimental brain injury in the rat. J Neurosurg 1987;67(1):110–9.
21. McIntosh TK , Noble L , Andrews B , Faden AI . Traumatic brain injury in the rat: characterization of a midline fluid-percussion model. CNS Trauma 1987;4:119–34.
22. Vink R , McIntosh TK , Weiner MW , Faden AI . Effects of traumatic brain injury on cerebral high-energy phosphates and pH: a 31P magnetic resonance spectroscopy study. J Cereb Blood Flow Metab 1987;7(5):563–71.
23. Vink R , Mullins PG , Temple MD , Bao W , Faden AI . Small shifts in craniotomy position in the lateral fluid percussion injury model are associated with differential lesion development. J Neurotrauma 2001;18(8):839–47.
24. Floyd CL , Golden KM , Black RT , Hamm RJ , Lyeth BG . Craniectomy position affects morris water maze performance and hippocampal cell loss after parasagittal fluid percussion. J Neurotrauma 2002;19(3):303–16.
25. Kabadi SV , Hilton GD , Stoica BA , Zapple DN , Faden AI . Fluid-percussion-induced traumatic brain injury model in rats. Nat Protoc 2010;5(9):1552–63.
26. Thompson HJ , Lifshitz J , Marklund N , et al. Lateral fluid percussion brain injury: a 15-year review and evaluation. J Neurotrauma 2005;22(1):42–75.
27. Lyeth BG , Jenkins LW , Hamm RJ , et al. Prolonged memory impairment in the absence of hippocampal cell death following traumatic brain injury in the rat. Brain Res 1990;526(2):249–58.
28. Yamaki T , Murakami N , Iwamoto Y , et al. Cognitive dysfunction and histological findings in rats with chronic-stage contusion and diffuse axonal injury. Brain Res Protoc 1998;3(1):100–6.
29. 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(2):187–96.
30. Hayes RL , Stalhammar D , Povlishock JT , et al. A new model of concussive brain injury in the cat produced by extradural fluid volume loading: II. Physiological and neuropathological observations. Brain Injury 1987;1(1):93–112.
31. Suzuki T , Bramlett HM , Dietrich WD . The importance of gender on the beneficial effects of posttraumatic hypothermia. Exp Neurol 2003;184(2):1017–26.
32. Lighthall JW . Controlled cortical impact: a new experimental brain injury model. J Neurotrauma 1988;5(1):1–15.
33. Dixon CE , Clifton GL , Lighthall JW , Yaghmai AA , Hayes RL . A controlled cortical impact model of traumatic brain injury in the rat. J Neurosci Methods 1991;39(3):253–62.
34. Hannay HJ , Feldman Z , Phan P , et al. Validation of a controlled cortical impact model of head injury in mice. J Neurotrauma 1999;16(11):1103–14.
35. Manley GT , Rosenthal G , Lam M , et al. Controlled cortical impact in swine: pathophysiology and biomechanics. J Neurotrauma 2006;23(2):128–39.
36. Goodman JC , Cherian L , Bryan RM , Jr., Robertson CS. Lateral cortical impact injury in rats: pathologic effects of varying cortical compression and impact velocity. J Neurotrauma 1994;11(5):587–97.
37. Chauhan NB , Gatto R , Chauhan MB . Neuroanatomical correlation of behavioral deficits in the CCI model of TBI. J Neurosci Methods 2010;190(1):1–9.
38. Marmarou A , Foda MA , van den Brink W , et al. A new model of diffuse brain injury in rats. Part I: pathophysiology and biomechanics. J Neurosurg 1994;80(2):291–300.
39. Foda MA , Marmarou A . A new model of diffuse brain injury in rats. Part II: morphological characterization. J Neurosurg 1994;80(2):301–13.
40. Povlishock JT , Marmarou A , McIntosh TK , Trojanowski JQ , Moroi J . Impact acceleration injury in the rat – evidence for focal axolemmal change and related neurofilament sidearm alteration. J Neuropath Exp Neurol 1997;56:347–59.
41. Beaumont A , Marmarou A , Czigner A , et al. The impact-acceleration model of head injury: injury severity predicts motor and cognitive performance after trauma. Neurol Res 1999;21(8):742–54.
42. Donkin JJ , Nimmo AJ , Cernak I , Blumbergs PC , Vink R . Substance P is associated with the development of brain edema and functional deficits after traumatic brain injury. J Cereb Blood Flow Metab 2009;29(8):1388–98.
43. Hans VH , Kossmann T , Lenzlinger PM , et al. Experimental axonal injury triggers interleukin-6 mRNA, protein synthesis and release into cerebrospinal fluid. J Cereb Blood Flow Metab 1999;19(2):184–94.
44. Rancan M , Otto VI , Hans VH , et al. Upregulation of ICAM-1 and MCP-1 but not of MIP-2 and sensorimotor deficit in response to traumatic axonal injury in rats. J Neurosci Res 2001;63(5):438–46.
45. Stahel PF , Kossmann T , Morganti-Kossmann MC , Hans VH , Barnum SR . Experimental diffuse axonal injury induces enhanced neuronal C5a receptor mRNA expression in rats. Brain Res Mol Brain Res 1997;50(1–2):205–12.
46. Hellewell SC , Yan EB , Agyapomaa DA , Bye N , Morganti-Kossmann MC . Post-traumatic hypoxia exacerbates brain tissue damage: analysis of axonal injury and glial responses. J Neurotrauma 2010;27(11):1997–2010.
47. Heath DL , Vink R . Impact acceleration-induced severe diffuse axonal injury in rats: characterization of phosphate metabolism and neurologic outcome. J Neurotrauma 1995;12(6):1027–34.
48. Stibick DL , Feeney DM . Enduring vulnerability to transient reinstatement of hemiplegia by prazosin after traumatic brain injury. J Neurotrauma 2001;18(3):303–12.
49. O’Connor C , Heath DL , Cernak I , Nimmo AJ , Vink R . Effects of daily versus weekly testing and pre-training on the assessment of neurologic impairment following diffuse traumatic brain injury in rats. J Neurotrauma 2003;20(10):985–93.
50. Cernak I , Chang T , Ahmed FA , et al. Pathophysiological response to experimental diffuse brain trauma differs as a function of developmental age. Dev Neurosci 2010;32(5–6):442–53.
51. Brodhun M , Fritz H , Walter B , et al. Immunomorphological sequelae of severe brain injury induced by fluid-percussion in juvenile pigs–effects of mild hypothermia. Acta Neuropathol 2001;101(5):424–34.
52. Solomon D , Kim B , Scultetus A , et al. The effect of rFVIIa on pro- and anti-inflammatory cytokines in serum and cerebrospinal fluid in a swine model of traumatic brain injury. Cytokine 2011;54(1):20–3.
53. Duhaime AC , Margulies SS , Durham SR , et al. Maturation-dependent response of the piglet brain to scaled cortical impact. J Neurosurg 2000;93(3):455–62.
54. Lewis SB , Finnie JW , Blumbergs PC , et al. A head impact model of early axonal injury in the sheep. J Neurotrauma 1996;13(9):505–14.
55. Anderson RW , Brown CJ , Blumbergs PC , McLean AJ , Jones NR . Impact mechanics and axonal injury in a sheep model. J Neurotrauma 2003;20(10):961–74.
56. Van Den Heuvel C , Donkin JJ , Finnie JW , et al. Downregulation of amyloid precursor protein (APP) expression following post-traumatic cyclosporin-A administration. J Neurotrauma 2004;21(11):1562–72.
57. Finnie JW , Manavis J , Summersides GE , Blumbergs PC . Brain damage in pigs produced by impact with a non-penetrating captive bolt pistol. Aust Vet J 2003;81(3):153–5.
58. Vink R , Bhatia KD , Reilly PL . The relationship between intracranial pressure and brain oxygenation following traumatic brain injury in sheep. Acta Neurochir Suppl 2008;102:189–92.
59. Gennarelli TA , Thibault LE , Adams JH , et al. Diffuse axonal injury and traumatic coma in the primate. Ann Neurol 1982;12(6):564–74.
60. Ross DT , Meaney DF , Sabol MK , Smith DH , Gennarelli TA . Distribution of forebrain diffuse axonal injury following inertial closed head injury in miniature swine. Exp Neurol 1994;126(2):291–9.
61. Smith DH , Chen XH , Xu BN , et al. Characterization of diffuse axonal pathology and selective hippocampal damage following inertial brain trauma in the pig. J Neuropathol Exp Neurol 1997;56(7):822–34.
62. Krave U , Al-Olama M , Hansson HA . Rotational acceleration closed head flexion trauma generates more extensive diffuse brain injury than extension. J Neurotrauma 2011;28:57–70.
63. Maxwell WL , Watt C , Graham DI , Gennarelli TA . Ultrastructural evidence of axonal shearing as a result of lateral acceleration of the head in non-human primates. Acta Neuropathol 1993;86(2):136–44.
64. Gabrielian L , Willshire L , Helps S , et al. Intracranial pressure changes following traumatic brain injury in rats: lack of significant change in the absence of mass lesions or hypoxia. J Neurotrauma 2011;28(10):2103–11.